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Background: Lithospermeae is the largest tribe within Boraginaceae. The tribe has been the focus of multiple phylogenetic studies over the last 15 years, with most focused on one genus or a few genera. In the present study, we newly sequenced 69 species of Lithospermeae and relatives to analyze the phylogenomic relationships among its members as well as the evolution of the plastid genome. Results: The phylogeny of Lithospermeae resolved from the plastid genome and nrDNA cistron is generally congruent with prior studies, but is better resolved and supported. Increasing character sampling across the plastid genome results in gradually more similar trees to that from the entire plastid genome. Overall, plastid genome structure was quite consistent across Lithospermeae. Codon Usage Bias (CUB) analyses demonstrate that across Lithospermeae plastid genomes were rich in AT and poor in GC. Mutation may play a greater role than selection across the plastid genome of Lithospermeae. The present study is the first to highlight the CUB characteristics of Lithospermeae species, which can help elucidate the mechanisms underlying patterns of molecular evolution and improve the expression levels of exogenous genes by codon optimization. Conclusions: This study provides a comprehensive phylogenomic analysis of Lithospermeae, significantly enhancing our understanding of the phylogenetic relationships and plastid genome evolution within this largest tribe of Boraginaceae. By utilizing an expanded genomic sampling approach, we have achieved increased resolution and support among the evolutionary relationships of the tribe, in line with but improving upon previous studies. The analyses of plastid genome structure revealed consistency across Lithospermeae, with a notable CUB. This study marks the first investigation into the CUB of Lithospermeae species and sets the stage for further research on the molecular evolution of plastid genomes across Boraginaceae. [ABSTRACT FROM AUTHOR]

The Halimedineae are marine green macroalgae that play crucial roles as primary producers in various habitats, including coral reefs, rocky shores, embayments, lagoons, and seagrass beds. Several tropical species have calcified thalli, which contribute significantly to the formation of coral reefs. In this study, we investigated the codon usage patterns and the main factors influencing codon usage bias in 16 chloroplast genomes of the suborder Halimedineae. Nucleotide composition analysis revealed that the codons of these species were enriched in A/U bases and preferred to end in A/U bases, and the distribution of GC content followed a trend of GC1 > GC2 > GC3. 30 optimal codons encoding 17 amino acids were identified, and most of the optimal codons and all of the over-expressed codons preferentially ended with A/U. The neutrality plot, effective number of codons (ENc) plot, and parity rule 2 (PR2) plot analysis indicated that natural selection played a major role in shaping codon usage bias of the most Halimedineae species. The genetic relationships based on their RSCU values and chloroplast protein-coding genes showed the closely related species have similar codon usage patterns. This study describes, for the first time, the codon usage patterns and characterization of Halimedineae chloroplast genomes, and provides new insights into the evolution of this suborder. [ABSTRACT FROM AUTHOR]

Background: The tribe Ampelopsideae plants are important garden plants with both medicinal and ornamental values. The study of codon usage bias (CUB) facilitates a deeper comprehension of the molecular genetic evolution of species and their adaptive strategies. The joint analysis of CUB in chloroplast genomes (cpDNA) offers valuable insights for in-depth research on molecular genetic evolution, biological resource conservation, and elite breeding within this plant family. Results: The base composition and codon usage preferences of the eighteen chloroplast genomes were highly similar, with the GC content of bases at all positions of their codons being less than 50%. This indicates that they preferred A/T bases. Their effective codon numbers were all in the range of 35–61, which indicates that the codon preferences of the chloroplast genomes of the 18 Ampelopsideae plants were relatively weak. A series of analyses indicated that the codon preference of the chloroplast genomes of the 18 Ampelopsideae plants was influenced by a combination of multiple factors, with natural selection being the primary influence. The clustering tree generated based on the relative usage of synonymous codons is consistent with some of the results obtained from the phylogenetic tree of chloroplast genomes, which indicates that the clustering tree based on the relative usage of synonymous codons can be an important supplement to the results of the sequence-based phylogenetic analysis. Eventually, 10 shared best codons were screened on the basis of the chloroplast genomes of 18 species. Conclusion: The codon preferences of the chloroplast genome in Ampelopsideae plants are relatively weak and are primarily influenced by natural selection. The codon composition of the chloroplast genomes of the eighteen Ampelopsideae plants and their usage preferences were sufficiently similar to demonstrate that the chloroplast genomes of Ampelopsideae plants are highly conserved. This study provides a scientific basis for the genetic evolution of chloroplast genes in Ampelopsideae species and their suitable strategies. [ABSTRACT FROM AUTHOR]

Background: The invasive pest Spotted-Wing Drosophila, Drosophila suzukii (Matsumura), causes extensive damage and production losses of soft-skinned fruits. Native to Asia, the species has now spread worldwide, with first reports in Portugal in 2012. In this study, we focus on the genomic signatures of the recent Portuguese invasion, in the context of worldwide patterns established in previous works. We analyzed whole genome pool sequencing data from three Portuguese populations (N = 240) sampled in 2019 and 2021. Results: The correlation of allele frequencies suggested that Portuguese populations are related to South European ones, indicating a Mediterranean invasion route. While two populations exhibited levels of genetic variation comparable to others in the invasive range, a third showed low levels of genetic diversity, which may result from a recent colonization of the region. Genome-wide analyses of natural selection identified ten genes previously associated with D. suzukii's invasive capacity, which may have contributed to the species' success in Portugal. Additionally, we pinpointed six genes evolving under positive selection across Portuguese populations but not in European ones, which is indicative of local adaptation. One of these genes, nAChRalpha7, encodes a nicotinic acetylcholine receptor, which are known targets for insecticides widely used for D. suzukii control, such as neonicotinoids and spinosyns. Although spinosyn resistance has been associated with mutations in the nAChRalpha6 in other Drosophila species, the putative role of nAChRalpha7 in insecticide resistance and local adaptation in Portuguese D. suzukii populations encourages future investigation. Conclusions: Our results highlight the complex nature of rapid species invasions and the role of rapid local adaptation in determining the invasive capacity of these species. [ABSTRACT FROM AUTHOR]

Background: The recombination landscape and subsequent natural selection have vast consequences forevolution and speciation. However, most of the crossover and recombination hotspots are yet to be discovered. We previously reported the relevance of C and G trinucleotide two-repeat units (CG-TTUs) in crossovers and recombination. Methods: On a genome-wide scale, here we mapped all combinations of A and T trinucleotide two-repeat units (AT-TTUs) in human, consisting of AATAAT, ATAATA, ATTATT, TTATTA, TATTAT, and TAATAA. We also compared a number of the colonies formed by the AT-TTUs (distance between consecutive AT-TTUs < 500 bp) in several other primates and mouse. Results: We found that the majority of the AT-TTUs (> 96%) resided in approximately 1.4 million colonies, spread throughout the human genome. In comparison to the CG-TTU colonies, the AT-TTU colonies were significantly more abundant and larger in size. Pure units and overlapping units of the pure units were readily detectable in the same colonies, signifying that the units were the sites of unequal crossover. We discovered dynamic sharedness of several of the colonies across the primate species studied, which mainly reached maximum complexity and size in human. Conclusions: We report novel crossover and recombination hotspots of the finest molecular resolution, massively spread and shared across the genomes of human and several other primates. With respect to crossovers and recombination, these genomes are far more dynamic than previously envisioned. [ABSTRACT FROM AUTHOR]

Background: Adaptation to cold was essential for human migration across Eurasia. Non-shivering thermogenesis through brown adipose tissue (BAT) participates in cold adaptation because some genes involved in the differentiation and function of BAT exhibit signatures of positive natural selection in populations at high latitudes. Whether these genes are associated with the inter-individual variability in BAT thermogenesis remains unclear. In this study, we evaluated the potential associations between BAT activity and single nucleotide polymorphisms (SNPs) in candidate gene regions in East Asian populations. Methods: BAT activity induced by mild cold exposure was measured in 399 healthy Japanese men and women using fluorodeoxyglucose-positron emission tomography and computed tomography (FDG-PET/CT). The capacity for cold-induced thermogenesis and fat oxidation was measured in 56 men. Association analyses with physiological traits were performed for 11 SNPs at six loci (LEPR, ANGPTL8, PLA2G2A, PLIN1, TBX15-WARS2, and FADS1) reported to be under positive natural selection. Associations found in the FDG-PET/CT population were further validated in 84 healthy East Asian men and women, in whom BAT activity was measured using infrared thermography. Associations between the SNP genotypes and BAT activity or other related traits were tested using multiple logistic and linear regression models. Results: Of the 11 putative adaptive alleles of the six genes, two intronic SNPs in LEPR (rs1022981 and rs12405556) tended to be associated with higher BAT activity. However, these did not survive multiple test comparisons. Associations with lower body fat percentage, plasma triglyceride, insulin, and HOMA-IR levels were observed in the FDG-PET/CT population (P < 0.05). Other loci, including TBX15-WARS2, which is speculated to mediate cold adaptation in Greenland Inuits, did not show significant differences in BAT thermogenesis. Conclusions: Our results suggest a marginal but significant association between LEPR SNPs. However, robust supporting evidence was not established for the involvement of other loci under positive natural selection in cold adaptation through BAT thermogenesis in East Asian adults. Given the pleiotropic function of these genes, factors other than cold adaptation through BAT thermogenesis, such as diet adaptation, may contribute to positive natural selection at these loci. [ABSTRACT FROM AUTHOR]

Background: Managing genetic diversity is critically important for maintaining species fitness. Excessive homozygosity caused by the loss of genetic diversity can have detrimental effects on the reproduction and production performance of a breed. Analysis of genetic diversity can facilitate the identification of signatures of selection which may contribute to the specific characteristics regarding the health, production and physical appearance of a breed or population. In this study, breeds with well-characterized traits such as fine wool production (Rambouillet, N = 745), parasite resistance (Katahdin, N = 581) and environmental hardiness (Dorper, N = 265) were evaluated for inbreeding, effective population size (Ne), runs of homozygosity (ROH) and Wright's fixation index (FST) outlier approach to identify differential signatures of selection at 36,113 autosomal single nucleotide polymorphisms (SNPs). Results: Katahdin sheep had the largest current Ne at the most recent generation estimated with both the GONe and NeEstimator software. The most highly conserved ROH Island was identified in Rambouillet with a signature of selection on chromosome 6 containing 202 SNPs called in an ROH in 50 to 94% of the individuals. This region contained the DCAF16, LCORL and NCAPG genes that have been previously reported to be under selection and have biological roles related to milk production and growth traits. The outlier regions identified through the FST comparisons of Katahdin with Rambouillet and Dorper contained genes with known roles in milk production and mastitis resistance or susceptibility, and the FST comparisons of Rambouillet with Katahdin and Dorper identified genes related to wool growth, suggesting these traits have been under natural or artificial selection pressure in these populations. Genes involved in the cytokine-cytokine receptor interaction pathways were identified in all FST breed comparisons, which indicates the presence of allelic diversity between these breeds in genomic regions controlling cytokine signaling mechanisms. Conclusions: In this paper, we describe signatures of selection within diverse and economically important U.S. sheep breeds. The genes contained within these signatures are proposed for further study to understand their relevance to biological traits and improve understanding of breed diversity. [ABSTRACT FROM AUTHOR]

Background: Inner Mongolia cashmere goat (IMCG), renowned for its superior cashmere quality, is a Chinese indigenous goat breed that has been developed through natural and artificial selection over a long period. However, recently, the genetic resources of IMCGs have been significantly threatened by the introduction of cosmopolitan goat breeds and the absence of adequate breed protection systems. Results: In order to assess the conservation effectiveness of IMCGs and efficiently preserve and utilize the purebred germplasm resources, this study analyzed the genetic diversity, kinship, family structure, and inbreeding of IMCGs utilizing resequencing data from 225 randomly selected individuals analyzed using the Plink (v.1.90), GCTA (v.1.94.1), and R (v.4.2.1) software. A total of 12,700,178 high-quality SNPs were selected through quality control from 34,248,064 SNP sites obtained from 225 individuals. The average minor allele frequency (MAF), polymorphic information content (PIC), and Shannon information index (SHI) were 0.253, 0.284, and 0.530, respectively. The average observed heterozygosity (Ho) and the average expected heterozygosity (He) were 0.355 and 0.351, respectively. The analysis of the identity by state distance matrix and genomic relationship matrix has shown that most individuals' genetic distance and genetic relationship are far away, and the inbreeding coefficient is low. The family structure analysis identified 10 families among the 23 rams. A total of 14,109 runs of homozygosity (ROH) were identified in the 225 individuals, with an average ROH length of 1014.547 kb. The average inbreeding coefficient, calculated from ROH, was 0.026 for the overall population and 0.027 specifically among the 23 rams, indicating a low level of inbreeding within the conserved population. Conclusions: The IMCGs exhibited moderate polymorphism and a low level of kinship with inbreeding occurring among a limited number of individuals. Simultaneously, it is necessary to prevent the loss of bloodline to guarantee the perpetuation of the IMCGs' germplasm resources. [ABSTRACT FROM AUTHOR]

Background: Long-term natural and artificial selection has resulted in many genetic footprints within the genomes of pig breeds across distinct agroecological zones. Nevertheless, the mechanisms by which these signatures contribute to phenotypic diversity and facilitate environmental adaptation remain unclear. Results: Here, we leveraged whole-genome sequencing data from 82 individuals from 6 domestic pig breeds originating in tropical, high-altitude, and frigid regions. Population genetic analysis suggested that habitat isolation significantly shaped the genetic diversity and contributed to population stratification in local Chinese pig breeds. Analysis of selection signals revealed regions under selection for adaptation in tropical (55.5 Mb), high-altitude (43.6 Mb), and frigid (17.72 Mb) regions. The potential functions of the selective sweep regions were linked to certain complex traits that might play critical roles in different geographic environments, including fat coverage in frigid environments and blood indicators in tropical and high-altitude environments. Candidate genes under selection were significantly enriched in biological pathways involved in environmental adaptation. These pathways included blood circulation, protein degradation, and inflammation for adaptation to tropical environments; heart and lung development, hypoxia response, and DNA damage repair for high-altitude adaptation; and thermogenesis, cold-induced vasodilation (CIVD), and the cell cycle for adaptation to frigid environments. By examining the chromatin state of the selection signatures, we identified the lung and ileum as two candidate functional tissues for environmental adaptation. Finally, we identified a mutation (chr1: G246,175,129A) in the cis-regulatory region of ABCA1 as a plausible promising variant for adaptation to tropical environments. Conclusions: In this study, we conducted a genome-wide exploration of the genetic mechanisms underlying the adaptability of local Chinese pig breeds to tropical, high-altitude, and frigid environments. Our findings shed light on the prominent role of cis-regulatory elements in environmental adaptation in pigs and may serve as a valuable biological model of human plateau-related disorders and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Background: Oil bodies or lipid droplets (LDs) in the cytosol are the subcellular storage compartments of seeds and the sites of lipid metabolism providing energy to the germinating seeds. Major LD-associated proteins are lipoxygenases, phospholipaseD, oleosins, TAG-lipases, steroleosins, caleosins and SEIPINs; involved in facilitating germination and enhancing peroxidation resulting in off-flavours. However, how natural selection is balancing contradictory processes in lipid-rich seeds remains evasive. The present study was aimed at the prediction of selection signatures among orthologous clades in major oilseeds and the correlation of selection effect with gene expression. Results: The LD-associated genes from the major oil-bearing crops were analyzed to predict natural selection signatures in phylogenetically close-knit ortholog clusters to understand adaptive evolution. Positive selection was the major force driving the evolution and diversification of orthologs in a lineage-specific manner. Significant positive selection effects were found in 94 genes particularly in oleosin and TAG-lipases, purifying with excess of non-synonymous substitution in 44 genes while 35 genes were neutral to selection effects. No significant selection impact was noticed in Brassicaceae as against LOX genes of oil palm. A heavy load of deleterious mutations affecting selection signatures was detected in T-lineage oleosins and LOX genes of Arachis hypogaea. The T-lineage oleosin genes were involved in mainly anther, tapetum and anther wall morphogenesis. In Ricinus communis and Sesamum indicum > 85% of PLD genes were under selection whereas selection pressures were low in Brassica juncea and Helianthus annuus. Steroleosin, caleosin and SEIPINs with large roles in lipid droplet organization expressed mostly in seeds and were under considerable positive selection pressures. Expression divergence was evident among paralogs and homeologs with one gene attaining functional superiority compared to the other. The LOX gene Glyma.13g347500 associated with off-flavor was not expressed during germination, rather its paralog Glyma.13g347600 showed expression in Glycine max. PLD-α genes were expressed on all the tissues except the seed,δ genes in seed and meristem while β and γ genes expressed in the leaf. Conclusions: The genes involved in seed germination and lipid metabolism were under strong positive selection, although species differences were discernable. The present study identifies suitable candidate genes enhancing seed oil content and germination wherein directional selection can become more fruitful. [ABSTRACT FROM AUTHOR]

Background: Ancient northern East Asians (ANEA) from the Yellow River region, who pioneered millet cultivation, play a crucial role in understanding the origins of ethnolinguistically diverse populations in modern China and the entire landscape of deep genetic structure and variation discovery in modern East Asians. However, the direct links between ANEA and geographically proximate modern populations, as well as the biological adaptive processes involved, remain poorly understood. Results: Here, we generated genome-wide SNP data for 264 individuals from geographically different Han populations in Shandong. An integrated genomic resource encompassing both modern and ancient East Asians was compiled to examine fine-scale population admixture scenarios and adaptive traits. The reconstruction of demographic history and hierarchical clustering patterns revealed that individuals from the Shandong Peninsula share a close genetic affinity with ANEA, indicating long-term genetic continuity and mobility in the lower Yellow River basin since the early Neolithic period. Biological adaptive signatures, including those related to immune and metabolic pathways, were identified through analyses of haplotype homozygosity and allele frequency spectra. These signatures are linked to complex traits such as height and body mass index, which may be associated with adaptations to cold environments, dietary practices, and pathogen exposure. Additionally, allele frequency trajectories over time and a haplotype network of two highly differentiated genes, ABCC11 and SLC10A1, were delineated. These genes, which are associated with axillary odor and bilirubin metabolism, respectively, illustrate how local adaptations can influence the diversification of traits in East Asians. Conclusions: Our findings provide a comprehensive genomic dataset that elucidates the fine-scale genetic history and evolutionary trajectory of natural selection signals and disease susceptibility in Han Chinese populations. This study serves as a paradigm for integrating spatiotemporally diverse ancient genomes in the era of population genomic medicine. [ABSTRACT FROM AUTHOR]

Background: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding. Results: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively. Conclusion: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies. [ABSTRACT FROM AUTHOR]

Background: PTEN loss has been identified in various tumor types and is linked to unfavorable clinical outcomes. In addition to PTEN mutation, multiple mechanisms contribute to PTEN loss during tumor development. However, the natural selection process of PTEN-deficient tumor cells remains unclear. Here, we aimed at further elucidating the role of PTEN-L in tumor progression. Methods: PTEN knockout cell lines were generated using CRISPR/Cas9 technology. Ni-NTA affinity column chromatography was employed for PTEN-L purification. Tumor cell metastasis was evaluated in murine models and observed using the IVIS Spectrum Imaging System. RNA-sequencing, western blotting, PCR, flow cytometry, and cell proliferation assays were employed to investigate tumor cell dormancy and related mechanisms. Results: The chemotherapeutic drugs, cisplatin, paclitaxel, and doxorubicin, induced tumor cells to secrete PTEN-long (PTEN-L), which shields PTEN-deficient tumor cells from chemotherapy-induced apoptosis better than it shields PTEN-intact cells. Further investigation revealed that PTEN-L treatment induced dormancy in PTEN-null tumor cells, characterized by an increase in p16 and p27 levels, cell-cycle arrest, reduced cell proliferation, and enhanced DNA repair. Furthermore, PTEN-L treatment selectively promoted the accumulation and growth of PTEN-null tumor cells in the lungs of C57BL/6J mice, while evading immune surveillance. Mechanistically, PTEN-L induced dormancy in PTEN-null tumor cells by activating the p38 signaling pathway. Addition of a p38 inhibitor effectively reversed dormancy and growth of PTEN-deficient tumor cells in the lungs. We also demonstrated that PTEN expression played a pivotal role in determining the outcome of PTEN-L-mediated antitumor therapy. Conclusions: In summary, PTEN-L was identified as a potent inducer of dormancy in PTEN-deficient tumor cells, which increased their efficient selection within the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Background: In 2021 and 2023, the World Health Organization approved RTS,S/AS01 and R21/Matrix M malaria vaccines, respectively, for routine immunization of children in African countries with moderate to high transmission. These vaccines are made of Plasmodium falciparum circumsporozoite protein (PfCSP), but polymorphisms in the gene raise concerns regarding strain-specific responses and the long-term efficacy of these vaccines. This study assessed the Pfcsp genetic diversity, population structure and signatures of selection among parasites from areas of different malaria transmission intensities in Mainland Tanzania, to generate baseline data before the introduction of the malaria vaccines in the country. Methods: The analysis involved 589 whole genome sequences generated by and as part of the MalariaGEN Community Project. The samples were collected between 2013 and January 2015 from five regions of Mainland Tanzania: Morogoro and Tanga (Muheza) (moderate transmission areas), and Kagera (Muleba), Lindi (Nachingwea), and Kigoma (Ujiji) (high transmission areas). Wright's inbreeding coefficient (Fws), Wright's fixation index (FST), principal component analysis, nucleotide diversity, and Tajima's D were used to assess within-host parasite diversity, population structure and natural selection. Results: Based on Fws (< 0.95), there was high polyclonality (ranging from 69.23% in Nachingwea to 56.9% in Muheza). No population structure was detected in the Pfcsp gene in the five regions (mean FST = 0.0068). The average nucleotide diversity (π), nucleotide differentiation (K) and haplotype diversity (Hd) in the five regions were 4.19, 0.973 and 0.0035, respectively. The C-terminal region of Pfcsp showed high nucleotide diversity at Th2R and Th3R regions. Positive values for the Tajima's D were observed in the Th2R and Th3R regions consistent with balancing selection. The Pfcsp C-terminal sequences revealed 50 different haplotypes (H_1 to H_50), with only 2% of sequences matching the 3D7 strain haplotype (H_50). Conversely, with the NF54 strain, the Pfcsp C-terminal sequences revealed 49 different haplotypes (H_1 to H_49), with only 0.4% of the sequences matching the NF54 strain (Hap_49). Conclusions: The findings demonstrate high diversity of the Pfcsp gene with limited population differentiation. The Pfcsp gene showed positive Tajima's D values, consistent with balancing selection for variants within Th2R and Th3R regions. The study observed differences between the intended haplotypes incorporated into the design of RTS,S and R21 vaccines and those present in natural parasite populations. Therefore, additional research is warranted, incorporating other regions and more recent data to comprehensively assess trends in genetic diversity within this important gene. Such insights will inform the choice of alleles to be included in the future vaccines. [ABSTRACT FROM AUTHOR]

Background: Gene expression divergence between populations and between individuals can emerge from genetic variations within the genes and/or in the cis regulatory elements. Since epigenetic modifications regulate gene expression, it is conceivable that epigenetic variations in cis regulatory elements can also be a source of gene expression divergence. Results: In this study, we compared histone acetylation (namely, H3K9ac) profiles in two mouse strains of different subspecies origin, C57BL/6 J (B6) and MSM/Ms (MSM), as well as their F1 hybrids. This identified 319 regions of strain-specific acetylation, about half of which were observed between the alleles of F1 hybrids. While the allele-specific presence of the interferon regulatory factor 3 (IRF3) binding sequence was associated with allele-specific histone acetylation, we also revealed that B6-specific insertions of a short 3′ fragment of LINE-1 (L1) retrotransposon occur within or proximal to MSM-specific acetylated regions. Furthermore, even in hyperacetylated domains, flanking regions of non-polymorphic 3′ L1 fragments were hypoacetylated, suggesting a general activity of the 3′ L1 fragment to induce hypoacetylation. Indeed, we confirmed the binding of the 3′ region of L1 by three Krüppel-associated box domain-containing zinc finger proteins (KZFPs), which interact with histone deacetylases. These results suggest that even a short insertion of L1 would be excluded from gene- and acetylation-rich regions by natural selection. Finally, mRNA-seq analysis for F1 hybrids was carried out, which disclosed a link between allele-specific promoter/enhancer acetylation and gene expression. Conclusions: This study disclosed a number of genetic changes that have changed the histone acetylation levels during the evolution of mouse subspecies, a part of which is associated with gene expression changes. Insertions of even a very short L1 fragment can decrease the acetylation level in their neighboring regions and thereby have been counter-selected in gene-rich regions, which may explain a long-standing mystery of discrete genomic distribution of LINEs and SINEs. [ABSTRACT FROM AUTHOR]

Background: Saccharum spontaneumL. is a closely related species of sugarcane and has become an important genetic component of modern sugarcane cultivars. Stem development is one of the important factors for affecting the yield, while the molecular mechanism of stem development remains poorly understanding in S. spontaneum. Phenylalanine ammonia-lyase (PAL) is a vital component of both primary and secondary metabolism, contributing significantly to plant growth, development and stress defense. However, the current knowledge about PAL genes in S. spontaneum is still limited. Thus, identification and characterization of the PAL genes by transcriptome analysis will provide a theoretical basis for further investigation of the function of PAL gene in sugarcane. Results: In this study, 42 of PAL genes were identified, including 26 SsPAL genes from S. spontaneum, 8 ShPAL genes from sugarcane cultivar R570, and 8 SbPAL genes from sorghum. Phylogenetic analysis showed that SsPAL genes were divided into three groups, potentially influenced by long-term natural selection. Notably, 20 SsPAL genes were existed on chromosomes 4 and 5, indicating that they are highly conserved in S. spontaneum. This conservation is likely a result of the prevalence of whole-genome replications within this gene family. The upstream sequence of PAL genes were found to contain conserved cis-acting elements such as G-box and SP1, GT1-motif and CAT-box, which collectively regulate the growth and development of S. spontaneum. Furthermore, quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis showed that SsPAL genes of stem had a significantly upregulated than that of leaves, suggesting that they may promote the stem growth and development, particularly in the + 6 stem (The sixth cane stalk from the top to down) during the growth stage. Conclusions: The results of this study revealed the molecular characteristics of SsPAL genes and indicated that they may play a vital role in stem growth and development of S. spontaneum. Altogether, our findings will promote the understanding of the molecular mechanism of S. spontaneum stem development, and also contribute to the sugarcane genetic improving. [ABSTRACT FROM AUTHOR]

Background: Climate change is expected to alter the factors that drive changes in adaptive variation. This is especially true for species with long life spans and limited dispersal capabilities. Rapid climate changes may disrupt the migration of beneficial genetic variations, making it challenging for them to keep up with changing environments. Understanding adaptive genetic variations in tree species is crucial for conservation and effective forest management. Our study used landscape genomic analyses and phenotypic traits from a thorough sampling across the entire range of Quercus longinux, an oak species native to Taiwan, to investigate the signals of adaptation within this species. Results: Using ecological data, phenotypic traits, and 1,933 single-nucleotide polymorphisms (SNPs) from 205 individuals, we classified three genetic groups, which were also phenotypically and ecologically divergent. Thirty-five genes related to drought and freeze resistance displayed signatures of natural selection. The adaptive variation was driven by diverse environmental pressures such as low spring precipitation, low annual temperature, and soil grid sizes. Using linear-regression-based methods, we identified isolation by environment (IBE) as the optimal model for adaptive SNPs. Redundancy analysis (RDA) further revealed a substantial joint influence of demography, geology, and environments, suggesting a covariation between environmental gradients and colonization history. Lastly, we utilized adaptive signals to estimate the genetic offset for each individual under diverse climate change scenarios. The required genetic changes and migration distance are larger in severe climates. Our prediction also reveals potential threats to edge populations in northern and southeastern Taiwan due to escalating temperatures and precipitation reallocation. Conclusions: We demonstrate the intricate influence of ecological heterogeneity on genetic and phenotypic adaptation of an oak species. The adaptation is also driven by some rarely studied environmental factors, including wind speed and soil features. Furthermore, the genetic offset analysis predicted that the edge populations of Q. longinux in lower elevations might face higher risks of local extinctions under climate change. [ABSTRACT FROM AUTHOR]

Background: Whole-genome duplication and long terminal repeat retrotransposons (LTR-RTs) amplification in organisms are essential factors that affect speciation, local adaptation, and diversification of organisms. Understanding the karyotype projection and LTR-RTs amplification could contribute to untangling evolutionary history. This study compared the karyotype and LTR-RTs evolution in the genomes of eight oaks, a dominant lineage in Northern Hemisphere forests. Results: Karyotype projections showed that chromosomal evolution was relatively conservative in oaks, especially on chromosomes 1 and 7. Modern oak chromosomes formed through multiple fusions, fissions, and rearrangements after an ancestral triplication event. Species-specific chromosomal rearrangements revealed fragments preserved through natural selection and adaptive evolution. A total of 441,449 full-length LTR-RTs were identified from eight oak genomes, and the number of LTR-RTs for oaks from section Cyclobalanopsis was larger than in other sections. Recent amplification of the species-specific LTR-RTs lineages resulted in significant variation in the abundance and composition of LTR-RTs among oaks. The LTR-RTs insertion suppresses gene expression, and the suppressed intensity in gene regions was larger than in promoter regions. Some centromere and rearrangement regions indicated high-density peaks of LTR/Copia and LTR/Gypsy. Different centromeric regional repeat units (32, 78, 79 bp) were detected on different Q. glauca chromosomes. Conclusion: Chromosome fusions and arm exchanges contribute to the formation of oak karyotypes. The composition and abundance of LTR-RTs are affected by its recent amplification. LTR-RTs random retrotransposition suppresses gene expression and is enriched in centromere and chromosomal rearrangement regions. This study provides novel insights into the evolutionary history of oak karyotypes and the organization, amplification, and function of LTR-RTs. [ABSTRACT FROM AUTHOR]

Climate change is a threat to sustainable livestock production and livelihoods in the tropics. It has adverse impacts on feed and water availability, disease prevalence, production, environmental temperature, and biodiversity. Unravelling the drivers of local adaptation and understanding the underlying genetic variation in random mating indigenous livestock populations informs the design of genetic improvement programmes that aim to increase productivity and resilience. In the present study, we combined environmental, genomic, and phenotypic information of Ethiopian indigenous chickens to investigate their environmental adaptability. Through a hybrid sampling strategy, we captured wide biological and ecological variabilities across the country. Our environmental dataset comprised mean values of 34 climatic, vegetation and soil variables collected over a thirty-year period for 260 geolocations. Our biological dataset included whole genome sequences and quantitative measurements (on eight traits) from 513 individuals, representing 26 chicken populations spread along 4 elevational gradients (6–7 populations per gradient). We performed signatures of selection analyses ( and XP-EHH) to detect footprints of natural selection, and redundancy analyses (RDA) to determine genotype-environment and genotype-phenotype-associations. RDA identified 1909 outlier SNPs linked with six environmental predictors, which have the highest contributions as ecological drivers of adaptive phenotypic variation. The same method detected 2430 outlier SNPs that are associated with five traits. A large overlap has been observed between signatures of selection identified by and XP-EHH showing that both methods target similar selective sweep regions. Average genetic differences measured by are low between gradients, but XP-EHH signals are the strongest between agroecologies. Genes in the calcium signalling pathway, those associated with the hypoxia-inducible factor (HIF) transcription factors, and sports performance (GALNTL6) are under selection in high-altitude populations. Our study underscores the relevance of landscape genomics as a powerful interdisciplinary approach to dissect adaptive phenotypic and genetic variation in random mating indigenous livestock populations. [ABSTRACT FROM AUTHOR]

Background: Functional trade-offs through ecological specializations are hypothesized to become causes of adaptive phenotypic divergence under divergent natural selection, where intermediate phenotypes may have the lowest fitness. Evidence of phenotypic divergence in a trade-off between populations experiencing different environmental/ecological conditions is abundant. However, traits in divergent selection sometimes present non-discrete (unimodal) variability, including intermediate phenotypes, although the underlying mechanisms are poorly documented. A benthic cyprinid fish, Pseudogobio esocinus, in Lake Biwa, central Japan, exhibits a large non-discrete/continuous variation in mouthpart morphology (from wide to narrow) within a lake population. The variation is linked with individual diets (i.e., the compositions of two different types of prey) even at a single site, and thus the variability is hypothesized to persist under divergent selection for prey usage. As a first step toward understanding the persistence mechanisms, here I examined the presence of morphology-dependent feeding selectivity and a functional trade-off in a laboratory experiment. Results: When each experimental fish was simultaneously provided the different types of prey (chironomid larvae and amphipods), the fish mostly utilized chironomid larvae as primary prey. However, compared with the wider-mouthed fish, the narrower-mouthed fish took a larger proportion of amphipods as secondary prey by changing feeding (attacking) behavior. The intermediate-mouthed fish had lower feeding efficiency than the extreme-mouthed fish, indicating potential disadvantage of the intermediate phenotype. Conclusions: This experimental result supports the presence of morphology-dependent feeding performance and a functional trade-off with potential impacts on trait variability, which may favor specializations rather than generalizations. In the wild, however, there may be some situations for relaxing the trade-off, such as temporally fluctuating prey availability that could also favor generalizations depending on the conditions, and thus, both extreme and intermediate phenotypes may persist/coexist in a single habitat. Although further examinations, especially focusing on feeding efficiency for each prey type separated from the effects of prey selectivity, are needed, this case represents an opportunity to consider the possible mechanisms of the persistence of phenotypic variation that is maintained without divergence even in a trade-off. [ABSTRACT FROM AUTHOR]

Background: The underrepresentation of Hmong-Mien (HM) people in Asian genomic studies has hindered our comprehensive understanding of the full landscape of their evolutionary history and complex trait architecture. South China is a multi-ethnic region and indigenously settled by ethnolinguistically diverse HM, Austroasiatic (AA), Tai-Kadai (TK), Austronesian (AN), and Sino-Tibetan (ST) people, which is regarded as East Asia's initial cradle of biodiversity. However, previous fragmented genetic studies have only presented a fraction of the landscape of genetic diversity in this region, especially the lack of haplotype-based genomic resources. The deep characterization of demographic history and natural-selection-relevant genetic architecture of HM people was necessary. Results: We reported one HM-specific genomic resource and comprehensively explored the fine-scale genetic structure and adaptative features inferred from the genome-wide SNP data of 440 HM individuals from 33 ethnolinguistic populations, including previously unreported She. We identified solid genetic differentiation between HM people and Han Chinese at 7.64‒15.86 years ago (kya) and split events between southern Chinese inland (Miao/Yao) and coastal (She) HM people in the middle Bronze Age period and the latter obtained more gene flow from Ancient Northern East Asians. Multiple admixture models further confirmed that extensive gene flow from surrounding ST, TK, and AN people entangled in forming the gene pool of Chinese coastal HM people. Genetic findings of isolated shared unique ancestral components based on the sharing alleles and haplotypes deconstructed that HM people from the Yungui Plateau carried the breadth of previously unknown genomic diversity. We identified a direct and recent genetic connection between Chinese inland and Southeast Asian HM people as they shared the most extended identity-by-descent fragments, supporting the long-distance migration hypothesis. Uniparental phylogenetic topology and network-based phylogenetic relationship reconstruction found ancient uniparental founding lineages in southwestern HM people. Finally, the population-specific biological adaptation study identified the shared and differentiated natural selection signatures among inland and coastal HM people associated with physical features and immune functions. The allele frequency spectrum of cancer susceptibility alleles and pharmacogenomic genes showed significant differences between HM and northern Chinese people. Conclusions: Our extensive genetic evidence combined with the historical documents supported the view that ancient HM people originated from the Yungui regions associated with ancient "Three-Miao tribes" descended from the ancient Daxi-Qujialing-Shijiahe people. Then, some have recently migrated rapidly to Southeast Asia, and some have migrated eastward and mixed respectively with Southeast Asian indigenes, Liangzhu-related coastal ancient populations, and incoming southward ST people. Generally, complex population migration, admixture, and adaptation history contributed to the complicated patterns of population structure of geographically diverse HM people. [ABSTRACT FROM AUTHOR]

Background: Hemerocallis citrina Baroni is a traditional vegetable crop widely cultivated in eastern Asia for its high edible, medicinal, and ornamental value. The phenomenon of codon usage bias (CUB) is prevalent in various genomes and provides excellent clues for gaining insight into organism evolution and phylogeny. Comprehensive analysis of the CUB of mitochondrial (mt) genes can provide rich genetic information for improving the expression efficiency of exogenous genes and optimizing molecular-assisted breeding programmes in H. citrina. Results: Here, the CUB patterns in the mt genome of H. citrina were systematically analyzed, and the possible factors shaping CUB were further evaluated. Composition analysis of codons revealed that the overall GC (GCall) and GC at the third codon position (GC3) contents of mt genes were lower than 50%, presenting a preference for A/T-rich nucleotides and A/T-ending codons in H. citrina. The high values of the effective number of codons (ENC) are indicative of fairly weak CUB. Significant correlations of ENC with the GC3 and codon counts were observed, suggesting that not only compositional constraints but also gene length contributed greatly to CUB. Combined ENC-plot, neutrality plot, and Parity rule 2 (PR2)-plot analyses augmented the inference that the CUB patterns of the H. citrina mitogenome can be attributed to multiple factors. Natural selection, mutation pressure, and other factors might play a major role in shaping the CUB of mt genes, although natural selection is the decisive factor. Moreover, we identified a total of 29 high-frequency codons and 22 optimal codons, which exhibited a consistent preference for ending in A/T. Subsequent relative synonymous codon usage (RSCU)-based cluster and mt protein coding gene (PCG)-based phylogenetic analyses suggested that H. citrina is close to Asparagus officinalis, Chlorophytum comosum, Allium cepa, and Allium fistulosum in evolutionary terms, reflecting a certain correlation between CUB and evolutionary relationships. Conclusions: There is weak CUB in the H. citrina mitogenome that is subject to the combined effects of multiple factors, especially natural selection. H. citrina was found to be closely related to Asparagus officinalis, Chlorophytum comosum, Allium cepa, and Allium fistulosum in terms of their evolutionary relationships as well as the CUB patterns of their mitogenomes. Our findings provide a fundamental reference for further studies on genetic modification and phylogenetic evolution in H. citrina. [ABSTRACT FROM AUTHOR]

Background: The Aconitum genus is a crucial member of the Ranunculaceae family. There are 350 Aconitum species worldwide, with about 170 species found in China. These species are known for their various pharmacological effects and are commonly used to treat joint pain, cold abdominal pain, and other ailments. Codon usage bias (CUB) analysis contributes to evolutionary relationships and phylogeny. Based on protein-coding sequences (PCGs), we selected 48 species of Aconitum for CUB analysis. Results: The results revealed that Aconitum species had less than 50% GC content. Furthermore, the distribution of GC content was irregular and followed a trend of GC1 > GC2 > GC3, indicating a bias towards A/T bases. The relative synonymous codon usage (RSCU) heat map revealed the presence of conservative codons with slight variations within the genus. The effective number of codons (ENC)-Plot and the parity rule 2 (PR2)-bias plot analysis indicate that natural selection is the primary factor influencing the variation in codon usage. As a result, we screened various optimal codons and found that A/T bases were preferred as the last codon. Furthermore, our Maximum Likelihood (ML) analysis based on PCGs among 48 Aconitum species yielded results consistent with those obtained from complete chloroplast (cp.) genome data. This suggests that analyzing mutation in PCGs is an efficient method for demonstrating the phylogeny of species at the genus level. Conclusions: The CUB analysis of 48 species of Aconitum was mainly influenced by natural selection. This study reveals the CUB pattern of Aconitum and lays the foundation for future genetic modification and phylogenetic analyses. [ABSTRACT FROM AUTHOR]

Background: Apicomplexan protozoa are a diverse group of obligate intracellular parasites causing many diseases that affect humans and animals, such as malaria, toxoplasmosis, and cryptosporidiosis. Apicomplexan protozoa possess unique thioredoxins (Trxs) that have been shown to regulate various cellular processes including metabolic redox regulation, parasite survival, and host immune evasion. However, it is still unknown how synonymous codons are used by apicomplexan protozoa Trxs. Methods: Codon usage bias (CUB) is the unequal usage of synonymous codons during translation which leads to the over- or underrepresentation of certain nucleotide patterns. This imbalance in CUB can impact a variety of cellular processes including protein expression levels and genetic variation. This study analyzed the CUB of 32 Trx coding sequences (CDS) from 11 apicomplexan protozoa. Results: The results showed that both codon base composition and relative synonymous codon usage (RSCU) analysis revealed that AT-ended codons were more frequently used in Cryptosporidium spp. and Plasmodium spp., while the Eimeria spp., Babesia spp., Hammondia hammondi, Neospora caninum, and Toxoplasma gondii tended to end in G/C. The average effective number of codon (ENC) value of these apicomplexan protozoa is 46.59, which is > 35, indicating a weak codon preference among apicomplexan protozoa Trxs. Furthermore, the correlation analysis among codon base composition (GC1, GC2, GC3, GCs), codon adaptation index (CAI), codon bias index (CBI), frequency of optimal codons (FOP), ENC, general average hydropathicity (GRAVY), aromaticity (AROMO), length of synonymous codons (L_sym), and length of amino acids (L_aa) indicated the influence of base composition and codon usage indices on CUB. Additionally, the neutrality plot analysis, PR2-bias plot analysis, and ENC-GC3 plot analysis further demonstrated that natural selection plays an important role in apicomplexan protozoa Trxs codon bias. Conclusions: In conclusion, this study increased the understanding of codon usage characteristics and genetic evolution of apicomplexan protozoa Trxs, which expanded new ideas for vaccine and drug research. [ABSTRACT FROM AUTHOR]

Background: Conventional wisdom in evolutionary theory considers aging as a non-selected byproduct of natural selection. Based on this, conviction aging was regarded as an inevitable phenomenon. It was also thought that in the wild organisms tend to die from diseases, predation and other accidents before they could reach the time when senescence takes its course. Evidence has accumulated, however, that aging is not inevitable and there are organisms that show negative aging even. Furthermore, old age does play a role in the deaths of many different organisms in the wild also. The hypothesis of programmed aging posits that a limited lifespan can evolve as an adaptation (i.e., positively selected for) in its own right, partly because it can enhance evolvability by eliminating "outdated" genotypes. A major shortcoming of this idea is that non-aging sexual individuals that fail to pay the demographic cost of aging would be able to steal good genes by recombination from aging ones. Results: Here, we show by a spatially explicit, individual-based simulation model that aging can positively be selected for if a sufficient degree of kin selection complements directional selection. Under such conditions, senescence enhances evolvability because the rate of aging and the rate of recombination play complementary roles. The selected aging rate is highest at zero recombination (clonal reproduction). In our model, increasing extrinsic mortality favors evolved aging by making up free space, thereby decreasing competition and increasing drift, even when selection is stabilizing and the level of aging is set by mutation-selection balance. Importantly, higher extrinsic mortality is not a substitute for evolved aging under directional selection either. Reduction of relatedness decreases the evolved level of aging; chance relatedness favors non-aging genotypes. The applicability of our results depends on empirical values of directional and kin selection in the wild. Conclusions: We found that aging can positively be selected for in a spatially explicit population model when sufficiently strong directional and kin selection prevail, even if reproduction is sexual. The view that there is a conceptual link between giving up clonal reproduction and evolving an aging genotype is supported by computational results. [ABSTRACT FROM AUTHOR]

Rhodophyta are among the closest known relatives of green plants. Studying the codons of their genomes can help us understand the codon usage pattern and characteristics of the ancestor of green plants. By studying the codon usage pattern of all available red algae, it was found that although there are some differences among species, high-bias genes in most red algae prefer codons ending with GC. Correlation analysis, Nc-GC3s plots, parity rule 2 plots, neutrality plot analysis, differential protein region analysis and comparison of the nucleotide content of introns and flanking sequences showed that the bias phenomenon is likely to be influenced by local mutation pressure and natural selection, the latter of which is the dominant factor in terms of translation accuracy and efficiency. It is worth noting that selection on translation accuracy could even be detected in the low-bias genes of individual species. In addition, we identified 15 common optimal codons in seven red algae except for G. sulphuraria for the first time, most of which were found to be complementary and bound to the tRNA genes with the highest copy number. Interestingly, tRNA modification was found for the highly degenerate amino acids of all multicellular red algae and individual unicellular red algae, which indicates that highly biased genes tend to use modified tRNA in translation. Our research not only lays a foundation for exploring the characteristics of codon usage of the red algae as green plant ancestors, but will also facilitate the design and performance of transgenic work in some economic red algae in the future. [ABSTRACT FROM AUTHOR]

Background: The chloroplast genome of plants is known for its small size and low mutation and recombination rates, making it a valuable tool in plant phylogeny, molecular evolution, and population genetics studies. Codon usage bias, an important evolutionary feature, provides insights into species evolution, gene function, and the expression of exogenous genes. Coffee, a key crop in the global tropical agricultural economy, trade, and daily life, warrants investigation into its codon usage bias to guide future research, including the selection of efficient heterologous expression systems for coffee genetic transformation. Results: Analysis of the codon utilization patterns in the chloroplast genomes of three Coffea species revealed a high degree of similarity among them. All three species exhibited similar base compositions, with high A/T content and low G/C content and a preference for A/T-ending codons. Among the 30 high-frequency codons identified, 96.67% had A/T endings. Fourteen codons were identified as ideal. Multiple mechanisms, including natural selection, were found to influence the codon usage patterns in the three coffee species, as indicated by ENc-GC3s mapping, PR2 analysis, and neutral analysis. Nicotiana tabacum and Saccharomyces cerevisiae have potential value as the heterologous expression host for three species of coffee genes. Conclusion: This study highlights the remarkable similarity in codon usage patterns among the three coffee genomes, primarily driven by natural selection. Understanding the gene expression characteristics of coffee and elucidating the laws governing its genetic evolution are facilitated by investigating the codon preferences in these species. The findings can enhance the efficacy of exogenous gene expression and serve as a basis for future studies on coffee evolution. [ABSTRACT FROM AUTHOR]

Background: Knowledge of the diversity of invasion ligands in malaria parasites in endemic regions is essential to understand how natural selection influences genetic diversity of these ligands and their feasibility as possible targets for future vaccine development. In this study the diversity of four genes for merozoite invasion ligands was studied in Ecuadorian isolates of Plasmodium vivax. Methods: Eighty-eight samples from P. vivax infected individuals from the Coast and Amazon region of Ecuador were obtained between 2012 and 2015. The merozoite invasion genes pvmsp-1-19, pvdbpII, pvrbp1a-2 and pvama1 were amplified, sequenced, and compared to the Sal-1 strain. Polymorphisms were mapped and genetic relationships between haplotypes were determined. Results: Only one nonsynonymous polymorphism was detected in pvmsp-1-19, while 44 nonsynonymous polymorphisms were detected in pvdbpII, 56 in pvrbp1a-2 and 33 in pvama1. While haplotypes appeared to be more related within each area of study and there was less relationship between parasites of the coastal and Amazon regions of the country, diversification processes were observed in the two Amazon regions. The highest haplotypic diversity for most genes occurred in the East Amazon of the country. The high diversity observed in Ecuadorian samples is closer to Brazilian and Venezuelan isolates, but lower than reported in other endemic regions. In addition, departure from neutrality was observed in Ecuadorian pvama1. Polymorphisms for pvdbpII and pvama1 were associated to B-cell epitopes. Conclusions: pvdbpII and pvama1 genetic diversity found in Ecuadorian P. vivax was very similar to that encountered in other malaria endemic countries with varying transmission levels and segregated by geographic region. The highest diversity of P. vivax invasion genes in Ecuador was found in the Amazonian region. Although selection appeared to have small effect on pvdbpII and pvrbp1a-2, pvama1 was influenced by significant balancing selection. [ABSTRACT FROM AUTHOR]

Background: Sheep genomes undergo numerous genes losses, gains and mutation that generates genome variability among breeds of the same species after long time natural and artificial selection. However, the microevolution of native sheep in northwest China remains elusive. Our aim was to compare the genomes and relevant reproductive traits of four sheep breeds from different climatic environments, to unveil the selection challenges that this species cope with, and the microevolutionary differences in sheep genomes. Here, we resequenced the genomes of 4 representative sheep breeds in northwest China, including Kazakh sheep and Duolang sheep of native breeds, and Hu sheep and Suffolk sheep of exotic breeds with different reproductive characteristics. Results: We found that these four breeds had a similar expansion experience from ~ 10,000 to 1,000,000 years ago. In the past 10,000 years, the selection intensity of the four breeds was inconsistent, resulting in differences in reproductive traits. We explored the sheep variome and selection signatures by FST and θπ. The genomic regions containing genes associated with different reproductive traits that may be potential targets for breeding and selection were detected. Furthermore, non-synonymous mutations in a set of plausible candidate genes and significant differences in their allele frequency distributions across breeds with different reproductive characteristics were found. We identified PAK1, CYP19A1 and PER1 as a likely causal gene for seasonal reproduction in native sheep through qPCR, Western blot and ELISA analyses. Also, the haplotype frequencies of 3 tested gene regions related to reproduction were significantly different among four sheep breeds. Conclusions: Our results provide insights into the microevolution of native sheep and valuable genomic information for identifying genes associated with important reproductive traits in sheep. [ABSTRACT FROM AUTHOR]

Background: Accessory proteins have diverse roles in coronavirus pathobiology. One of them in SARS-CoV (the causative agent of the severe acute respiratory syndrome outbreak in 2002–2003) is encoded by the open reading frame 8 (ORF8). Among the most dramatic genomic changes observed in SARS-CoV isolated from patients during the peak of the pandemic in 2003 was the acquisition of a characteristic 29-nucleotide deletion in ORF8. This deletion cause splitting of ORF8 into two smaller ORFs, namely ORF8a and ORF8b. Functional consequences of this event are not entirely clear. Results: Here, we performed evolutionary analyses of ORF8a and ORF8b genes and documented that in both cases the frequency of synonymous mutations was greater than that of nonsynonymous ones. These results suggest that ORF8a and ORF8b are under purifying selection, thus proteins translated from these ORFs are likely to be functionally important. Comparisons with several other SARS-CoV genes revealed that another accessory gene, ORF7a, has a similar ratio of nonsynonymous to synonymous mutations suggesting that ORF8a, ORF8b, and ORF7a are under similar selection pressure. Conclusions: Our results for SARS-CoV echo the known excess of deletions in the ORF7a-ORF7b-ORF8 complex of accessory genes in SARS-CoV-2. A high frequency of deletions in this gene complex might reflect recurrent searches in "functional space" of various accessory protein combinations that may eventually produce more advantageous configurations of accessory proteins similar to the fixed deletion in the SARS-CoV ORF8 gene. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies (GWASs) have identified many single-nucleotide polymorphisms (SNPs) associated with complex phenotypes in the European (EUR) population; however, the extent to which EUR-associated SNPs can be generalized to other populations such as East Asian (EAS) is not clear. Results: By leveraging summary statistics of 31 phenotypes in the EUR and EAS populations, we first evaluated the difference in heritability between the two populations and calculated the trans-ethnic genetic correlation. We observed the heritability estimates of some phenotypes varied substantially across populations and 53.3% of trans-ethnic genetic correlations were significantly smaller than one. Next, we examined whether EUR-associated SNPs of these phenotypes could be identified in EAS using the trans-ethnic false discovery rate method while accounting for winner's curse for SNP effect in EUR and difference of sample sizes in EAS. We found on average 54.5% of EUR-associated SNPs were also significant in EAS. Furthermore, we discovered non-significant SNPs had higher effect heterogeneity, and significant SNPs showed more consistent linkage disequilibrium and allele frequency patterns between the two populations. We also demonstrated non-significant SNPs were more likely to undergo natural selection. Conclusions: Our study revealed the extent to which EUR-associated SNPs could be significant in the EAS population and offered deep insights into the similarity and diversity of genetic architectures underlying phenotypes in distinct ancestral groups. [ABSTRACT FROM AUTHOR]

Background: Genome-wide association studies have detected a large number of single-nucleotide polymorphisms (SNPs) associated with complex traits in diverse ancestral groups. However, the trans-ethnic similarity and diversity of genetic architecture is not well understood currently. Results: By leveraging summary statistics of 37 traits from East Asian (Nmax=254,373) or European (Nmax=693,529) populations, we first evaluated the trans-ethnic genetic correlation (ρg) and found substantial evidence of shared genetic overlap underlying these traits between the two populations, with ranging from 0.53 (se = 0.11) for adult-onset asthma to 0.98 (se = 0.17) for hemoglobin A1c. However, 88.9% of the genetic correlation estimates were significantly less than one, indicating potential heterogeneity in genetic effect across populations. We next identified common associated SNPs using the conjunction conditional false discovery rate method and observed 21.7% of trait-associated SNPs can be identified simultaneously in both populations. Among these shared associated SNPs, 20.8% showed heterogeneous influence on traits between the two ancestral populations. Moreover, we demonstrated that population-common associated SNPs often exhibited more consistent linkage disequilibrium and allele frequency pattern across ancestral groups compared to population-specific or null ones. We also revealed population-specific associated SNPs were much likely to undergo natural selection compared to population-common associated SNPs. Conclusions: Our study provides an in-depth understanding of similarity and diversity regarding genetic architecture for complex traits across diverse populations, and can assist in trans-ethnic association analysis, genetic risk prediction, and causal variant fine mapping. [ABSTRACT FROM AUTHOR]

Background: Snake venoms are trophic adaptations that represent an ideal model to examine the evolutionary factors that shape polymorphic traits under strong natural selection. Venom compositional variation is substantial within and among venomous snake species. However, the forces shaping this phenotypic complexity, as well as the potential integrated roles of biotic and abiotic factors, have received little attention. Here, we investigate geographic variation in venom composition in a wide-ranging rattlesnake (Crotalus viridis viridis) and contextualize this variation by investigating dietary, phylogenetic, and environmental variables that covary with venom. Results: Using shotgun proteomics, venom biochemical profiling, and lethality assays, we identify 2 distinct divergent phenotypes that characterize major axes of venom variation in this species: a myotoxin-rich phenotype and a snake venom metalloprotease (SVMP)-rich phenotype. We find that dietary availability and temperature-related abiotic factors are correlated with geographic trends in venom composition. Conclusions: Our findings highlight the potential for snake venoms to vary extensively within species, for this variation to be driven by biotic and abiotic factors, and for the importance of integrating biotic and abiotic variation for understanding complex trait evolution. Links between venom variation and variation in biotic and abiotic factors indicate that venom variation likely results from substantial geographic variation in selection regimes that determine the efficacy of venom phenotypes across populations and snake species. Our results highlight the cascading influence of abiotic factors on biotic factors that ultimately shape venom phenotype, providing evidence for a central role of local selection as a key driver of venom variation. [ABSTRACT FROM AUTHOR]

Background: Theory suggests that the genetic architecture of traits under divergent natural selection influences how easily reproductive barriers evolve and are maintained between species. Divergently selected traits with a simple genetic architecture (few loci with major phenotypic effects) should facilitate the establishment and maintenance of reproductive isolation between species that are still connected by some gene flow. While empirical support for this idea appears to be mixed, most studies test the influence of trait architectures on reproductive isolation only indirectly. Petunia plant species are, in part, reproductively isolated by their different pollinators. To investigate the genetic causes and consequences of this ecological isolation, we deciphered the genetic architecture of three floral pollination syndrome traits in naturally occurring hybrids between the widespread Petunia axillaris and the highly endemic and endangered P. exserta. Results: Using population genetics, Bayesian linear mixed modelling and genome-wide association studies, we found that the three pollination syndrome traits vary in genetic architecture. Few genome regions explain a majority of the variation in flavonol content (defining UV floral colour) and strongly predict the trait value in hybrids irrespective of interspecific admixture in the rest of their genomes. In contrast, variation in pistil exsertion and anthocyanin content (defining visible floral colour) is controlled by many genome-wide loci. Opposite to flavonol content, the genome-wide proportion of admixture between the two species predicts trait values in their hybrids. Finally, the genome regions strongly associated with the traits do not show extreme divergence between individuals representing the two species, suggesting that divergent selection on these genome regions is relatively weak within their contact zones. Conclusions: Among the traits analysed, those with a more complex genetic architecture are best maintained in association with the species upon their secondary contact. We propose that this maintained genotype–phenotype association is a coincidental consequence of the complex genetic architectures of these traits: some of their many underlying small-effect loci are likely to be coincidentally linked with the actual barrier loci keeping these species partially isolated upon secondary contact. Hence, the genetic architecture of a trait seems to matter for the outcome of hybridization not only then when the trait itself is under selection. [ABSTRACT FROM AUTHOR]

Background: Gene duplication is a prevalent phenomenon and a major driving force underlying genome evolution. The process leading to the fixation of gene duplicates following duplication is critical to understand how genome evolves but remains fragmentally understood. Most previous studies on gene retention are based on gene duplicate analyses in single reference genome. No population-based comparative gene retention analysis has been performed to date. Results: Taking advantage of recently published genomic data in Triticeae, we dissected a divergent homogentisate phytyltransferase (HPT2) lineage caught in the middle stage of gene fixation following duplication. The presence/absence of HPT2 in barley (diploid), wild emmer (tetraploid), and bread wheat (hexaploid) pangenome lines appears to be associated with gene dosage constraint and environmental adaption. Based on these observations, we adopted a phylogeny-based orthology inference approach and performed comparative gene retention analyses across barley, wild emmer, and bread wheat. This led to the identification of 326 HPT2-pattern-like genes at whole genome scale, representing a pool of gene duplicates in the middle stage of gene fixation. Majority of these HPT2-pattern-like genes were identified as small-scale duplicates, such as dispersed, tandem, and proximal duplications. Natural selection analyses showed that HPT2-pattern-like genes have experienced relaxed selection pressure, which is generally accompanied with partial positive selection and transcriptional divergence. Functional enrichment analyses showed that HPT2-pattern-like genes are over-represented with molecular-binding and defense response functions, supporting the potential role of environmental adaption during gene retention. We also observed that gene duplicates from larger gene family are more likely to be lost, implying a gene dosage constraint effect. Further comparative gene retention analysis in barley and bread wheat pangenome lines revealed combined effects of species-specific selection and gene dosage constraint. Conclusions: Comparative gene retention analyses at the population level support gene dosage constraint, environmental adaption, and species-specific selection as three factors that may affect gene retention following gene duplication. Our findings shed light on the evolutionary process leading to the retention of newly formed gene duplicates and will greatly improve our understanding on genome evolution via duplication. [ABSTRACT FROM AUTHOR]

Background: Rhizoctonia solani is a polyphagous fungal pathogen that causes diseases in crops. The fungal strains are classified into anastomosis groups (AGs); however, genomic complexity, diversification into the AGs and the evolution of pathogenicity-associated genes remain poorly understood. Results: We report a recent whole-genome duplication and sequential segmental duplications in AG1-IA strains of R. solani. Transposable element (TE) clusters have caused loss of synteny in the duplicated blocks and introduced differential structural alterations in the functional domains of several pathogenicity-associated paralogous gene pairs. We demonstrate that the TE-mediated structural variations in a glycosyl hydrolase domain and a GMC oxidoreductase domain in two paralogous pairs affect the pathogenicity of R. solani. Furthermore, to investigate the association of TEs with the natural selection and evolution of pathogenicity, we sequenced the genomes of forty-two rice field isolates of R. solani AG1-IA. The genomic regions with high population mutation rates and with the lowest nucleotide diversity are enriched with TEs. Genetic diversity analysis predicted the genes that are most likely under diversifying and purifying selections. We present evidence that a smaller variant of a glucosamine phosphate N-acetyltransferase (GNAT) protein, predicted to be under purifying selection, and an LPMP_AA9 domain-containing protein, predicted to be under diversifying selection, are important for the successful pathogenesis of R. solani in rice as well as tomato. Conclusions: Our study has unravelled whole-genome duplication, TE-mediated neofunctionalization of genes and evolution of pathogenicity traits in R. solani AG1-IA. The pathogenicity-associated genes identified during the study can serve as novel targets for disease control. [ABSTRACT FROM AUTHOR]

The subgenus Rhizirideum in the genus Allium consists of 38 species worldwide and forms five sections (A. sect. Rhizomatosa, A. sect. Tenuissima, A. sect. Rhizirideum, A. sect. Eduardia, and A. sect. Caespitosoprason), A. sect. Caespitosoprason being merged into A. sect. Rhizomatosa recently. Previous studies on this subgenus mainly focused on separate sections. To investigate the inter-section and inter-subgenera phylogenetic relationships and adaptive evolution of A. subg. Rhizirideum, we selected thirteen representative species, which cover five sections of this subgenus and can represent four typical phenotypes of it. We conducted the comparative plastome analysis with our thirteen plastomes. And phylogenetic inferences with CDSs and complete sequences of plastomes of our thirteen species and another fifty-four related species were also performed. As a result, the A. subg. Rhizirideum plastomes were relatively conservative in structure, IR/SC borders, codon usage, and repeat sequence. In phylogenetic results, the inter-subgenera relationships among A. subg. Rhizirideum and other genus Allium subgenera were generally similar to the previous reports. In contrast, the inter-section relationships within our subgenus A. subg. Rhizirideum were newly resolved in this study. A. sect. Rhizomatosa and A. sect. Tenuissima were sister branches, which were then clustered with A. sect. Rhizirideum and A. sect. Eduardia successively. However, Allium Polyrhizum Turcz. ex Regel, type species of A. sect. Caespitosoprason, was resolved as the basal taxon of A. subg. Rhizirideum. Allium siphonanthum J. M. Xu was also found in clade A. subg. Cyathophora instead of clade A. subg. Rhizirideum. The selective pressure analysis was also conducted, and most protein-coding genes were under purifying selection. At the same time, just one gene, ycf2, was found under positive selection, and another three genes (rbcL, ycf1a, ycf1b) presented relaxed selection, which were all involved in the photosynthesis. The low temperature, dry climate, and high altitude of the extreme habitats where A. subg. Rhizirideum species grow might impose intense natural selection forces on their plastome genes for photosynthesis. In summary, our research provides new insights into the phylogeny and adaptive evolution of A. subg. Rhizirideum. Moreover, we suggest that the positions of the A. subg. Rhizirideum species A. polyrhizum and A. siphonanthum should be reconsidered. [ABSTRACT FROM AUTHOR]

Background: Thousands of years of natural and artificial selection since the domestication of the horse has shaped the distinctive genomes of Chinese Mongolian horse populations. Consequently, genomic signatures of selection can provide insights into the human-mediated selection history of specific traits and evolutionary adaptation to diverse environments. Here, we used genome-wide SNPs from five distinct Chinese Mongolian horse populations to identify genomic regions under selection for the population-specific traits, gait, black coat colour, and hoof quality. Other global breeds were used to identify regional-specific signatures of selection. Results: We first identified the most significant selection peak for the Wushen horse in the region on ECA23 harbouring DMRT3, the major gene for gait. We detected selection signatures encompassing several genes in the Baicha Iron Hoof horse that represent good biological candidates for hoof health, including the CSPG4, PEAK1, EXPH5, WWP2 and HAS3 genes. In addition, an analysis of regional subgroups (Asian compared to European) identified a single locus on ECA3 containing the ZFPM1 gene that is a marker of selection for the major domestication event leading to the DOM2 horse clade. Conclusions: Genomic variation at these loci in the Baicha Iron Hoof may be leveraged in other horse populations to identify animals with superior hoof health or those at risk of hoof-related pathologies. The overlap between the selection signature in Asian horses with the DOM2 selection peak raises questions about the nature of horse domestication events, which may have involved a prehistoric clade other than DOM2 that has not yet been identified. [ABSTRACT FROM AUTHOR]

Background: The Phenomenon of codon usage bias exists in the genomes of prokaryotes and eukaryotes. The codon usage pattern is affected by environmental factors, base mutation, gene flow and gene expression level, among which natural selection and mutation pressure are the main factors. The study of codon preference is an effective method to analyze the source of evolutionary driving forces in organisms. Epimedium species are perennial herbs with ornamental and medicinal value distributed worldwide. The chloroplast genome is self-replicating and maternally inherited which is usually used to study species evolution, gene expression and genetic transformation. Results: The results suggested that chloroplast genomes of Epimedium species preferred to use codons ending with A/U. 17 common high-frequency codons and 2–6 optimal codons were found in the chloroplast genomes of Epimedium species, respectively. According to the ENc-plot, PR2-plot and neutrality-plot, the formation of codon preference in Epimedium was affected by multiple factors, and natural selection was the dominant factor. By comparing the codon usage frequency with 4 common model organisms, it was found that Arabidopsis thaliana, Populus trichocarpa, and Saccharomyces cerevisiae were suitable exogenous expression receptors. Conclusion: The evolutionary driving force in the chloroplast genomes of 10 Epimedium species probably comes from mutation pressure. Our results provide an important theoretical basis for evolutionary analysis and transgenic research of chloroplast genes. [ABSTRACT FROM AUTHOR]

Background: Transmission-blocking vaccines (TBVs) target the sexual stages of malaria parasites to reduce or interrupt the transmission cycle in human and mosquito populations. The genetic diversity of TBVs candidate antigens, Pvs25 and Pvs28, in Plasmodium vivax could provide evidence for the development of TBVs. Methods: Dry blood spots from P. vivax patients were collected from Dandong, Suining, Hainan, Nyingchi, Tengchong, and Yingjiang in China. The pvs25 and pvs28 genes were amplified and sequenced. The genetic diversity of pvs25 and pvs28 were analyzed using DNASTAR, MEGA6, and DnaSP 5.0 programs. Results: A total of 377 samples were collected, among which 324 and 272 samples were successfully amplified in the pvs25 and pvs28 genes, respectively. Eight haplotypes were identified in Pvs25, for which the predominant mutation was I130T with 100% prevalence. A variety of 22 haplotypes in Pvs28 were identified. The number of GSGGE/D repeats of Pvs28 was a range of 4–8, among which, high (7–8) and low (4–5) copy numbers of tandem repeats were found in haplotypes H2 and H17, respectively. The nucleotide diversity of pvs28 (π = 0.00305 ± 0.00061) was slightly higher than that of pvs25 (π = 0.00146 ± 0.00007), thus they were not significantly different (P > 0.05). The Tajima's D value of pvs25 was positive whereas pvs28 was negative, which indicated that both genes were affected by natural selection. Conclusion: The genetic diversity of pvs25 and pvs28 genes in China was relatively limited, which provided valuable information for TBVs design and optimization. [ABSTRACT FROM AUTHOR]

Background: Selection schemes distort inference when estimating differences between treatments or genetic associations between traits, and may degrade prediction of outcomes, e.g., the expected performance of the progeny of an individual with a certain genotype. If input and output measurements are not collected on random samples, inferences and predictions must be biased to some degree. Our paper revisits inference in quantitative genetics when using samples stemming from some selection process. The approach used integrates the classical notion of fitness with that of missing data. Treatment is fully Bayesian, with inference and prediction dealt with, in an unified manner. While focus is on animal and plant breeding, concepts apply to natural selection as well. Examples based on real data and stylized models illustrate how selection can be accounted for in four different situations, and sometimes without success. Results: Our flexible "soft selection" setting helps to diagnose the extent to which selection can be ignored. The clear connection between probability of missingness and the concept of fitness in stylized selection scenarios is highlighted. It is not realistic to assume that a fixed selection threshold t holds in conceptual replication, as the chance of selection depends on observed and unobserved data, and on unequal amounts of information over individuals, aspects that a "soft" selection representation addresses explicitly. There does not seem to be a general prescription to accommodate potential distortions due to selection. In structures that combine cross-sectional, longitudinal and multi-trait data such as in animal breeding, balance is the exception rather than the rule. The Bayesian approach provides an integrated answer to inference, prediction and model choice under selection that goes beyond the likelihood-based approach, where breeding values are inferred indirectly. Conclusions: The approach used here for inference and prediction under selection may or may not yield the best possible answers. One may believe that selection has been accounted for diligently, but the central problem of whether statistical inferences are good or bad does not have an unambiguous solution. On the other hand, the quality of predictions can be gauged empirically via appropriate training-testing of competing methods. [ABSTRACT FROM AUTHOR]

Background: Understanding the micro--evolutionary response of populations to demographic declines is a major goal in evolutionary and conservation biology. In small populations, genetic drift can lead to an accumulation of deleterious mutations, which will increase the risk of extinction. However, demographic recovery can still occur after extreme declines, suggesting that natural selection may purge deleterious mutations, even in extremely small populations. The Chatham Island black robin (Petroica traversi) is arguably the most inbred bird species in the world. It avoided imminent extinction in the early 1980s and after a remarkable recovery from a single pair, a second population was established and the two extant populations have evolved in complete isolation since then. Here, we analysed 52 modern and historical genomes to examine the genomic consequences of this extreme bottleneck and the subsequent translocation. Results: We found evidence for two-fold decline in heterozygosity and three- to four-fold increase in inbreeding in modern genomes. Moreover, there was partial support for temporal reduction in total load for detrimental variation. In contrast, compared to historical genomes, modern genomes showed a significantly higher realised load, reflecting the temporal increase in inbreeding. Furthermore, the translocation induced only small changes in the frequency of deleterious alleles, with the majority of detrimental variation being shared between the two populations. Conclusion: Our results highlight the dynamics of mutational load in a species that recovered from the brink of extinction, and show rather limited temporal changes in mutational load. We hypothesise that ancestral purging may have been facilitated by population fragmentation and isolation on several islands for thousands of generations and may have already reduced much of the highly deleterious load well before human arrival and introduction of pests to the archipelago. The majority of fixed deleterious variation was shared between the modern populations, but translocation of individuals with low mutational load could possibly mitigate further fixation of high-frequency deleterious variation. [ABSTRACT FROM AUTHOR]

Background: Introgression from extinct Neanderthal and Denisovan human species has been shown to contribute to the genetic pool of modern human populations and their phenotypic spectrum. Evidence of how Neanderthal introgression shaped the genetics of human traits and diseases has been extensively studied in populations of European descent, with signatures of admixture reported for instance in genes associated with pigmentation, immunity, and metabolic traits. However, limited information is currently available about the impact of archaic introgression on other ancestry groups. Additionally, to date, no study has been conducted with respect to the impact of Denisovan introgression on the health and disease of modern populations. Here, we compare the way evolutionary pressures shaped the genetics of complex traits in East Asian and European populations, and provide evidence of the impact of Denisovan introgression on the health of East Asian and Central/South Asian populations. Results: Leveraging genome-wide association statistics from the Biobank Japan and UK Biobank, we assessed whether Denisovan and Neanderthal introgression together with other evolutionary genomic signatures were enriched for the heritability of physiological and pathological conditions in populations of East Asian and European descent. In EAS, Denisovan-introgressed loci were enriched for coronary artery disease heritability (1.69-fold enrichment, p=0.003). No enrichment for archaic introgression was observed in EUR. We also performed a phenome-wide association study of Denisovan and Neanderthal alleles in six ancestry groups available in the UK Biobank. In EAS, the Denisovan-introgressed SNP rs62391664 in the major histocompatibility complex region was associated with albumin/globulin ratio (beta=−0.17, p=3.57×10−7). Neanderthal-introgressed alleles were associated with psychiatric and cognitive traits in EAS (e.g., "No Bipolar or Depression"-rs79043717 beta=−1.5, p=1.1×10−7), and with blood biomarkers (e.g., alkaline phosphatase-rs11244089 beta=0.1, p=3.69×10−116) and red hair color (rs60733936 beta=−0.86, p=4.49×10−165) in EUR. In the other ancestry groups, Neanderthal alleles were associated with several traits, also including the use of certain medications (e.g., Central/South East Asia: indapamide – rs732632 beta=−2.38, p=5.22×10−7). Conclusions: Our study provides novel evidence regarding the impact of archaic introgression on the genetics of complex traits in worldwide populations, highlighting the specific contribution of Denisovan introgression in EAS populations. [ABSTRACT FROM AUTHOR]

Background: Cancer evolution consists of a stepwise acquisition of genetic and epigenetic changes, which alter the gene expression profiles of cells in a particular tissue and result in phenotypic alterations acted upon by natural selection. The recurrent appearance of specific genetic lesions across individual cancers and cancer types suggests the existence of certain "driver mutations," which likely make up the major contribution to tumors' selective advantages over surrounding normal tissue and as such are responsible for the most consequential aspects of the cancer cells' gene expression patterns and phenotypes. We hypothesize that such mutations are likely to cluster with specific dichotomous shifts in the expression of the genes they most closely control, and propose GMMchi, a Python package that leverages Gaussian Mixture Modeling to detect and characterize bimodal gene expression patterns across cancer samples, as a tool to analyze such correlations using 2 × 2 contingency table statistics. Results: Using well-defined simulated data, we were able to confirm the robust performance of GMMchi, reaching 85% accuracy with a sample size of n = 90. We were also able to demonstrate a few examples of the application of GMMchi with respect to its capacity to characterize background florescent signals in microarray data, filter out uninformative background probe sets, as well as uncover novel genetic interrelationships and tumor characteristics. Our approach to analysing gene expression analysis in cancers provides an additional lens to supplement traditional continuous-valued statistical analysis by maximizing the information that can be gathered from bulk gene expression data. Conclusions: We confirm that GMMchi robustly and reliably extracts bimodal patterns from both colorectal cancer (CRC) cell line-derived microarray and tumor-derived RNA-Seq data and verify previously reported gene expression correlates of some well-characterized CRC phenotypes. Availability: The Python package GMMchi and our cell line microarray data used in this paper is available for downloading on GitHub at https://github.com/jeffliu6068/GMMchi. [ABSTRACT FROM AUTHOR]

Background: Many animals live in intimate associations with a species-rich microbiome. A key factor in maintaining these beneficial associations is fidelity, defined as the stability of associations between hosts and their microbiota over multiple host generations. Fidelity has been well studied in terrestrial hosts, particularly insects, over longer macroevolutionary time. In contrast, little is known about fidelity in marine animals with species-rich microbiomes at short microevolutionary time scales, that is at the level of a single host population. Given that natural selection acts most directly on local populations, studies of microevolutionary partner fidelity are important for revealing the ecological and evolutionary processes that drive intimate beneficial associations within animal species. Results: In this study on the obligate symbiosis between the gutless marine annelid Olavius algarvensis and its consortium of seven co-occurring bacterial symbionts, we show that partner fidelity varies across symbiont species from strict to absent over short microevolutionary time. Using a low-coverage sequencing approach that has not yet been applied to microbial community analyses, we analysed the metagenomes of 80 O. algarvensis individuals from the Mediterranean and compared host mitochondrial and symbiont phylogenies based on single-nucleotide polymorphisms across genomes. Fidelity was highest for the two chemoautotrophic, sulphur-oxidizing symbionts that dominated the microbial consortium of all O. algarvensis individuals. In contrast, fidelity was only intermediate to absent in the sulphate-reducing and spirochaetal symbionts with lower abundance. These differences in fidelity are likely driven by both selective and stochastic forces acting on the consistency with which symbionts are vertically transmitted. Conclusions: We hypothesize that variable degrees of fidelity are advantageous for O. algarvensis by allowing the faithful transmission of their nutritionally most important symbionts and flexibility in the acquisition of other symbionts that promote ecological plasticity in the acquisition of environmental resources. 9fKqRNiGMfEagdmyCMhS4T Video Abstract [ABSTRACT FROM AUTHOR]