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Polyploid rice and its reverted diploid show rich phenotypic variation and strong heterosis, showing great breeding value. However, the genomic differences among tetraploids, counterpart common diploids, tetraploid-revertant diploids, and hybrid descendants are unclear. In this work, we bred a new excellent two-line hybrid rice variety, Y Liang You Duo Hui 14 (HTRM12), using Haitian tetraploid self-reverted diploid (HTRM2). Furthermore, we comparatively analyzed the important agronomic traits and genome-wide variations of those closest relatives, Haitian diploid (HT2), Haitian tetraploid (HT4), HTRM2, and HTRM12 in detail, based on multiple phenotypic investigations, genome resequencing, and bioinformatics analysis. The results of agronomic traits analysis and genome-wide variation analysis of single nucleotide polymorphism (SNP), insertion–deletion (InDel), and copy number variation (CNV) show that HT4 and HTRM2 had abundant phenotypic and genomic variations compared to HT2. HTRM2 can inherit important traits and variations from HT4. This implies that tetraploid self-reverted diploid has high potential in creating excellent breeding materials and in breeding breakthrough hybrid rice varieties. Our study verifies the feasibility that polyploid rice could be used as a mutation carrier for creating variations and provides genomic information, new breeding materials, and a new way of application for tetraploid rice breeding. [ABSTRACT FROM AUTHOR]

ABSTRACT Fungi were some of the earliest organismal systems used to explore mutational processes and its phenotypic consequences on members of a species. Yeasts that cause significant human disease were quickly incorporated into these investigations to define the genetic and phenotypic drivers of virulence. Among Candida species, Candida albicans has emerged as a model for studying genomic processes of evolution because of its clinical relevance, relatively small genome, and ability to tolerate complex chromosomal changes. Here, we describe major recent findings that used evolution of strains from defined genetic backgrounds to delineate mutational and adaptative processes and include how nascent exploration into naturally occurring variation is contributing to these conceptual frameworks. Ultimately, efforts to discern adaptive mechanisms used by C. albicans will continue to divulge new biology and can better inform treatment regimens for the increasing prevalence of fungal disease.

A pangenome captures the genomic diversity for a species, derived from a collection of genetic sequences of diverse populations. Advances in sequencing technologies have given rise to three primary methods for pangenome construction and analysis: de novo assembly and comparison, reference genome-based iterative assembly, and graph-based pangenome construction. Each method presents advantages and challenges in processing varying amounts and structures of DNA sequencing data. With the emergence of high-quality genome assemblies and advanced bioinformatic tools, the graph-based pangenome is emerging as an advanced reference for exploring the biological and functional implications of genetic variations. [ABSTRACT FROM AUTHOR]

A pangenome encompasses the complete genetic diversity of a species, by assembling a range of representative individuals from various populations. This review describes the advances in plant pangenomics, tracing its evolution since the initial plant genome sequencing in 2000, and provides comprehensive best-practice advice to build a linear or graphical pangenome, delineating the strengths and limitations of different pangenome construction methods. The review also examines the challenges in pangenome data visualisation, the challenges of graph-based pangenomes and their utility in investigating the potential function of genome variation. Furthermore, we examine the application of pangenomes in plant breeding, including the identification of genetic diversity for crop improvement, and the integration of multi-omics data into pangenome databases to advance plant breeding.

Among the Hevea species, rubber tree (Hevea brasiliensis) is the most important source of natural rubber. In previous studies, we sequenced the complete nuclear and chloroplast genomes of Hevea species, providing an invaluable resource for studying their phylogeny, disease resistance, and breeding. However, given that plant mitochondrial genomes are more complex and more difficult to assemble than that of the other organelles, little is known about their mitochondrial genome, which limits the comprehensive understanding of Hevea genomic evolution. In this study, we sequenced and assembled the mitochondrial genomes of four Hevea species. The four mitochondrial genomes had consistent GC contents, codon usages and AT skews. However, there were significant differences in the genome lengths and sequence repeats. Specifically, the circular mitochondrial genomes of the four Hevea species ranged from 935,732 to 1,402,206 bp, with 34–35 unique protein-coding genes, 35–38 tRNA genes, and 6–13 rRNA genes. In addition, there were 17,294–46,552 bp intergenomic transfer fragments between the chloroplast and mitochondrial genomes, consisting of eight intact genes (psaA, rrn16S, tRNA-Val, rrn5S, rrn4.5S, tRNA-Arg, tRNA-Asp, and tRNA-Asn), intergenic spacer regions and partial gene sequences. The evolutionary position of Hevea species, crucial for understanding its adaptive strategies and relation to other species, was verified by phylogenetic analysis based on the protein-coding genes in the mitochondrial genomes of 21 Malpighiales species. The findings from this study not only provide valuable insights into the structure and evolution of the Hevea mitochondrial genome but also lay the foundation for further molecular, evolutionary studies, and genomic breeding studies on rubber tree and other Hevea species, thereby potentially informing conservation and utilization strategies.

HIV infection continues to be a major global public health issue. The population heterogeneity in susceptibility or resistance to HIV-1 and progression upon infection is attributable to, among other factors, host genetic variation. Therefore, identifying population-specific variation and genetic modifiers of HIV infectivity can catapult the invention of effective strategies against HIV-1 in African populations. Here, we investigated whole genome sequences of 390 unrelated HIV-positive and -negative individuals from Botswana. We report 27.7 million single nucleotide variations (SNVs) in the complete genomes of Botswana nationals, of which 2.8 million were missing in public databases. Our population structure analysis revealed a largely homogenous structure in the Botswana population. Admixture analysis showed elevated components shared between the Botswana population and the Niger-Congo (65.9%), Khoe-San (32.9%), and Europeans (1.1%) ancestries in the population of Botswana. Statistical significance of the mutational burden of deleterious and loss-of-function variants per gene against a null model was estimated. The most deleterious variants were enriched in five genes: ACTRT2 (the Actin Related Protein T2), HOXD12 (homeobox D12), ABCB5 (ATP binding cassette subfamily B member 5), ATP8B4 (ATPase phospholipid transporting 8B4) and ABCC12 (ATP Binding Cassette Subfamily C Member 12). These genes are enriched in the glycolysis and gluconeogenesis (p < 2.84e-6) pathways and therefore, may contribute to the emerging field of immunometabolism in which therapy against HIV-1 infection is being evaluated. Published transcriptomic evidence supports the role of the glycolysis/gluconeogenesis pathways in the regulation of susceptibility to HIV, and that cumulative effects of genetic modifiers in glycolysis/gluconeogenesis pathways may potentially have effects on the expression and clinical variability of HIV-1. Identified genes and pathways provide novel avenues for other interventions, with the potential for informing the design of new therapeutics.

Advances in DNA sequencing technology have sparked a genomics revolution, driving breakthroughs in plant genetics and crop breeding. Recently, the focus has shifted from cataloging genetic diversity in plants to exploring their functional significance and delivering beneficial alleles for crop improvement. This transformation has been facilitated by the increasing adoption of whole-genome resequencing. In this review, we summarize the current progress of population-based genome resequencing studies and how these studies affect crop breeding. A total of 187 land plants from 163 countries have been resequenced, comprising 54 413 accessions. As part of resequencing efforts 367 traits have been surveyed and 86 genome-wide association studies have been conducted. Economically important crops, particularly cereals, vegetables, and legumes, have dominated the resequencing efforts, leaving a gap in 49 orders, including Lycopodiales, Liliales, Acorales, Austrobaileyales, and Commelinales. The resequenced germplasm is distributed across diverse geographic locations, providing a global perspective on plant genomics. We highlight genes that have been selected during domestication, or associated with agronomic traits, and form a repository of candidate genes for future research and application. Despite the opportunities for cross-species comparative genomics, many population genomic datasets are not accessible, impeding secondary analyses. We call for a more open and collaborative approach to population genomics that promotes data sharing and encourages contribution-based credit policy. The number of plant genome resequencing studies will continue to rise with the decreasing DNA sequencing costs, coupled with advances in analysis and computational technologies. This expansion, in terms of both scale and quality, holds promise for deeper insights into plant trait genetics and breeding design. To date, 187 land plants, including 54 413 accessions from various habitats, have been resequenced to investigate their origins, domestication, and radiation and to identify loci conferring desirable traits to accelerate breeding programs, which has enhanced the understanding of plant population genetics and expanded the reservoir of genes valuable for agronomic practices and plant studies. This review summarizes the current progress of population-based genome resequencing studies and how these studies affect crop breeding. [ABSTRACT FROM AUTHOR]

Roses are important plants, and they are cultivated worldwide for their beautiful flowers, remarkable scent, and nutritious hips. In this study, we re-sequenced the whole genomes of 57 rose cultivars and one wild species that originated from different regions around the world and had different scents, aiming to evaluate their genetic structure and to detect the potential signature of the selective sweep between different scent groups with single-nucleotide polymorphism (SNP) and indel markers. The roses were sequenced at an average depth of 6× to the reference genome of Rosa 'Old blush'. A total of 2,375,949 SNPs were obtained. The SNP numbers varied among the 58 samples, with an average of 1,271,906 per sample. The phylogeny and population structure revealed that the roses could be divided into three main clusters; however, the groups were not consistent in terms of geographic origin or scent classification. These indicated that rose cultivars have a complex genetic background due to the extensive hybridization between cultivated roses or wild rosa species worldwide. A selective sweep analysis was conducted to detect the selection signatures in rose scent traits. A total of 2430 candidate genes were identified in the strong scent groups, and were at the top 5% FST compared to the moderate group. These genes were significantly enriched in the KEGG pathways of tyrosine metabolism, cyanoamino acid metabolism, alpha-linolenic acid metabolism (13 genes), and phenylpropanoid biosynthesis (30 genes). When the low-scent group was used as the control, 2604 candidate genes were identified at the top 5% FST that were significantly enriched in the KEGG pathways of alpha-linolenic acid metabolism (15 genes), and glutathione metabolism (23 genes). We also observed genes enriched in pathways including the linoleic acid metabolism (five genes), diterpenoid biosynthesis (six genes), and monoterpenoid biosynthesis (seven genes), although they were not significant. These implied a positive selection of rose cultivars with a strong fragrance in terms of fatty acid derivatives, terpenoids and benzenoids/phenylpropanoids during rose breeding. Our study establishes a foundation for the further large-scale characterization of rose germplasm, improving the genetic knowledge of the background of roses. [ABSTRACT FROM AUTHOR]

Eukaryotic cells contain multiple types of duplicated sequences. Typical examples are tandem repeat sequences including telomeres, centromeres, rDNA genes and transposable elements. Most of these sequences are unstable; thus, their copy numbers or sequences change rapidly in the course of evolution. In this review, I will describe roles of subtelomere regions, which are located adjacent to telomeres at chromosome ends, and recent discoveries about their sequence variation. [ABSTRACT FROM AUTHOR]

The emergence of drug resistance significantly hampers the treatment of human infections, including those caused by fungal pathogens such as Candida species. Candida glabrata ranks as the second most common cause of candidiasis worldwide, supported by rapid acquisition of resistance to azole and echinocandin antifungals frequently prompted by single nucleotide polymorphisms (SNPs) in resistance associated genes, such as PDR1 (azole resistance) or FKS1/2 (echinocandin resistance). To determine the frequency of polymorphisms and genome rearrangements as the possible genetic basis of C. glabrata drug resistance, we assessed genomic variation across 94 globally distributed isolates with distinct resistance phenotypes, whose sequence is deposited in GenBank. The genomes of three additional clinical isolates were sequenced, in this study, including two azole resistant strains that did not display Gain-Of-Function (GOF) mutations in the transcription factor encoding gene PDR1. Genomic variations in susceptible isolates were used to screen out variants arising from genome diversity and to identify variants exclusive to resistant isolates. More than half of the azole or echinocandin resistant isolates do not possess exclusive polymorphisms in PDR1 or FKS1/2, respectively, providing evidence of alternative genetic basis of antifungal resistance. We also identified copy number variations consistently affecting a subset of chromosomes. Overall, our analysis of the genomic and phenotypic variation across isolates allowed to pinpoint, in a genome-wide scale, genetic changes enriched specifically in antifungal resistant strains, which provides a first step to identify additional determinants of antifungal resistance. Specifically, regarding the newly sequenced strains, a set of mutations/genes are proposed to underlie the observed unconventional azole resistance phenotype.

The mitochondrion is a maternally inherited organelle that produces approximately 90% of cellular energy. The mitochondrial genome (mtDNA) consists of 13 genes that are critical components of oxidative phosphorylation. Identifying and understanding variation within this genome could elucidate differences in metabolic and physiological traits, specifically growth efficiency in cattle. Our aim is to identify how variation in the mitochondrial genome influences efficiency in beef cattle. Low-pass sequencing data (average 0.5X coverage of the autosomes) were collected (Neogen) from 49 animals within the UNL herd (composite Simmental, Red Angus, and Gelbvieh). The data were trimmed and mapped (BWA-MEM) to the ARS-UCD1.2 cattle genome. After variant impacts were predicted (Ensembl VEP) haplotype networks were created to visualize variation among samples. Over 60X coverage was achieved across the mitochondrial genome, on average. Excluding the D-loop, 62 variants were identified in the 49 animals: 2 tRNA, 6 rRNA, and 54 coding single nucleotide polymorphisms (SNPs). These 62 variants were encompassed in 23 unique haplotypes. Of the coding variants, 13 were nonsynonymous and found in the following genes encoding components of oxidative phosphorylation: ND1 (n = 3), ND2 (n = 1), ND3 (n = 1), ND4 (n = 1), ND5 (n = 1), ND6 (n = 3), COX3 (n = 2), and CYTB (n = 1). Nine unique haplotypes were present considering only nonsynonymous variants. Nonsynonymous mutations were identified in complex I genes (ND1-6), in the complex IV gene COX3, and in CYTB, which is involved in multiple processes including the electron transport chain. These data, from a closed herd at UNL, support that there is a great deal of mtDNA variation present among beef cattle for which to analyze the impact of mitochondrial genotype on animal efficiency. Performance data demonstrate variation in average daily gain (ADG) and residual feed intake (RFI) in this herd, with a mean ADG of 1.95 kg/d (SD = 0.23 kg/d) and a mean RFI of -0.11 kg (SD = 0.57 kg). Data on individual feed intake, growth rates, and carcass performance values will continue to be collected on all animals sequenced. Based upon these data we hypothesize that variation in the mitochondrial genome will be associated with altered complex I and IV activity. For a more comprehensive understanding of this variation, the sample size will be expanded to over 1,500 animals in the next 2 yr. Overall, from our initial analysis of the mitochondrial genomes from 49 animals, we have identified 62 variants that we anticipate will explain variation in cellular and growth efficiency. [ABSTRACT FROM AUTHOR]

BackgroundThe genomes of halophilic archaea (haloarchaea) often comprise multiple replicons. Genomic variation in haloarchaea has been linked to viral infection pressure and, in the case of Antarctic communities, can be caused by intergenera gene exchange. To expand understanding of genome variation and biogeography of Antarctic haloarchaea, here we assessed genomic variation between two strains of Halorubrum lacusprofundi that were isolated from Antarctic hypersaline lakes from different regions (Vestfold Hills and Rauer Islands). To assess variation in haloarchaeal populations, including the presence of genomic islands, metagenomes from six hypersaline Antarctic lakes were characterised.ResultsThe sequence of the largest replicon of each Hrr. lacusprofundi strain (primary replicon) was highly conserved, while each of the strains' two smaller replicons (secondary replicons) were highly variable. Intergenera gene exchange was identified, including the sharing of a type I-B CRISPR system. Evaluation of infectivity of an Antarctic halovirus provided experimental evidence for the differential susceptibility of the strains, bolstering inferences that strain variation is important for modulating interactions with viruses. A relationship was found between genomic structuring and the location of variation within replicons and genomic islands, demonstrating that the way in which haloarchaea accommodate genomic variability relates to replicon structuring. Metagenome read and contig mapping and clustering and scaling analyses demonstrated biogeographical patterning of variation consistent with environment and distance effects. The metagenome data also demonstrated that specific haloarchaeal species dominated the hypersaline systems indicating they are endemic to Antarctica.ConclusionThe study describes how genomic variation manifests in Antarctic-lake haloarchaeal communities and provides the basis for future assessments of Antarctic regional and global biogeography of haloarchaea.

Background: The family Columbidae is known as the pigeon family and contains approximately 351 species and 50 genera. Compared to the wealth of biological and genomic information on these Columba livia var. domesteca, information on Columba rupestris and Streptopelia orientalis has been rather limited. The C. rupestris population size is decreasing in Korea. Objectives: Whole-genome sequencing and identification of population characterization of each species based genome variation on 9 Korean pigeon and dove samples, namely, six hill pigeon (C. rupestris), one rock pigeon (C. livia var. domestica) and two oriental turtle dove (S. orientalis) samples. Results: The whole genome of 9 genotypes were sequenced and mapped to the C. livia reference genome. Sequence alignment showed over 96% identity in C. rupestris and 94% identity in S. orientalis to the reference genome (GenBank assembly accession: GCA_001887795.1). Sequence variations, including single nucleotide polymorphisms (SNPs), insertions and deletions (InDels), and structural variations, revealed that intergenus (Columba vs. Streptopelia) variations were approximately four times higher than intragenus variations (C. livia vs. C. rupestris). Of the two Columba species, C. livia var. domestica is closer to S. orientalis than C. rupestris. Pairwise sequentially Markovian coalescent (PSMC) demographic history analysis revealed that the three species underwent a common population bottleneck between 105 and 120 Kya; since then, the effective population sizes of the rock pigeon and oriental turtle dove have increased. Conclusion: The effective population size of the hill pigeon, an Endangered Species of Grade II in Korea, has increased slowly from the second severe bottleneck that occurred approximately 0.5–1.4 × 104 years ago. Our results showed no relationship between copy number variation in the Norrie disease protein (NDP) regulatory regions and plumage color patterns. We report the first comparative analysis of three pigeon genomes. [ABSTRACT FROM AUTHOR]

Dwarf ornamental bamboos are a class of low shrub plants with minor interspecific morphological differences and are difficult to distinguish by traditional classification. In order to identify this type of bamboo species at the molecular level, we sequenced the genomes of the chloroplasts in seven species of dwarf ornamental bamboo: Pleioblastus argenteostriatus (Regel) Nakai, Pleioblastus fortunei (Van Houtte) Nakai, Pleioblastus pygmaeus (Miq.) Nakai, Pleioblastus pygmaeus 'Disticha', Sasaella glabra (Nakai) Koidz., Sasaella glabra 'Albostriata' and Sasaella kongosanensis 'Aureostriatus' using high-throughput sequencing. The quadripartite structure of the chloroplast genomes is typical, with sizes ranging from 139,031 bp (P. argenteostriatus) to 139,759 bp (S. kongosanensis 'Aureostriatus'). The genomes contain 116 genes, including four rRNA genes, 30 tRNA genes and 82 protein-coding genes. Four hotspots, including ndhI-ndhA, trnC-rpoB, petB and ccsA, and a total of 46 simple sequence repeats (SSRs) were identified as potential variable markers for species delimitation and population structure analysis. The phylogenetic analyses of chloroplast genomes of seven dwarf ornamental bamboos indicates that these bamboo species can be classified into three categories: Sasaella I, Pleioblastus II and Pleioblastus III. Except S. kongosanensis 'Aureostriatus', the other six species were distributed into two branches, indicating that both S.glabra and S. glabra 'Albostriata' belong to Pleioblastus Nakai genus. There are four mutations on the chloroplast genomes of S. glabra and S. glabra 'Albostriata', suggesting that the mutations may contribute to their obvious different leaf morphologies. Our study reveals the chloroplast structural variations and their phylogenetic relationship and mutation dynamics in seven dwarf ornamental bamboos and also facilitates studies on population genetics, taxonomy and interspecific identification in dwarf bamboo plants. [ABSTRACT FROM AUTHOR]

Tumor heterogeneity significantly increases the difficulty of tumor treatment. The same drugs and treatment methods have different effects on different tumor subtypes. Therefore, tumor heterogeneity is one of the main sources of poor prognosis, recurrence and metastasis. At present, there have been some computational methods to study tumor heterogeneity from the level of genome, transcriptome, and histology, but these methods still have certain limitations. In this study, we proposed an epistasis and heterogeneity analysis method based on genomic single nucleotide polymorphism (SNP) data. First of all, a maximum correlation and maximum consistence criteria was designed based on Bayesian network score K2 and information entropy for evaluating genomic epistasis. As the number of SNPs increases, the epistasis combination space increases sharply, resulting in a combination explosion phenomenon. Therefore, we next use an improved genetic algorithm to search the SNP epistatic combination space for identifying potential feasible epistasis solutions. Multiple epistasis solutions represent different pathogenic gene combinations, which may lead to different tumor subtypes, that is, heterogeneity. Finally, the XGBoost classifier is trained with feature SNPs selected that constitute multiple sets of epistatic solutions to verify that considering tumor heterogeneity is beneficial to improve the accuracy of tumor subtype prediction. In order to demonstrate the effectiveness of our method, the power of multiple epistatic recognition and the accuracy of tumor subtype classification measures are evaluated. Extensive simulation results show that our method has better power and prediction accuracy than previous methods.

Stroke is a neurological syndrome, and it leads to 5.8 million mortalities worldwide annually. In the Kingdom of Saudi Arabia (KSA), stroke was predicted to have 57%-67% incidence rate against a population growth rate of 12.8%. Current state of the art in stroke research in KSA is limited to epidemiological, prevalence data and there is a lack of genetic basis of stroke among Saudi individuals and their risk for disease traits. Despite the better health care services in KSA, a genetic approach is needed for stroke, as it is a manifestation of both monogenic Mendelian and polygenic disorder. Here, we propose to analyze and annotate Saudi specific genome variations associated with stroke. In this study, we explored the non-coding and genic regions using 28 whole genomes of individuals from Saudi population. We explored stroke susceptible genes for additional variation. Analysis of 49 genes which are stroke-associated for single nucleotide polymorphism (SNPs), obtained from whole genomes, reveals variations in atleast 13 candidate genes. In conclusion, whole genome sequencing and annotation of SNPs in the population of Saudi Arabia provide an insight into genetics of stroke. This analysis furnish a list of probable novel Saudi specific mutations that could be associated with stroke, once a cohort of disease data can beobtained. In addition, we conjecture that, by identifying these mutational signatures, stroke subtype and susceptibility to stroke can be uncovered in the future.

Roses are important plants, and they are cultivated worldwide for their beautiful flowers, remarkable scent, and nutritious hips. In this study, we re-sequenced the whole genomes of 57 rose cultivars and one wild species that originated from different regions around the world and had different scents, aiming to evaluate their genetic structure and to detect the potential signature of the selective sweep between different scent groups with single-nucleotide polymorphism (SNP) and indel markers. The roses were sequenced at an average depth of 6× to the reference genome of Rosa ‘Old blush’. A total of 2,375,949 SNPs were obtained. The SNP numbers varied among the 58 samples, with an average of 1,271,906 per sample. The phylogeny and population structure revealed that the roses could be divided into three main clusters; however, the groups were not consistent in terms of geographic origin or scent classification. These indicated that rose cultivars have a complex genetic background due to the extensive hybridization between cultivated roses or wild rosa species worldwide. A selective sweep analysis was conducted to detect the selection signatures in rose scent traits. A total of 2430 candidate genes were identified in the strong scent groups, and were at the top 5% FST compared to the moderate group. These genes were significantly enriched in the KEGG pathways of tyrosine metabolism, cyanoamino acid metabolism, alpha-linolenic acid metabolism (13 genes), and phenylpropanoid biosynthesis (30 genes). When the low-scent group was used as the control, 2604 candidate genes were identified at the top 5% FST that were significantly enriched in the KEGG pathways of alpha-linolenic acid metabolism (15 genes), and glutathione metabolism (23 genes). We also observed genes enriched in pathways including the linoleic acid metabolism (five genes), diterpenoid biosynthesis (six genes), and monoterpenoid biosynthesis (seven genes), although they were not significant. These implied a positive selection of rose cultivars with a strong fragrance in terms of fatty acid derivatives, terpenoids and benzenoids/phenylpropanoids during rose breeding. Our study establishes a foundation for the further large-scale characterization of rose germplasm, improving the genetic knowledge of the background of roses.

Bacteria often change their genetic and physiological traits to survive in harsh environments. To determine whether, in various strains of Burkholderia glumae, genomic diversity is associated with the ability to adapt to everchanging environments, whole genomes of 44 isolates from different hosts and regions were analyzed. Whole-genome phylogenetic analysis of the 44 isolates revealed six clusters and two divisions. While all isolates possessed chromosomes 1 and 2, strains BGR80S and BGR81S had one chromosome resulting from the merging of the two chromosomes. Upon comparison of genomic structures to the prototype BGR1, inversions, deletions, and rearrangements were found within or between chromosomes 1 and/or 2 in the other isolates. When three isolates--BGR80S, BGR15S, and BGR21S, representing clusters III, IV, and VI, respectively--were grown in Luria-Bertani medium, spontaneous null mutations were identified in qsmR encoding a quorum-sensing master regulator. Six days after subculture, qsmR mutants were found at detectable frequencies in BGR15S and BGR21S, and reached approximately 40% at 8 days after subculture. However, the qsmR mutants appeared 2 days after subculture in BGR80S and dominated the population, reaching almost 80%. No qsmR mutant was detected at detectable frequency in BGR1 or BGR13S. The spontaneous qsmR mutants outcompeted their parental strains in the co-culture. Daily addition of glucose or casamino acids to the batch cultures of BGR80S delayed emergence of qsmR mutants and significantly reduced their incidence. These results indicate that spontaneous qsmR mutations are correlated with genomic structures and nutritional conditions. [ABSTRACT FROM AUTHOR]

Genome annotation is the process of identifying functional components in a genome sequence, which can directly assign biological significance to the sequence, thus facilitating the exploration and analsis of genome functions. Genome annotation can help researchers understand the genome from three levels. The first is the annotation at the nucleotide level, which mainly determines the physical locations of genes, RNA, repetitive sequences. and other components in the DNA sequence, including specific location information such as transcription initiation, translation initiation, and exon boundaries. At the same time, the difference in the variation frequency of the variation in different populations can be obtained via annotation, which is the basis for the interpretation of the phenotypic differences of different populations. The second is the annotation at the protein level, which mainly interprets the possible functional abnormalities of genes or mutations, and evaluates the impact of the location of the mutations in the genes and the types of mutations on protein changes. The third type is biological function/process annotation, which mainly interprets the impact of different gene interactions on biological processes and pathways, and can explain the impact of genes or regulatory elements on life biochemical processes or functions from the perspective of systems biology. Since the completion of the Human Genome Project, countries across the world have successively launched genome sequencing projects, completed detailed gene polymorphism maps of human genes, and recorded annotation information such as variation distribution and frequency differences of different phenotypic groups. Based on the existing knowledge of annotation databases, a highly accurate and efficient genome annotation system for large-scale populations was developed, realizing fully automated functional annotation analysis and calculation of large-scale population variation data, and further assisting future research on variation distribution of population genetics and other aspects. [ABSTRACT FROM AUTHOR]

Objective: The SARS-CoV-2 pathogen has established endemicity in humans. This necessitates the development of rapid genetic surveillance methodologies to serve as an adjunct to existing comprehensive, albeit though slower, genome sequencing-driven approaches. Methods: A total of 21,789 complete genomes were downloaded from GISAID on May 28, 2020, for analyses. We have defined the major clades and subclades of circulating SARS-CoV-2 genomes. A rapid sequencing-based genotyping protocol was developed and tested on SARS-CoV-2-positive RNA samples by next-generation sequencing. Results: We describe eleven major mutation events that defined five major clades (G614, S84, V251, I378, and D392) of globally-circulating viral populations. The clades can be specifically identified using an 11-nucleotide genetic barcode. An analysis of amino acid variation in SARS-CoV-2 proteins provided evidence of substitution events in the viral proteins involved in both host entry and genome replication. Conclusion: Globally-circulating SARS-CoV-2 genomes could be classified into five major clades based on mutational profiles defined by an 11-nucleotide barcode. We have successfully developed a multiplexed sequencing-based, rapid genotyping protocol for high-throughput classification of major clade types of SARS-CoV-2 in clinical samples. This barcoding strategy will be required to monitor genetic diversity decrease as treatment and vaccine approaches become widely available.

Objective The Wannan Black pig is a typical Chinese indigenous, disease-resistant pig breed with high fertility, and a crude-feed tolerance that has been bred by artificial selection in the south of Anhui province for a long time. However, genome variation, genetic relationships with other pig breeds, and domestication, remain poorly understood. Here, we focus on elucidating the genetic characteristics of the Wannan Black pig and identifying selection signatures during domestication and breeding. Methods We identified the whole-genome variation in the Wannan Black pig and performed population admixture analyses to determine genetic relationships with other domesticated pig breeds and wild boars. Then, we identified the selection signatures between the Wannan Black pig and Asian wild boars in 100-kb windows sliding in 10 kb steps by using two approaches: the fixation index (FST) and π ratios. Results Resequencing the Wannan Black pig genome yielded 501.52 G of raw data. After calling single-nucleotide variants (SNVs) and insertions/deletions (InDels), we identified 21,316,754 SNVs and 5,067,206 InDels (2,898,582 inserts and 2,168,624 deletions). Additionally, we found genes associated with growth, immunity, and digestive functions. Conclusion Our findings help in explaining the unique genetic and phenotypic characteristics of Wannan Black pigs, which in turn can be informative for future breeding programs of Wannan Black pigs.

Abstract Background Lotus (Nelumbo nucifera) is an aquatic plant with important agronomic, horticulture, art and religion values. It was the basal eudicot species occupying a critical phylogenetic position in flowering plants. After the domestication for thousands of years, lotus has differentiated into three cultivated types -flower lotus, seed lotus and rhizome lotus. Although the phenotypic and genetic differentiations based on molecular markers have been reported, the variation on whole-genome level among the different lotus types is still ambiguous. Results In order to reveal the evolution and domestication characteristics of lotus, a total of 69 lotus accessions were selected, including 45 cultivated accessions, 22 wild sacred lotus accessions, and 2 wild American lotus accessions. With Illumina technology, the genomes of these lotus accessions were resequenced to > 13× raw data coverage. On the basis of these genomic data, 25 million single-nucleotide polymorphisms (SNPs) were identified in lotus. Population analysis showed that the rhizome and seed lotus were monophyletic and genetically homogeneous, whereas the flower lotus was biphyletic and genetically heterogeneous. Using population SNP data, we identified 1214 selected regions in seed lotus, 95 in rhizome lotus, and 37 in flower lotus. Some of the genes in these regions contributed to the essential domestication traits of lotus. The selected genes of seed lotus mainly affected lotus seed weight, size and nutritional quality. While the selected genes were responsible for insect resistance, antibacterial immunity and freezing and heat stress resistance in flower lotus, and improved the size of rhizome in rhizome lotus, respectively. Conclusions The genome differentiation and a set of domestication genes were identified from three types of cultivated lotus- flower lotus, seed lotus and rhizome lotus, respectively. Among cultivated lotus, flower lotus showed the greatest variation. The domestication genes may show agronomic importance via enhancing insect resistance, improving seed weight and size, or regulating lotus rhizome size. The domestication history of lotus enhances our knowledge of perennial aquatic crop evolution, and the obtained dataset provides a basis for future genomics-enabled breeding.

Fungi were some of the earliest organismal systems used to explore mutational processes and its phenotypic consequences on members of a species. Yeasts that cause significant human disease were quickly incorporated into these investigations to define the genetic and phenotypic drivers of virulence. Among Candida species, Candida albicans has emerged as a model for studying genomic processes of evolution because of its clinical relevance, relatively small genome, and ability to tolerate complex chromosomal changes. Here, we describe major recent findings that used evolution of strains from defined genetic backgrounds to delineate mutational and adaptative processes and include how nascent exploration into naturally occurring variation is contributing to these conceptual frameworks. Ultimately, efforts to discern adaptive mechanisms used by C. albicans will continue to divulge new biology and can better inform treatment regimens for the increasing prevalence of fungal disease., Competing Interests: The authors declare no conflict of interest.

To investigate the pattern of chloroplast genome variation in Triticeae, we comprehensively analyzed the indels in protein-coding genes and intergenic sequence, gene loss/pseudonization, intron variation, expansion/contraction in inverted repeat regions, and the relationship between sequence characteristics and chloroplast genome size in 34 monogenomic Triticeae plants. Ancestral genome reconstruction suggests that major length variations occurred in four-stem branches of monogenomic Triticeae followed by independent changes in each genus. It was shown that the chloroplast genome sizes of monogenomic Triticeae were highly variable. The chloroplast genome of Pseudoroegneria , Dasypyrum , Lophopyrum , Thinopyrum , Eremopyrum , Agropyron , Australopyrum , and Henradia in Triticeae had evolved toward size reduction largely because of pseudogenes elimination events and length deletion fragments in intergenic. The Aegilops / Triticum complex, Taeniatherum , Secale , Crithopsis , Herteranthelium , and Hordeum in Triticeae had a larger chloroplast genome size. The large size variation in major lineages and their subclades are most likely consequences of adaptive processes since these variations were significantly correlated with divergence time and historical climatic changes. We also found that several intergenic regions, such as pet N– trn C and psb E– pet L containing unique genetic information, which can be used as important tools to identify the maternal relationship among Triticeae species. Our results contribute to the novel knowledge of plastid genome evolution in Triticeae. [ABSTRACT FROM AUTHOR]

The polerovirus (family Solemoviridae , genus Polerovirus) genome consists of single-, positive-strand RNA organized in overlapping open reading frames (ORFs) that, in addition to others, code for protein 0 (P0, a gene silencing suppressor), a coat protein (CP, ORF3), and a read-through domain (ORF5) that is fused to the CP to form a CP-read-through (RT) protein. The genus Polerovirus contains twenty-six virus species that infect a wide variety of plants from cereals to cucurbits, to peppers. Poleroviruses are transmitted by a wide range of aphid species in the genera Rhopalosiphum, Stiobion, Aphis , and Myzus. Aphid transmission is mediated both by the CP and by the CP-RT. In viruses, mutational robustness and structural flexibility are necessary for maintaining functionality in genetically diverse sets of host plants and vectors. Under this scenario, within a virus genome, mutations preferentially accumulate in areas that are determinants of host adaptation or vector transmission. In this study, we profiled genomic variation in poleroviruses. Consistent with their multifunctional nature, single-nucleotide variation and selection analyses showed that ORFs coding for P0 and the read-through domain within the CP-RT are the most variable and contain the highest frequency of sites under positive selection. An order/disorder analysis showed that protein P0 is not disordered. In contrast, proteins CP-RT and virus protein genome-linked (VPg) contain areas of disorder. Disorder is a property of multifunctional proteins with multiple interaction partners. The results described here suggest that using contrasting mechanisms, P0, VPg, and CP-RT mediate adaptation to host plants and to vectors and are contributors to the broad host and vector range of poleroviruses. Profiling genetic variation across the polerovirus genome has practical applications in diagnostics, breeding for resistance, and identification of susceptibility genes and contributes to our understanding of virus interactions with their host, vectors, and environment. [ABSTRACT FROM AUTHOR]

MitoLink is a generic, scalable and modular web-based workflow system developed to study genotype-phenotype correlations in human mitochondrial diseases. MitoLink integrates applications for assessment of genomic variation and currently houses genome-wide datasets from GenomeAsia Pilot project, gnomAD, ClinVar and DisGenNet. In this study, a reference list of nearly 3975 proteins (both nuclear and mitochondrial encoded) with mitochondrial function is reported. This protein set is mapped to disease associated variants in the GenomeAsia Pilot Project and DisGenNet and evaluated for pathogenicity as defined by ClinVar. Observations of shared genetic components in potential comorbidities are discussed from gene-disease network in Asian population, however, the platform is generic and can be applied to any population dataset. MitoLink is a unique customized workflow system that allows for systematic storage, extraction, analysis and visualization of genomic variation to understand genotype-phenotype correlations for mitochondrial diseases. Given the modularity of tool and data integration, MitoLink is a scalable system that can accommodate a diverse set of applications linked via standard data structure within the framework of Galaxy. MitoLink is built on FAIR principles and supports creation of reproducible workflows towards understanding genotype-phenotype correlations across several disease phenotypes globally. [ABSTRACT FROM AUTHOR]

To investigate the pattern of chloroplast genome variation in Triticeae, we comprehensively analyzed the indels in protein-coding genes and intergenic sequence, gene loss/pseudonization, intron variation, expansion/contraction in inverted repeat regions, and the relationship between sequence characteristics and chloroplast genome size in 34 monogenomic Triticeae plants. Ancestral genome reconstruction suggests that major length variations occurred in four-stem branches of monogenomic Triticeae followed by independent changes in each genus. It was shown that the chloroplast genome sizes of monogenomic Triticeae were highly variable. The chloroplast genome of Pseudoroegneria, Dasypyrum, Lophopyrum, Thinopyrum, Eremopyrum, Agropyron, Australopyrum, and Henradia in Triticeae had evolved toward size reduction largely because of pseudogenes elimination events and length deletion fragments in intergenic. The Aegilops/Triticum complex, Taeniatherum, Secale, Crithopsis, Herteranthelium, and Hordeum in Triticeae had a larger chloroplast genome size. The large size variation in major lineages and their subclades are most likely consequences of adaptive processes since these variations were significantly correlated with divergence time and historical climatic changes. We also found that several intergenic regions, such as petN–trnC and psbE–petL containing unique genetic information, which can be used as important tools to identify the maternal relationship among Triticeae species. Our results contribute to the novel knowledge of plastid genome evolution in Triticeae.

Liver hepatocellular carcinoma (LIHC) is a primary malignancy, and there is a lack of effective treatment for advanced patients. Although numerous studies exist to reveal the carcinogenic mechanism of LIHC, few studies have integrated multi-omics data to systematically analyze pathogenesis and reveal potential therapeutic targets. Here, we integrated genomic variation data and RNA-seq profiles obtained by high-throughput sequencing to define high- and low-genomic instability samples. The mutational landscape was reported, and the advanced patients of LIHC were characterized by high-genomic instability. We found that the tumor microenvironment underwent metabolic reprograming driven by mutations accumulate to satisfy tumor proliferation and invasion. Further, the co-expression network identifies three mutant long non-coding RNAs as potential therapeutic targets, which can promote tumor progression by participating in specific carcinogenic mechanisms. Then, five potential prognostic markers (RP11-502I4.3, SPINK5, CHRM3, SLC5A12, and RP11-467L13.7) were identified by examining the association of genes and patient survival. By characterizing the immune landscape of LIHC, loss of immunogenicity was revealed as a key factor of immune checkpoint suppression. Macrophages were found to be significantly associated with patient risk scores, and high levels of macrophages accelerated patient mortality. In summary, the mutation-driven mechanism and immune landscape of LIHC revealed by this study will serve precision medicine.

Liver hepatocellular carcinoma (LIHC) is a primary malignancy, and there is a lack of effective treatment for advanced patients. Although numerous studies exist to reveal the carcinogenic mechanism of LIHC, few studies have integrated multi-omics data to systematically analyze pathogenesis and reveal potential therapeutic targets. Here, we integrated genomic variation data and RNA-seq profiles obtained by high-throughput sequencing to define high- and low-genomic instability samples. The mutational landscape was reported, and the advanced patients of LIHC were characterized by high-genomic instability. We found that the tumor microenvironment underwent metabolic reprograming driven by mutations accumulate to satisfy tumor proliferation and invasion. Further, the co-expression network identifies three mutant long non-coding RNAs as potential therapeutic targets, which can promote tumor progression by participating in specific carcinogenic mechanisms. Then, five potential prognostic markers (RP11-502I4.3, SPINK5, CHRM3, SLC5A12 , and RP11-467L13.7) were identified by examining the association of genes and patient survival. By characterizing the immune landscape of LIHC, loss of immunogenicity was revealed as a key factor of immune checkpoint suppression. Macrophages were found to be significantly associated with patient risk scores, and high levels of macrophages accelerated patient mortality. In summary, the mutation-driven mechanism and immune landscape of LIHC revealed by this study will serve precision medicine. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is one of the most common gynecological malignant tumors. The 5-year survival rate remains poor for the advanced and metastatic cervical cancer for the lack of effective treatments. Immunotherapy plays an important role in clinical tumor therapy. Neoantigens derived from tumor-specific somatic mutations are prospective targets for immunotherapy. Hence, the identification of new targets is of great significance for the treatment of advanced and metastatic cervical cancer. In this study, we performed whole-exome sequencing in 70 samples, including 25 cervical intraepithelial neoplasia (CINs) with corresponding blood samples and 10 CCs along with paired adjacent tissues to identify genomic variations and to find the potential neoantigens for CC immunotherapy. Using systematic bioinformatics pipeline, we found that C>T transitions were in both CINs and CCs. In contrast, the number of somatic mutations in CCs was significantly higher than those in CINs (t-test, P = 6.60E-04). Meanwhile, mutational signatures analysis revealed that signature 6 was detected in CIN2, CIN3, and CC, but not in CIN1, while signature 2 was only observed in CCs. Furthermore, PIK3CA, ARHGAP5 and ADGRB1 were identified as potential driver genes in this report, of which ADGRB1 was firstly reported in CC. Based on the genomic variation profiling of CINs and CCs, we identified 2586 potential neoantigens in these patients, of which 45 neoantigens were found in three neoantigen-related databases (TSNAdb, IEDB, and CTDatabase). Our current findings lay a solid foundation for the study of the pathogenesis of CC and the development of neoantigen-targeted immunotherapeutic measures.

Cervical cancer (CC) is one of the most common gynecological malignant tumors. The 5-year survival rate remains poor for the advanced and metastatic cervical cancer for the lack of effective treatments. Immunotherapy plays an important role in clinical tumor therapy. Neoantigens derived from tumor-specific somatic mutations are prospective targets for immunotherapy. Hence, the identification of new targets is of great significance for the treatment of advanced and metastatic cervical cancer. In this study, we performed whole-exome sequencing in 70 samples, including 25 cervical intraepithelial neoplasia (CINs) with corresponding blood samples and 10 CCs along with paired adjacent tissues to identify genomic variations and to find the potential neoantigens for CC immunotherapy. Using systematic bioinformatics pipeline, we found that C>T transitions were in both CINs and CCs. In contrast, the number of somatic mutations in CCs was significantly higher than those in CINs (t-test, P = 6.60E-04). Meanwhile, mutational signatures analysis revealed that signature 6 was detected in CIN2, CIN3, and CC, but not in CIN1, while signature 2 was only observed in CCs. Furthermore, PIK3CA , ARHGAP5 and ADGRB1 were identified as potential driver genes in this report, of which ADGRB1 was firstly reported in CC. Based on the genomic variation profiling of CINs and CCs, we identified 2586 potential neoantigens in these patients, of which 45 neoantigens were found in three neoantigen-related databases (TSNAdb, IEDB, and CTDatabase). Our current findings lay a solid foundation for the study of the pathogenesis of CC and the development of neoantigen-targeted immunotherapeutic measures. [ABSTRACT FROM AUTHOR]

Deciphering the functional impact of genetic variation is required to understand phenotypic diversity and the molecular mechanisms of inherited disease and cancer. While millions of genetic variants are now mapped in genome sequencing projects, distinguishing functional variants remains a major challenge. Protein-coding variation can be interpreted using post-translational modification (PTM) sites that are core components of cellular signaling networks controlling molecular processes and pathways. ActiveDriverDB is an interactive proteo-genomics database that uses more than 260,000 experimentally detected PTM sites to predict the functional impact of genetic variation in disease, cancer and the human population. Using machine learning tools, we prioritize proteins and pathways with enriched PTM-specific amino acid substitutions that potentially rewire signaling networks via induced or disrupted short linear motifs of kinase binding. We then map these effects to site-specific protein interaction networks and drug targets. In the 2021 update, we increased the PTM datasets by nearly 50%, included glycosylation, sumoylation and succinylation as new types of PTMs, and updated the workflows to interpret inherited disease mutations. We added a recent phosphoproteomics dataset reflecting the cellular response to SARS-CoV-2 to predict the impact of human genetic variation on COVID-19 infection and disease course. Overall, we estimate that 16-21% of known amino acid substitutions affect PTM sites among pathogenic disease mutations, somatic mutations in cancer genomes and germline variants in the human population. These data underline the potential of interpreting genetic variation through the lens of PTMs and signaling networks. The open-source database is freely available at www.ActiveDriverDB.org.

When addressing a genomic question, having a reliable and adequate reference genome is of utmost importance. This drives the necessity to refine and customize reference genomes (RGs). Our laboratory has recently developed a strategy, the Perfect Match Genomic Landscape (PMGL), to detect variation between genomes [K. Palacios-Flores et al.. Genetics 208, 1631-1641 (2018)]. The PMGL is precise and sensitive and, in contrast to most currently used algorithms, is nonstatistical in nature. Here we demonstrate the power of PMGL to refine and customize RGs. As a proof-of-concept, we refined different versions of the Saccharomyces cerevisiae RG. We applied the automatic PMGL pipeline to refine the genomes of microorganisms belonging to the three domains of life: the archaea Methanococcus maripaludis and Pyrococcus furiosus; the bacteria Escherichia coli, Staphylococcus aureus, and Bacillus subtilis; and the eukarya Schizosaccharomyces pombe, Aspergillus oryzae, and several strains of Saccharomyces paradoxus. We analyzed the reference genome of the virus SARS-CoV-2 and previously published viral genomes from patients' samples with COVID-19. We performed a mutation-accumulation experiment in E. coli and show that the PMGL strategy can detect specific mutations generated at any desired step of the whole procedure. We propose that PMGL can be used as a final step for the refinement and customization of any haploid genome, independently of the strategies and algorithms used in its assembly. [ABSTRACT FROM AUTHOR]

Bursaphelenchus xylophilus is an emerging pathogenic nematode that is responsible for a devastating epidemic of pine wilt disease worldwide, causing severe ecological damage and economic losses to forestry. Two forms of this nematode have been reported, i.e., with strong and weak virulence, commonly referred as virulent and avirulent strains. However, the pathogenicity-related genes of B. xylophilus are not sufficiently characterized. In this study, to find pathogenesis related genes we re-sequenced and compared genomes of two virulent and two avirulent populations. We identified genes affected by genomic variation, and functional annotation of those genes indicated that some of them might play potential roles in pathogenesis. The performed analysis showed that both avirulent populations differed from the virulent ones by 1576 genes with high impact variants. Demonstration of genetic differences between virulent and avirulent strains will provide effective methods to distinguish these two nematode virulence forms at the molecular level. The reported results provide basic information that can facilitate development of a better diagnosis for B. xylophilus isolates/strains which present different levels of virulence and better understanding of the molecular mechanism involved in the development of the PWD. [ABSTRACT FROM AUTHOR]

Identification of structural variations between individuals is very important for the understanding of phenotype variations and diseases. Despite the existence of dozens of programs for prediction of structural variations, none of them is the golden standard in this field and the results of multiple programs were usually integrated to get more reliable predictions. Annotation and visualization of structural variations are important for the understanding of their functions. However, no program provides these functions currently as far as we are concerned. We report an R package, intansv, which can integrate the predictions of multiple programs as well as annotate and visualize structural variations. The source code and the help manual of intansv is freely available at https://github.com/venyao/intansv and http://www.bioconductor.org/packages/devel/bioc/html/intansv.html.

Abstract Background The genomes of halophilic archaea (haloarchaea) often comprise multiple replicons. Genomic variation in haloarchaea has been linked to viral infection pressure and, in the case of Antarctic communities, can be caused by intergenera gene exchange. To expand understanding of genome variation and biogeography of Antarctic haloarchaea, here we assessed genomic variation between two strains of Halorubrum lacusprofundi that were isolated from Antarctic hypersaline lakes from different regions (Vestfold Hills and Rauer Islands). To assess variation in haloarchaeal populations, including the presence of genomic islands, metagenomes from six hypersaline Antarctic lakes were characterised. Results The sequence of the largest replicon of each Hrr. lacusprofundi strain (primary replicon) was highly conserved, while each of the strains’ two smaller replicons (secondary replicons) were highly variable. Intergenera gene exchange was identified, including the sharing of a type I-B CRISPR system. Evaluation of infectivity of an Antarctic halovirus provided experimental evidence for the differential susceptibility of the strains, bolstering inferences that strain variation is important for modulating interactions with viruses. A relationship was found between genomic structuring and the location of variation within replicons and genomic islands, demonstrating that the way in which haloarchaea accommodate genomic variability relates to replicon structuring. Metagenome read and contig mapping and clustering and scaling analyses demonstrated biogeographical patterning of variation consistent with environment and distance effects. The metagenome data also demonstrated that specific haloarchaeal species dominated the hypersaline systems indicating they are endemic to Antarctica. Conclusion The study describes how genomic variation manifests in Antarctic-lake haloarchaeal communities and provides the basis for future assessments of Antarctic regional and global biogeography of haloarchaea.

• We describe 11 major mutation events which defined five major clades (G 614 , S 84 , V 251 , I 378 and D 392) of globally-circulating viral populations. • We have successfully developed a multiplexed sequencing-based, rapid genotyping protocol for high-throughput classification of major clade types of SARS-CoV-2 in clinical samples. • Several nonsynonymous mutations in the spike protein may have functional consequences: the G clade–defining mutation D614 G located in subdomain 1; the V367 F, G476S and V483A are localised in the receptor binding domain (RBD) of the spike protein. The SARS-CoV-2 pathogen has established endemicity in humans. This necessitates the development of rapid genetic surveillance methodologies to serve as an adjunct with existing comprehensive, albeit though slower, genome sequencing-driven approaches. A total of 21,789 complete genomes were downloaded from GISAID on May 28, 2020 for analyses. We have defined the major clades and subclades of circulating SARS-CoV-2 genomes. A rapid sequencing-based genotyping protocol was developed and tested on SARS-CoV-2-positive RNA samples by next-generation sequencing. We describe 11 major mutations which defined five major clades (G 614 , S 84 , V 251 , I 378 and D 392) of globally circulating viral populations. The clades can specifically identify using an 11-nucleotide genetic barcode. An analysis of amino acid variation in SARS-CoV-2 proteins provided evidence of substitution events in the viral proteins involved in both host entry and genome replication. Globally circulating SARS-CoV-2 genomes could be classified into 5 major clades based on mutational profiles defined by an 11-nucleotide barcode. We have successfully developed a multiplexed sequencing-based, rapid genotyping protocol for high-throughput classification of major clade types of SARS-CoV-2 in clinical samples. This barcoding strategy will be required to monitor decreases in genetic diversity as treatment and vaccine approaches become widely available. [ABSTRACT FROM AUTHOR]

Background: Lotus (Nelumbo nucifera) is an aquatic plant with important agronomic, horticulture, art and religion values. It was the basal eudicot species occupying a critical phylogenetic position in flowering plants. After the domestication for thousands of years, lotus has differentiated into three cultivated types -flower lotus, seed lotus and rhizome lotus. Although the phenotypic and genetic differentiations based on molecular markers have been reported, the variation on whole-genome level among the different lotus types is still ambiguous. Results: In order to reveal the evolution and domestication characteristics of lotus, a total of 69 lotus accessions were selected, including 45 cultivated accessions, 22 wild sacred lotus accessions, and 2 wild American lotus accessions. With Illumina technology, the genomes of these lotus accessions were resequenced to > 13× raw data coverage. On the basis of these genomic data, 25 million single-nucleotide polymorphisms (SNPs) were identified in lotus. Population analysis showed that the rhizome and seed lotus were monophyletic and genetically homogeneous, whereas the flower lotus was biphyletic and genetically heterogeneous. Using population SNP data, we identified 1214 selected regions in seed lotus, 95 in rhizome lotus, and 37 in flower lotus. Some of the genes in these regions contributed to the essential domestication traits of lotus. The selected genes of seed lotus mainly affected lotus seed weight, size and nutritional quality. While the selected genes were responsible for insect resistance, antibacterial immunity and freezing and heat stress resistance in flower lotus, and improved the size of rhizome in rhizome lotus, respectively. Conclusions: The genome differentiation and a set of domestication genes were identified from three types of cultivated lotus- flower lotus, seed lotus and rhizome lotus, respectively. Among cultivated lotus, flower lotus showed the greatest variation. The domestication genes may show agronomic importance via enhancing insect resistance, improving seed weight and size, or regulating lotus rhizome size. The domestication history of lotus enhances our knowledge of perennial aquatic crop evolution, and the obtained dataset provides a basis for future genomics-enabled breeding. [ABSTRACT FROM AUTHOR]

Abstract Background Monozygotic twins are valuable in assessing the genetic vs environmental contribution to diseases. In the era of complete genome sequences, they allow identification of mutational mechanisms and specific genes and pathways that offer predisposition to the development of complex diseases including schizophrenia. Methods We sequenced the complete genomes of two pairs of monozygotic twins discordant for schizophrenia (MZD), including one representing a family tetrad. The family specific complete sequences have allowed identification of post zygotic mutations between MZD genomes. It allows identification of affected genes including relevant network and pathways that may account for the diseased state in pair specific patient. Results We found multiple twin specific sequence differences between co-twins that included small nucleotides [single nucleotide variants (SNV), small indels and block substitutions], copy number variations (CNVs) and structural variations. The genes affected by these changes belonged to a number of canonical pathways, the most prominent ones are implicated in schizophrenia and related disorders. Although these changes were found in both twins, they were more frequent in the affected twin in both pairs. Two specific pathway defects, glutamate receptor signaling and dopamine feedback in cAMP signaling pathways, were uniquely affected in the two patients representing two unrelated families. Conclusions We have identified genome-wide post zygotic mutations in two MZD pairs affected with schizophrenia. It has allowed us to use the threshold model and propose the most likely cause of this disease in the two patients studied. The results support the proposition that each schizophrenia patient may be unique and heterogeneous somatic de novo events may contribute to schizophrenia threshold and discordance of the disease in monozygotic twins.

Although genome sequencing has become increasingly popular, the simulation of individual genomes is still important. This is because sequencing a large number of individual genomes is costly and genome data with extreme and boundary conditions, such as fatal genetic defects, are difficult to obtain. Privacy and legal barriers also prevent many applications of real data. Large sequencing projects in recent years have provided a deeper understanding of the human genome. However, there is a lack of tools to leverage known data to simulate personal genomes as real as possible. Here, we designed and developed PGsim, a comprehensive and highly customizable individual genome simulator, that fully uses existing knowledge, such as variant allele frequencies in global or world main populations, mutation probability differences between protein-coding regions and non-coding regions, transition/transversion (Ti/Tv) ratios, Indel incidence, Indel length distribution, structural variation sites, and pathogenic mutation sites. Users can flexibly control the proportion and quantity of known variants, common variants, novel variants in both coding and non-coding regions, and special variants through detailed parameter settings. To ensure that the simulated personal genome has sufficient randomness, PGsim makes the generated variants more real and reliable in terms of variant distribution, proportion, and population characteristics. PGsim is able to employ a huge volume database as background data to simulate personal genomes and does not require SQL database support. Users can easily change the variant databases used as needed. As a Perl script, there is no obstacle to running PGsim on any version of the MAC OS or Linux systems, and no libraries, packages, interpreters, compilers, or other dependencies need to be installed in advance. The PGsim tool is publicly available at https://github.com/lrjuan/PGsim.

Candida glabrata is an opportunistic fungal pathogen that currently ranks as the second most common cause of candidiasis. Although the mechanisms underlying virulence and drug resistance in C. glabrata are now starting to be elucidated, we still lack a good understanding of how this yeast adapts during the course of an infection. Outstanding questions are whether the observed genomic plasticity of C. glabrata plays a role during infection, or what levels of genetic variation exist within an infecting clonal population. To shed light onto the genomic variation within infecting C. glabrata populations, we compared the genomes of 11 pairs and one trio of serial clinical isolates, each obtained from a single patient. Our results provide a catalog of genetic variations existing within clonal infecting isolates, and reveal an enrichment of non-synonymous changes in genes encoding cell-wall proteins. Genetic variation and the presence of non-synonymous mutations and copy number variations accumulated within the host, suggest that clonal populations entail a non-negligible level of genetic variation that may reflect selection processes that occur within the human body. As we show here, these genomic changes can underlie phenotypic differences in traits that are relevant for infection.

Among the Hevea species, rubber tree ( Hevea brasiliensis ) is the most important source of natural rubber. In previous studies, we sequenced the complete nuclear and chloroplast genomes of Hevea species, providing an invaluable resource for studying their phylogeny, disease resistance, and breeding. However, given that plant mitochondrial genomes are more complex and more difficult to assemble than that of the other organelles, little is known about their mitochondrial genome, which limits the comprehensive understanding of Hevea genomic evolution. In this study, we sequenced and assembled the mitochondrial genomes of four Hevea species. The four mitochondrial genomes had consistent GC contents, codon usages and AT skews. However, there were significant differences in the genome lengths and sequence repeats. Specifically, the circular mitochondrial genomes of the four Hevea species ranged from 935,732 to 1,402,206 bp, with 34-35 unique protein-coding genes, 35-38 tRNA genes, and 6-13 rRNA genes. In addition, there were 17,294-46,552 bp intergenomic transfer fragments between the chloroplast and mitochondrial genomes, consisting of eight intact genes ( psaA, rrn16S, tRNA-Val, rrn5S, rrn4.5S, tRNA-Arg, tRNA-Asp , and tRNA-Asn ), intergenic spacer regions and partial gene sequences. The evolutionary position of Hevea species, crucial for understanding its adaptive strategies and relation to other species, was verified by phylogenetic analysis based on the protein-coding genes in the mitochondrial genomes of 21 Malpighiales species. The findings from this study not only provide valuable insights into the structure and evolution of the Hevea mitochondrial genome but also lay the foundation for further molecular, evolutionary studies, and genomic breeding studies on rubber tree and other Hevea species, thereby potentially informing conservation and utilization strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Niu, Gao and Liu.)

Knowledge of ploidy level and genome size in a germplasm collection is critical before studying genetic diversification of different environmental range in grasses and other plants. We assessed the geographic patterns in ploidy level and genome size of 216 individuals of Cynodon dactylon (L.) Pers. (common bermudagrass) by flow cytometry of accessions sampled from 16 geographic sites along a latitudinal gradient from 22°35′ N to 36°18′ N across China. Flow cytometry histograms combined with mitotic chromosome observations results show that tetraploids were the most frequent ploidy level, constituting 44.91% of all individuals. Nuclear DNA contents were 2.384, 2.419, 2.437, 2.873 and 3.288 pg/2C for the diploid, triploid, tetraploid, pentaploid and hexaploid, respectively. Higher proportions of polyploid individuals were observed within populations at the highest and lowest latitudes. In addition, monoploid genome size of C. dactylon progressively increased with increasing ploidy level. Temperature and precipitation had the influence on ploidy level for all the sites. The relationship between ploidy level and geographic distribution for C. dactylon will facilitate the utilization of this species for biological and genetic research. [ABSTRACT FROM AUTHOR]

• HPV16 genomes display variation in individual cervical samples. • Emerging genomic minor nucleotide variations in persistent HPV16 infections. • Frequent T > C mutational profiles were identified. • Minor nucleotide variations previously associated with high grade lesions (CIN3+) detected. Chronic infections by one of the oncogenic human papillomaviruses (HPVs) are responsible for near 5% of the global cancer burden and HPV16 is the type most often found in cancers. HPV genomes display unexpected levels of variation when deep-sequenced. Minor nucleotide variations (MNVs) may reveal HPV genomic instability and HPV-related carcinogenic transformation of host cells. The objective of this study was to investigate HPV16 genome variation at the minor variant level on persisting HPV16 cervical infections from a population of young Dutch women. 15 HPV16 infections were sequenced using a whole-HPV genome deep sequencing protocol (TaME-seq). One infection was followed over a three-year period, eight were followed over a two-year period, three were followed over a one-year period and three infections had a single sampling point. Using a 1% variant frequency cutoff, we find on average 48 MNVs per HPV16 genome and 1717 MNVs in total when sequencing coverage was >100 ×. We find the transition mutation T > C to be the most common, in contrast to other studies detecting APOBEC-related C > T mutation profiles in pre-cancerous and cancer samples. Our results suggest that the relative mutagenic footprint of HPV16 genomes may differ between the infections in this study and transforming lesions. In addition, we identify a number of MNVs that have previously been associated with higher incidence of high-grade lesions (CIN3+) in a population study. These findings may provide a starting point for future studies exploring causality between emerging HPV minor genomic variants and cancer development. [ABSTRACT FROM AUTHOR]