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Genome-wide association studies (GWAS) have now been conducted for hundreds of phenotypes of relevance to human health. Many such GWAS involve multiple closely-related phenotypes collected on the same samples. However, the vast majority of these GWAS have been analyzed using simple univariate analyses, which consider one phenotype at a time. This is despite the fact that, at least in simulation experiments, multivariate analyses have been shown to be more powerful at detecting associations. Here, we conduct multivariate association analyses on 13 different publicly-available GWAS datasets that involve multiple closely-related phenotypes. These data include large studies of anthropometric traits (GIANT), plasma lipid traits (GlobalLipids), and red blood cell traits (HaemgenRBC). Our analyses identify many new associations (433 in total across the 13 studies), many of which replicate when follow-up samples are available. Overall, our results demonstrate that multivariate analyses can help make more effective use of data from both existing and future GWAS. [ABSTRACT FROM AUTHOR]

The fragmentation of habitats and hunting have impacted the Asian woolly-necked stork (Ciconia episcopus), leading to a serious risk of extinction in Thailand. Programs of active captive breeding, together with careful genetic monitoring, can play an important role in facilitating the creation of source populations with genetic variability to aid the recovery of endangered species. Here, the genetic diversity and population structure of 86 Asian woolly-necked storks from three captive breeding programs [Khao Kheow Open Zoo (KKOZ) comprising 68 individuals, Nakhon Ratchasima Zoo (NRZ) comprising 16 individuals, and Dusit Zoo (DSZ) comprising 2 individuals] were analyzed using 13 microsatellite loci, to aid effective conservation management. Inbreeding and an extremely low effective population size (Ne) were found in the KKOZ population, suggesting that deleterious genetic issues had resulted from multiple generations held in captivity. By contrast, a recent demographic bottleneck was observed in the population at NRZ, where the ratio of Ne to abundance (N) was greater than 1. Clustering analysis also showed that one subdivision of the KKOZ population shared allelic variability with the NRZ population. This suggests that genetic drift, with a possible recent and mixed origin, occurred in the initial NRZ population, indicating historical transfer between captivities. These captive stork populations require improved genetic variability and a greater population size, which could be achieved by choosing low-related individuals for future transfers to increase the adaptive potential of reintroduced populations. Forward-in-time simulations such as those described herein constitute the first step in establishing an appropriate source population using a scientifically managed perspective for an in situ and ex situ conservation program in Thailand. [ABSTRACT FROM AUTHOR]

The Mediterranean sesame core collection contains agro-morphologically superior sesame accessions from geographically diverse regions in four continents. In the present investigation, the genetic diversity and population structure of this collection was analyzed with 5292 high-quality SNPs discovered by double-digest restriction site associated DNA (ddRAD) sequencing, a cost-effective and flexible next-generation sequencing method. The genetic distance between pairs of accessions varied from 0.023 to 0.524. The gene diversity was higher in accessions from Asia than from America, Africa, and Europe. The highest genetic differentiation was observed between accessions collected from America and Europe. Structure analysis showed the presence of three subpopulations among the sesame accessions, and only six accessions were placed in an admixture group. Phylogenetic tree and principal coordinate analysis clustered the accessions based on their countries of origin. However, no clear division was evident among the sesame accessions with regard to their continental locations. This result was supported by an AMOVA analysis, which revealed a genetic variation among continental groups of 5.53% of the total variation. The large number of SNPs clearly indicated that the Mediterranean sesame core collection is a highly diverse genetic resource. The collection can be exploited by breeders to select appropriate accessions that will provide high genetic gain in sesame improvement programs. The high-quality SNP data generated here should also be used in genome-wide association studies to explore qualitative trait loci and SNPs related to economically and agronomically important traits in sesame. [ABSTRACT FROM AUTHOR]

Calibration of the molecular rate is one of the major challenges in marine population genetics. Although the use of an appropriate evolutionary rate is crucial in exploring population histories, calibration of the rate is always difficult because fossil records and geological events are rarely applicable for rate calibration. The acceleration of the evolutionary rate for recent coalescent events (or more simply, the time dependency of the molecular clock) is also a problem that can lead to overestimation of population parameters. Calibration of demographic transition (CDT) is a rate calibration technique that assumes a post-glacial demographic expansion, representing one of the most promising approaches for dealing with these potential problems in the rate calibration. Here, we demonstrate the importance of using an appropriate evolutionary rate, and the power of CDT, by using populations of the sandy beach amphipod Haustorioides japonicus along the Japanese coast of the northwestern Pacific Ocean. Analysis of mitochondrial sequences found that the most peripheral population in the Pacific coast of northeastern Honshu Island (Tohoku region) is genetically distinct from the other northwestern Pacific populations. By using the two-epoch demographic model and rate of temperature change, the evolutionary rate was modeled as a log-normal distribution with a median rate of 2.2%/My. The split-time of the Tohoku population was subsequently estimated to be during the previous interglacial period by using the rate distribution, which enables us to infer potential causes of the divergence between local populations along the continuous Pacific coast of Japan. [ABSTRACT FROM AUTHOR]

A number of studies carried out since the early ‘70s has investigated the effects of isolation on genetic variation within and among human populations in diverse geographical contexts. However, no extensive analysis has been carried out on the heterogeneity among genomes within isolated populations. This issue is worth exploring since events of recent admixture and/or subdivision could potentially disrupt the genetic homogeneity which is to be expected when isolation is prolonged and constant over time. Here, we analyze literature data relative to 87,815 autosomal single-nucleotide polymorphisms, which were obtained from a total of 28 European populations. Our results challenge the traditional paradigm of population isolates as structured as genetically (and genomically) uniform entities. In fact, focusing on the distribution of variance of intra-population diversity measures across individuals, we show that the inter-individual heterogeneity of isolated populations is at least comparable to the open ones. More in particular, three small and highly inbred isolates (Sappada, Sauris and Timau in Northeastern Italy) were found to be characterized by levels of inter-individual heterogeneity largely exceeding that of all other populations, possibly due to relatively recent events of genetic introgression. Finally, we propose a way to monitor the effects of inter-individual heterogeneity in disease-gene association studies. [ABSTRACT FROM AUTHOR]

The impacts of invertebrate RNA virus population dynamics on virulence and infection outcomes are poorly understood. Deformed wing virus (DWV), the main viral pathogen of honey bees, negatively impacts bee health, which can lead to colony death. Despite previous reports on the reduction of DWV diversity following the arrival of the parasitic mite Varroa destructor, the key DWV vector, we found high genetic diversity of DWV in infested United States honey bee colonies. Phylogenetic analysis showed that divergent US DWV genotypes are of monophyletic origin and were likely generated as a result of diversification after a genetic bottleneck. To investigate the population dynamics of this divergent DWV, we designed a series of novel infectious cDNA clones corresponding to coexisting DWV genotypes, thereby devising a reverse-genetics system for an invertebrate RNA virus quasispecies. Equal replication rates were observed for all clone-derived DWV variants in single infections. Surprisingly, individual clones replicated to the same high levels as their mixtures and even the parental highly diverse natural DWV population, suggesting that complementation between genotypes was not required to replicate to high levels. Mixed clone–derived infections showed a lack of strong competitive exclusion, suggesting that the DWV genotypes were adapted to coexist. Mutational and recombination events were observed across clone progeny, providing new insights into the forces that drive and constrain virus diversification. Accordingly, our results suggest that Varroa influences DWV dynamics by causing an initial selective sweep, which is followed by virus diversification fueled by negative frequency-dependent selection for new genotypes. We suggest that this selection might reflect the ability of rare lineages to evade host defenses, specifically antiviral RNA interference (RNAi). In support of this hypothesis, we show that RNAi induced against one DWV strain is less effective against an alternate strain from the same population. [ABSTRACT FROM AUTHOR]

The green turtle (Chelonia mydas) is a globally distributed marine species whose evolutionary history has been molded by geological events and oceanographic and climate changes. Divergence between Atlantic and Pacific clades has been associated with the uplift of the Panama Isthmus, and inside the Pacific region, a biogeographic barrier located west of Hawaii has restricted the gene flow between Central/Eastern and Western Pacific populations. We investigated the carapace shape of C. mydas from individuals of Atlantic, Eastern Pacific, and Western Pacific genetic lineages using geometric morphometrics to evaluate congruence between external morphology and species’ phylogeography. Furthermore, we assessed the variation of carapace shape according to foraging grounds. Three morphologically distinctive groups were observed which aligned with predictions based on the species’ lineages, suggesting a substantial genetic influence on carapace shape. Based on the relationship between this trait and genetic lineages, we propose the existence of at least three distinct morphotypes of C. mydas. Well-defined groups in some foraging grounds (Galapagos, Costa Rica and New Zealand) may suggest that ecological or environmental conditions in these sites could also be influencing carapace shape in C. mydas. Geometric morphometrics is a suitable tool to differentiate genetic lineages in this cosmopolitan marine species. Consequently, this study opens new possibilities to explore and test ecological and evolutionary hypotheses in species with wide morphological variation and broad geographic distribution range. [ABSTRACT FROM AUTHOR]

Non-uniform rates of morphological evolution and evolutionary increases in organismal complexity, captured in metaphors like “adaptive zones”, “punctuated equilibrium” and “blunderbuss patterns”, require more elaborate explanations than a simple gradual accumulation of mutations. Here we argue that non-uniform evolutionary increases in phenotypic complexity can be caused by a threshold-like response to growing ecological pressures resulting from evolutionary diversification at a given level of complexity. Acquisition of a new phenotypic feature allows an evolving species to escape this pressure but can typically be expected to carry significant physiological costs. Therefore, the ecological pressure should exceed a certain level to make such an acquisition evolutionarily successful. We present a detailed quantitative description of this process using a microevolutionary competition model as an example. The model exhibits sequential increases in phenotypic complexity driven by diversification at existing levels of complexity and a resulting increase in competitive pressure, which can push an evolving species over the barrier of physiological costs of new phenotypic features. [ABSTRACT FROM AUTHOR]

Lutzomyia longipalpis is the main vector of Leishmania infantum, the causative agent of visceral leishmaniasis in the Neotropical realm. Its taxonomic status has been widely discussed once it encompasses a complex of species. The knowledge about the genetic structure of insect vector populations helps the elucidation of components and interactions of the disease ecoepidemiology. Thus, the objective of this study was to genotypically analyze populations of the Lu. longipalpis complex from a macrogeographic perspective using Next Generation Sequencing. Polymorphism analysis of three molecular markers was used to access the levels of population genetic structure among nine different populations of sand flies. Illumina Amplicon Sequencing Protocol® was used to identify possible polymorphic sites. The library was sequenced on paired-end Illumina MiSeq platform. Significant macrogeographical population differentiation was observed among Lu. longipalpis populations via PCA and DAPC analyses. Our results revealed that populations of Lu. longipalpis from the nine municipalities were grouped into three clusters. In addition, it was observed that the levels of Lu. longipalpis population structure could be associated with distance isolation. This new sequencing method allowed us to study different molecular markers after a single sequencing run, and to evaluate population and inter-species differences on a macrogeographic scale. [ABSTRACT FROM AUTHOR]

Classical crop models have been developed to predict crop yield and quality, and they are based on physiological and environmental inputs. After molecular discoveries, models should integrate genetic variation to allow predictions that are more genotype-dependent. An interesting approach, Quantitative Trait Locus (QTL)-based ecophysiological modeling, has shown promising results for the design of ideotypes that are adapted to biotic and abiotic stresses, but there are still limitations to attaining a fully integrated model. The aim of this case study is to clarify the impact of choosing different model equations (closely related and with different numbers of parameters) and optimization methods on the detection of QTLs controlling the parameters of crop growth. Different growth equations were parameterized based on a genetic population by following different approaches. The correlations between parameters were analyzed, and two different strategies were adopted to address the correlation issue. QTL analysis was performed on the optimized values of the parameters of the growth equations and on the observed dry mass (DM) data to validate the QTLs detected. Overall, models and strategies resulted in different QTLs being detected. Similar LOD profiles but with peaks of different heights were observed, some of which were significant, resulting in different numbers of QTLs. In some cases, peaks had slightly different positions or were absent. Even closely related growth models led to the detection of different QTLs. The goodness of fit and complexity of the growth models were found to be insufficient to select the best model. Calculating parameters independently of observed data may not be a good strategy, whereas setting parameters independent of the genotype is recommended. Given the large-scale global optimization problem and the strong correlations between parameters, the two algorithms tested showed poor performance. Currently, the lack of effective algorithms is the main obstacle to answering the question posed. The authors therefore suggest testing different model formulations and comparing the QTLs detected before choosing the best formulation to use in an ecophysiological modeling approach based on QTLs. [ABSTRACT FROM AUTHOR]

HIV-1 gene expression is regulated by host and viral factors that interact with viral motifs and is influenced by proviral integration sites. Here, expression variation among integrants was followed for hundreds of individual proviral clones within polyclonal populations throughout successive rounds of virus and cultured cell replication, with limited findings using CD4+ cells from donor blood consistent with observations in immortalized cells. Tracking clonal behavior by proviral “zip codes” indicated that mutational inactivation during reverse transcription was rare, while clonal expansion and proviral expression states varied widely. By sorting for provirus expression using a GFP reporter in the nef open reading frame, distinct clone-specific variation in on/off proportions were observed that spanned three orders of magnitude. Tracking GFP phenotypes over time revealed that as cells divided, their progeny alternated between HIV transcriptional activity and non-activity. Despite these phenotypic oscillations, the overall GFP+ population within each clone was remarkably stable, with clones maintaining clone-specific equilibrium mixtures of GFP+ and GFP- cells. Integration sites were analyzed for correlations between genomic features and the epigenetic phenomena described here. Integrants inserted in the sense orientation of genes were more frequently found to be GFP negative than those in the antisense orientation, and clones with high GFP+ proportions were more distal to repressive H3K9me3 peaks than low GFP+ clones. Clones with low frequencies of GFP positivity appeared to expand more rapidly than clones for which most cells were GFP+, even though the tested proviruses were Vpr-. Thus, much of the increase in the GFP- population in these polyclonal pools over time reflected differential clonal expansion. Together, these results underscore the temporal and quantitative variability in HIV-1 gene expression among proviral clones that are conferred in the absence of metabolic or cell-type dependent variability, and shed light on cell-intrinsic layers of regulation that affect HIV-1 population dynamics. [ABSTRACT FROM AUTHOR]

The recent expansion of the invasive lionfish throughout the Western Hemisphere is one of the most extensively studied aquatic invasions. Molecular studies have improved our understanding of larval dispersal, connectivity, and biogeographical barriers among lionfish populations, but none have included Mexican localities, an important area for the larval dispersal of Pterois volitans through the Western Caribbean and the Gulf of Mexico. Here, we present a genetic analysis of lionfishes collected along Mexican coasts, examining their connectivity with other Caribbean localities (Belize, Cuba, Puerto Rico) and the role of ocean currents on population structure. We collected 213 lionfish samples from seven locations comprising four countries. To evaluate genetic structure, mitochondrial control region and nuclear inter-simple sequence repeat markers were used. We found that lionfish collected along Mexican coasts show a similar haplotype composition (H02 followed by H01 and H04) to other Caribbean locations, and the H03 rare haplotype was not found. Haplotype composition in the southwest Gulf of Mexico suggests a discontinuity between the southern and northern areas of the Gulf of Mexico. The southern area clustered more strongly to the Caribbean region, and this is supported by the complexity of water circulation in the semi-enclosed region of the Gulf of Mexico. Mitochondrial genetic diversity parameters show small values, whereas nuclear markers produce medium to high values. Only nuclear markers highlighted significant genetic differentiation between the southwest Gulf of Mexico and Caribbean region, confirming a phylogeographic break between both regions. Separate analysis of Caribbean locations indicates restricted larval exchange between southern and northern regions of the Mesoamerican Barrier Reef System, potentially in response to regional oceanographic circulation. [ABSTRACT FROM AUTHOR]

Background: The mitochondrial genome encodes for thirty-seven proteins, among them thirteen are essential for the oxidative phosphorylation (OXPHOS) system. Inherited variation in mitochondrial genes may influence cancer development through changes in mitochondrial proteins, altering the OXPHOS process and promoting the production of reactive oxidative species. Methods: To investigate the association between mitochondrial genetic variation and breast cancer risk, we tested 314 mitochondrial SNPs (mtSNPs), capturing four complexes of the mitochondrial OXPHOS pathway and mtSNP groupings for rRNA and tRNA, in 2,723 breast cancer cases and 3,260 controls from the Multiethnic Cohort Study. Results: We examined the collective set of 314 mtSNPs as well as subsets of mtSNPs grouped by mitochondrial OXPHOS pathway, complexes, and genes, using the sequence kernel association test and adjusting for age, sex, and principal components of global ancestry. We also tested haplogroup associations using unconditional logistic regression and adjusting for the same covariates. Stratified analyses were conducted by self-reported maternal race/ethnicity. No significant mitochondrial OXPHOS pathway, gene, and haplogroup associations were observed in African Americans, Asian Americans, Latinos, and Native Hawaiians. In European Americans, a global test of all genetic variants of the mitochondrial genome identified an association with breast cancer risk (P = 0.017, q = 0.102). In mtSNP-subset analysis, the gene MT-CO2 (P = 0.001, q = 0.09) in Complex IV (cytochrome c oxidase) and MT-ND2 (P = 0.004, q = 0.19) in Complex I (NADH dehydrogenase (ubiquinone)) were significantly associated with breast cancer risk. Conclusions: In summary, our findings suggest that collective mitochondrial genetic variation and particularly in the MT-CO2 and MT-ND2 may play a role in breast cancer risk among European Americans. Further replication is warranted in larger populations and future studies should evaluate the contribution of mitochondrial proteins encoded by both the nuclear and mitochondrial genomes to breast cancer risk. [ABSTRACT FROM AUTHOR]

As a leading cause of neonatal sepsis, Streptococcus agalactiae, commonly known as Group B Streptococcus, is a major neonatal pathogen. Current global screening practices employ risk- or culture-based protocols for detection of these organisms. In Western Australia (WA), universal culture-based screening is provided, with subsequent intrapartum antibiotic prophylaxis for all S. agalactiae-positive women during labour. Widespread antibiotic exposure is not ideal and this is one of the factors driving development of vaccines against S. agalactiae. Vaccine candidates have focused on the capsule, surface proteins and pilus types, however, capsule serotypes are known to vary geographically. The aim of this study was to use genome sequencing to gain an understanding of the circulating genotypes in WA, and to assess variations in the associated gene pools. We sequenced 141 antenatal carriage (vaginal/rectal) isolates and 10 neonatal invasive disease isolates from WA. Based on the global PubMLST database, the 151 strains were characterised into 30 sequence types, with clustering of these mainly into clonal complexes 1, 12, 17, 19 and 23. Of the genes encoding eleven surface proteins that were analysed, the most prevalent were fbp, lmb and scpB which were present in ≥ 98% of isolates. A cluster of non-haemolytic isolates, one of which was a neonatal invasive disease isolate, appeared to lack the entire cyl locus. Admixture analysis of population structure revealed evidence of genetic transfer among the WA isolates across structural groups. When compared against the PubMLST S. agalactiae data, WA isolates showed high levels of strain diversity with minimal apparent clustering. This is the first whole genome sequence study of WA S. agalactiae isolates and also represents the first addition of Australian isolate data to PubMLST. This report provides insight into the distribution and diversity of vaccine targets of S. agalactiae within Western Australia, indicating that the most appropriate capsular vaccine for this population would be the proposed pentavalent (Cps Ia, Ib, II, III and V) preparation, whilst vaccines targeting surface proteins should ideally utilise Fbp, Lmb and/or ScpB. [ABSTRACT FROM AUTHOR]

Genetic divergence is impacted by many factors, including phylogenetic history, gene flow, genetic drift, and divergent selection. Rotifers are an important component of aquatic ecosystems, and genetic variation is essential to their ongoing adaptive diversification and local adaptation. In addition to coding sequence divergence, variation in gene expression may relate to variable heat tolerance, and can impose ecological barriers within species. Temperature plays a significant role in aquatic ecosystems by affecting species abundance, spatio-temporal distribution, and habitat colonization. Recently described (formerly cryptic) species of the Brachionus calyciflorus complex exhibit different temperature tolerance both in natural and in laboratory studies, and show that B. calyciflorus sensu stricto (s.s.) is a thermotolerant species. Even within B. calyciflorus s.s., there is a tendency for further temperature specializations. Comparison of expressed genes allows us to assess the impact of stressors on both expression and sequence divergence among disparate populations within a single species. Here, we have used RNA-seq to explore expressed genetic diversity in B. calyciflorus s.s. in two mitochondrial DNA lineages with different phylogenetic histories and differences in thermotolerance. We identify a suite of candidate genes that may underlie local adaptation, with a particular focus on the response to sustained high or low temperatures. We do not find adaptive divergence in established candidate genes for thermal adaptation. Rather, we detect divergent selection among our two lineages in genes related to metabolism (lipid metabolism, metabolism of xenobiotics). [ABSTRACT FROM AUTHOR]

Soil salinity is a major threat to crop production worldwide. The global climate change is further accelerating the process of soil salinization, particularly in dry areas of the world. Increasing genetic variability of currently used wheat varieties by introgression of exotic alleles/genes from related progenitors’ species in breeding programs is an efficient approach to overcome limitations due to the absence of valuable genetic diversity in elite cultivars. Synthetic hexaploid wheat (SHW) is widely regarded as donor of favourable exotic alleles to improve tolerance against biotic and abiotic stresses such as salinity stress. In this study, synthetic backcross lines (SBLs) winter wheat population “Z86”, derived from crosses involving synthetic hexaploid wheat Syn86L with German elite winter wheat cultivar Zentos, was evaluated for salinity tolerance at different developmental stages under controlled and field conditions in three growing seasons. High genetic variability was detected across the SBLs and their parents at various growth stages under controlled as well as under salt stress field trials. Greater performance of Zentos over Syn86L was detected at germination stage across all salt treatments and with respect to shoot dry weight (SDW) and root dry weight (RDW) at seedling stage. Whereas for the root length (RL) and the shoot length (SL) Syn86L surpassed the elite cultivar and most of the progenies. Our experiments revealed for almost all traits that some genotypes among the SBLs showed higher performance than their parents. Furthermore, positive transgressive segregations were detected among the SBLs for germination at high salinity levels, as well as for RDW and SDW at seedling stage. Therefore, the studied Z86 population is a suitable population for assessment of salinity stress on morphological and physiological traits at different plant growth stages. The identified SBLs provide a valuable source for genetic gain through recombination of superior alleles that can be directly applied in breeding programs for efficiently breeding cultivars with improved salinity tolerance and desired agronomic traits. [ABSTRACT FROM AUTHOR]

Iran, despite its size, geographic location and past cultural influence, has largely been a blind spot for human population genetic studies. With only sparse genetic information on the Iranian population available, we pursued its genome-wide and geographic characterization based on 1021 samples from eleven ethnic groups. We show that Iranians, while close to neighboring populations, present distinct genetic variation consistent with long-standing genetic continuity, harbor high heterogeneity and different levels of consanguinity, fall apart into a cluster of similar groups and several admixed ones and have experienced numerous language adoption events in the past. Our findings render Iran an important source for human genetic variation in Western and Central Asia, will guide adequate study sampling and assist the interpretation of putative disease-implicated genetic variation. Given Iran’s internal genetic heterogeneity, future studies will have to consider ethnic affiliations and possible admixture. [ABSTRACT FROM AUTHOR]

The hoverfly, Eupeodes corollae, is a worldwide natural enemy of aphids and a plant pollinator. To provide insights into the biology of this species, we examined its population genetic structure by obtaining 1.15-GB random genomic sequences using next-generation sequencing and developing genome-wide microsatellite markers. A total of 79,138 microsatellite loci were initially isolated from the genomic sequences; after strict selection and further testing of 40 primer pairs in eight individuals, 24 polymorphic microsatellites with high amplification rates were developed. These microsatellites were used to examine the population genetic structure of 96 individuals from four field populations collected across southern to northern China. The number of alleles per locus ranged from 5 to 13 with an average of 8.75; the observed and expected heterozygosity varied from 0.235 to 0.768 and from 0.333 to 0.785, respectively. Population genetic structure analysis showed weak genetic differentiation among the four geographical populations of E. corollae, suggesting a high rate of gene flow reflecting likely widespread migration of E. corollae in China. [ABSTRACT FROM AUTHOR]

Fin whales (Balaenoptera physalus) and blue whales (B. musculus) are the two largest species on Earth and are widely distributed across the world’s oceans. Hybrids between these species appear to be relatively widespread and have been reported in both the North Atlantic and North Pacific; they are also relatively common, and have been proposed to occur once in every thousand fin whales. However, despite known hybridization, fin and blue whales are not sibling species. Rather, the closest living relative of fin whales are humpback whales (Megaptera novaeangliae). To improve the quality of fin whale data available for analysis, we assembled and annotated a fin whale nuclear genome using in-silico mate pair libraries and previously published short-read data. Using this assembly and genomic data from a humpback, blue, and bowhead whale, we investigated whether signatures of introgression between the fin and blue whale could be found. We find no signatures of contemporary admixture in the fin and blue whale genomes, although our analyses support ancestral gene flow between the species until 2.4–1.3 Ma. We propose the following explanations for our findings; i) fin/blue whale hybridization does not occur in the populations our samples originate from, ii) contemporary hybrids are a recent phenomenon and the genetic consequences have yet to become widespread across populations, or iii) fin/blue whale hybrids are under large negative selection, preventing them from backcrossing and contributing to the parental gene pools. [ABSTRACT FROM AUTHOR]

The Roma population is the largest transnational ethnic minority in Europe, characterized by a linguistic, cultural and historical heterogeneity. Comparative linguistics and genetic studies have placed the origin of European Roma in the Northwest of India. After their migration across Persia, they entered into the Balkan Peninsula, from where they spread into Europe, arriving in the Iberian Peninsula in the 15th century. Their particular demographic history has genetic implications linked to rare and common diseases. However, the South Asian source of the proto-Roma remains still untargeted and the West Eurasian Roma component has not been yet deeply characterized. Here, in order to describe both the South Asian and West Eurasian ancestries, we analyze previously published genome-wide data of 152 European Roma and 34 new Iberian Roma samples at a fine-scale and haplotype-based level, with special focus on the Iberian Roma genetic substructure. Our results suggest that the putative origin of the proto-Roma involves a Punjabi group with low levels of West Eurasian ancestry. In addition, we have identified a complex West Eurasian component (around 65%) in the Roma, as a result of the admixture events occurred with non-proto-Roma populations between 1270–1580. Particularly, we have detected the Balkan genetic footprint in all European Roma, and the Baltic and Iberian components in the Northern and Western Roma groups, respectively. Finally, our results show genetic substructure within the Iberian Roma, with different levels of West Eurasian admixture, as a result of the complex historical events occurred in the Peninsula. [ABSTRACT FROM AUTHOR]

European and African descendants settled the continental US during the 17th-19th centuries, coming into contact with established Native American populations. The resulting admixture among these groups yielded a significant reservoir of Native American ancestry in the modern US population. We analyzed the patterns of Native American admixture seen for the three largest genetic ancestry groups in the US population: African descendants, Western European descendants, and Spanish descendants. The three groups show distinct Native American ancestry profiles, which are indicative of their historical patterns of migration and settlement across the country. Native American ancestry in the modern African descendant population does not coincide with local geography, instead forming a single group with origins in the southeastern US, consistent with the Great Migration of the early 20th century. Western European descendants show Native American ancestry that tracks their geographic origins across the US, indicative of ongoing contact during westward expansion, and Native American ancestry can resolve Spanish descendant individuals into distinct local groups formed by more recent migration from Mexico and Puerto Rico. We found an anomalous pattern of Native American ancestry from the US southwest, which most likely corresponds to the Nuevomexicano descendants of early Spanish settlers to the region. We addressed a number of controversies surrounding this population, including the extent of Sephardic Jewish ancestry. Nuevomexicanos are less admixed than nearby Mexican-American individuals, with more European and less Native American and African ancestry, and while they do show demonstrable Sephardic Jewish ancestry, the fraction is no greater than seen for other New World Spanish descendant populations. [ABSTRACT FROM AUTHOR]

The origins of new genes are among the most fundamental questions in evolutionary biology. Our understanding of the ways that new genetic material appears and how that genetic material shapes population variation remains incomplete. De novo genes and duplicate genes are a key source of new genetic material on which selection acts. To better understand the origins of these new gene sequences, we explored the ways that structural variation might alter expression patterns and form novel transcripts. We provide evidence that chromosomal rearrangements are a source of novel genetic variation that facilitates the formation of de novo exons in Drosophila. We identify 51 cases of de novo exon formation created by chromosomal rearrangements in 14 strains of D. yakuba. These new genes inherit transcription start signals and open reading frames when the 5’ end of existing genes are combined with previously untranscribed regions. Such new genes would appear with novel peptide sequences, without the necessity for secondary transitions from non-coding RNA to protein. This mechanism of new peptide formations contrasts with canonical theory of de novo gene progression requiring non-coding intermediaries that must acquire new mutations prior to loss via pseudogenization. Hence, these mutations offer a means to de novo gene creation and protein sequence formation in a single mutational step, answering a long standing open question concerning new gene formation. We further identify gene expression changes to 134 existing genes, indicating that these mutations can alter gene regulation. Population variability for chromosomal rearrangements is considerable, with 2368 rearrangements observed across 14 inbred lines. More rearrangements were identified on the X chromosome than any of the autosomes, suggesting the X is more susceptible to chromosome alterations. Together, these results suggest that chromosomal rearrangements are a source of variation in populations that is likely to be important to explain genetic and therefore phenotypic diversity. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most common and essential serotype that causes salmonellosis in Guizhou province. This study aimed to investigate the antimicrobial resistance (AMR) and molecular genotyping of 79 S. Enteritidis clinical isolates from 2011 to 2016 in Guizhou, China. Antimicrobial resistance and minimum inhibitory concentrations (MICs) of S. Enteritidis clinical isolates were detected by micro broth dilution method against ten classes 16 antimicrobial agents, and molecular genotyping were examined by pulsed-field gel electrophoresis (PFGE) and multiple-locus variable-number tandem repeat analysis (MLVA). All (100%) isolates showed resistance to at least one antimicrobial. Resistance to nalidixic acid (98.7%) was the highest, followed by sulfamethoxazole (87.3%) and ampicillin (77.2%). The majority of isolates (92.4%) showed decreased susceptibility to ciprofloxacin. Resistance to the third and fourth-generation cephalosporins was observed. Twenty-six AMR profiles were observed, and the predominant AMR profile was ampicillin-streptomycin-sulfamethoxazole-amoxicillin/clavulanic acid-nalidixic acid. A high burden of multidrug resistance (MDR) (81.0%) was found. Seventy-nine S. Enteritidis isolates were divided into 33 different pulsotypes (PTs), and the most frequent PT was PT18. Twenty-six different MLVA types (MTs) were generated with seven VNTR loci analysis of these isolates. The dominant PTs and MTs were persistent during 2011–2016. S. Enteritidis clinical isolates showed higher genetic diversity using PFGE combined with MLVA grouped into 60 PT-MT genotypes. No correlation was observed between genotypes, AMR profiles and geographic location. These data revealed the characteristics of AMR and molecular genotyping of S. Enteritidis clinical isolates in Guizhou province. These results highlight that strengthening the AMR and molecular genotyping surveillance is essential to prevent and control salmonellosis in Guizhou. PFGE combined with MLVA should be powerful tools for the molecular genotyping of S. Enteritidis isolates. [ABSTRACT FROM AUTHOR]

The capacity of organisms to tune their development in response to environmental cues is pervasive in nature. This phenotypic plasticity is particularly striking in plants, enabled by their modular and continuous development. A good example is the activation of lateral shoot branches in Arabidopsis, which develop from axillary meristems at the base of leaves. The activity and elongation of lateral shoots depends on the integration of many signals both external (e.g. light, nutrient supply) and internal (e.g. the phytohormones auxin, strigolactone and cytokinin). Here, we characterise natural variation in plasticity of shoot branching in response to nitrate supply using two diverse panels of Arabidopsis lines. We find extensive variation in nitrate sensitivity across these lines, suggesting a genetic basis for variation in branching plasticity. High plasticity is associated with extreme branching phenotypes such that lines with the most branches on high nitrate have the fewest under nitrate deficient conditions. Conversely, low plasticity is associated with a constitutively moderate level of branching. Furthermore, variation in plasticity is associated with alternative life histories with the low plasticity lines flowering significantly earlier than high plasticity lines. In Arabidopsis, branching is highly correlated with fruit yield, and thus low plasticity lines produce more fruit than high plasticity lines under nitrate deficient conditions, whereas highly plastic lines produce more fruit under high nitrate conditions. Low and high plasticity, associated with early and late flowering respectively, can therefore be interpreted alternative escape vs mitigate strategies to low N environments. The genetic architecture of these traits appears to be highly complex, with only a small proportion of the estimated genetic variance detected in association mapping. [ABSTRACT FROM AUTHOR]

Sex-biased demographic events (“sex-bias”) involve unequal numbers of females and males. These events are typically inferred from the relative amount of X-chromosomal to autosomal genetic variation and have led to conflicting conclusions about human demographic history. Though population size changes alter the relative amount of X-chromosomal to autosomal genetic diversity even in the absence of sex-bias, this has generally not been accounted for in sex-bias estimators to date. Here, we present a novel method to identify sex-bias from genetic sequence data that models population size changes and estimates the female fraction of the effective population size during each time epoch. Compared to recent sex-bias inference methods, our approach can detect sex-bias that changes on a single population branch without requiring data from an outgroup or knowledge of divergence events. When applied to simulated data, conventional sex-bias estimators are biased by population size changes, especially recent growth or bottlenecks, while our estimator is unbiased. We next apply our method to high-coverage exome data from the 1000 Genomes Project and estimate a male bias in Yorubans (47% female) and Europeans (43%), possibly due to stronger background selection on the X chromosome than on the autosomes. Finally, we apply our method to the 1000 Genomes Project Phase 3 high-coverage Complete Genomics whole-genome data and estimate a female bias in Yorubans (63% female), Europeans (84%), Punjabis (82%), as well as Peruvians (56%), and a male bias in the Southern Han Chinese (45%). Our method additionally identifies a male-biased migration out of Africa based on data from Europeans (20% female). Our results demonstrate that modeling population size change is necessary to estimate sex-bias parameters accurately. Our approach gives insight into signatures of sex-bias in sexual species, and the demographic models it produces can serve as more accurate null models for tests of selection. [ABSTRACT FROM AUTHOR]

In studying the causative mechanisms behind migration and life history, the salmonids–salmon, trout, and charr–are an exemplary taxonomic group, as life history development is known to have a strong genetic component. A double inversion located on chromosome 5 in rainbow trout (Oncorhynchus mykiss) is associated with life history development in multiple populations, but the importance of this inversion has not been thoroughly tested in conjunction with other polymorphisms in the genome. To that end, we used a high-density SNP chip to genotype 192 F1 migratory and resident rainbow trout and focused our analyses to determine whether this inversion is important in life history development in a well-studied population of rainbow trout from Southeast Alaska. We identified 4,994 and 436 SNPs–predominantly outside of the inversion region–associated with life history development in the migrant and resident familial lines, respectively. Although F1 samples showed genomic patterns consistent with the double inversion on chromosome 5 (reduced observed and expected heterozygosity and an increase in linkage disequilibrium), we found no statistical association between the inversion and life history development. Progeny produced by crossing resident trout and progeny produced by crossing migrant trout both consisted of a mix of migrant and resident individuals, irrespective of the individuals’ inversion haplotype on chromosome 5. This suggests that although the inversion is present at a low frequency, it is not strongly associated with migration as it is in populations of Oncorhynchus mykiss from lower latitudes. [ABSTRACT FROM AUTHOR]

The diagnosis of Marfan spectrum includes a large number of clinical criteria. Although the identification of pathogenic variants contributes to the diagnostic process, its value to the prediction of clinical outcomes is still limited. An important novelty of the present study is represented by the statistical approach adopted to investigate genotype-phenotype correlation. The analysis has been improved considering the extended genetic information obtained by Next Generation Sequencing (NGS) and combining the effects of both rare and common genetic variants in an inclusive model. To this aim a cohort of 181 patients were analyzed with a NGS panel including 11 genes associated with Marfan spectrum. The genotype-phenotype correlation was also investigated considering the possibility to predict presence of a pathological mutation in Marfan syndrome (MFS) main genes based only on the analysis of phenotypic traits. Results obtained indicate that information about clinical traits can be summarized in a new variable that resulted significantly associated with the probability to find a pathological mutation in MFS main genes. This is important since the choice of the genetic test is often influenced by the phenotypic characterization of patients. Moreover, both rare and common variants were found to significantly contribute to clinical spectrum and their combination allowed to increase the percentage of phenotype variability that could be explained based on genetic factors. Results highlight the opportunity to take advantage of the overall genetic information obtained by NGS data to have a better clinical classification of patients. [ABSTRACT FROM AUTHOR]

Paterson’s curse (Echium plantagineum L. (Boraginaceae)), is an herbaceous annual native to Western Europe and northwest Africa. It has been recorded in Australia since the 1800’s and is now a major weed in pastures and rangelands, but its introduction history is poorly understood. An understanding of its invasion pathway and subsequent genetic structure is critical to the successful introduction of biological control agents and for provision of informed decisions for plant biosecurity efforts. We sampled E. plantagineum in its native (Iberian Peninsula), non-native (UK) and invaded ranges (Australia and South Africa) and analysed three chloroplast gene regions. Considerable genetic diversity was found among E. plantagineum in Australia, suggesting a complex introduction history. Fourteen haplotypes were identified globally, 10 of which were co-present in Australia and South Africa, indicating South Africa as an important source population, likely through contamination of traded goods or livestock. Haplotype 4 was most abundant in Australia (43%), and in historical and contemporary UK populations (80%), but scarce elsewhere (< 17%), suggesting that ornamental and/or other introductions from genetically impoverished UK sources were also important. Collectively, genetic evidence and historical records indicate E. plantagineum in southern Australia exists as an admixture that is likely derived from introduced source populations in both the UK and South Africa. [ABSTRACT FROM AUTHOR]

The Duffy blood group plays a key role in Plasmodium knowlesi and Plasmodium vivax invasion into human erythrocytes. The geographical distribution of the Duffy alleles differs between regions with the FY*A allele having high frequencies in many Asian populations, the FY*B allele is found predominately in European populations and the FY*Bes allele found predominantly in African regions. A previous study in Peninsular Malaysia indicated high homogeneity of the dominant FY*A/FY*A genotype. However, the distribution of the Duffy genotypes in Malaysian Borneo is currently unknown. In the present study, the distribution of Duffy blood group genotypes and allelic frequencies among P. knowlesi infected patients as well as healthy individuals in Malaysian Borneo were determined. A total of 79 P. knowlesi patient blood samples and 76 healthy donor samples were genotyped using allele specific polymerase chain reaction (ASP-PCR). Subsequently a P. knowlesi invasion assay was carried out on FY*AB/ FY*A and FY*A/ FY*A Duffy genotype blood to investigate if either genotype conferred increased susceptibility to P. knowlesi invasion. Our results show almost equal distribution between the homozygous FY*A/FY*A and heterozygous FY*A/FY*B genotypes. This is in stark contrast to the Duffy distribution in Peninsular Malaysia and the surrounding Southeast Asian region which is dominantly FY*A/FY*A. The mean percent invasion of FY*A/FY*A and FY*A/FY*B blood was not significantly different indicating that neither blood group confers increased susceptibility to P. knowlesi invasion. [ABSTRACT FROM AUTHOR]

To determine the origin and genetic consequences of anagenesis in Rubus takesimensis on Ulleung Island, Korea, we compared the genetic diversity and population structure of R. takesimensis with those of its continental progenitor R. crataegifolius. We broadly sampled a total of 315 accessions in 35 populations and sequenced five noncoding regions of chloroplast DNA. Rubus takesimensis emerged as nonmonophyletic and several geographically diverse continental populations were likely responsible for the origin of R. takesimensis; the majority of R. takesimensis accessions were sisters to the clade containing accessions of R. crataegifolius, primarily from the Korean peninsula, while rare accessions from three populations shared common ancestors with the ones from the southern part of the Korean peninsula, Jeju Island, and Japan. A few accessions from the Chusan population originated independently from the Korean peninsula. Of 129 haplotypes, 81 and 48 were found exclusively in R. crataegifolius and R. takesimensis, respectively. We found unusually high genetic diversity in two regions on Ulleung Island and no geographic population structure. For R. crataegifolius, two major haplotype groups were found; one for the northern mainland Korean peninsula, and the other for the southern Korean peninsula and the Japanese archipelago. Compared with populations of R. crataegifolius sampled from Japan, much higher haplotype diversity was found in populations from the Korean peninsula. The patterns of genetic consequences in R. takesimensis need to be verified for other endemic species based on chloroplast DNA and independent nuclear markers to synthesize emerging patterns of anagenetic speciation on Ulleung Island. [ABSTRACT FROM AUTHOR]

The Y chromosome harbors nine multi-copy ampliconic gene families expressed exclusively in testis. The gene copies within each family are >99% identical to each other, which poses a major challenge in evaluating their copy number. Recent studies demonstrated high variation in Y ampliconic gene copy number among humans. However, how this variation affects expression levels in human testis remains understudied. Here we developed a novel computational tool Ampliconic Copy Number Estimator (AmpliCoNE) that utilizes read sequencing depth information to estimate Y ampliconic gene copy number per family. We applied this tool to whole-genome sequencing data of 149 men with matched testis expression data whose samples are part of the Genotype-Tissue Expression (GTEx) project. We found that the Y ampliconic gene families with low copy number in humans were deleted or pseudogenized in non-human great apes, suggesting relaxation of functional constraints. Among the Y ampliconic gene families, higher copy number leads to higher expression. Within the Y ampliconic gene families, copy number does not influence gene expression, rather a high tolerance for variation in gene expression was observed in testis of presumably healthy men. No differences in gene expression levels were found among major Y haplogroups. Age positively correlated with expression levels of the HSFY and PRY gene families in the African subhaplogroup E1b, but not in the European subhaplogroups R1b and I1. We also found that expression of five out of six Y ampliconic gene families is coordinated with that of their non-Y (i.e. X or autosomal) homologs. Indeed, five ampliconic gene families had consistently lower expression levels when compared to their non-Y homologs suggesting dosage regulation, while the HSFY family had higher expression levels than its X homolog and thus lacked dosage regulation. [ABSTRACT FROM AUTHOR]

Introduction: In Tunisia, almost 77% of clinically and bacteriologically diagnosed cases of extrapulmonary tuberculosis (EPTB) are zoonotic TB, caused by M. bovis. Although several studies have analyzed bovine TB in cattle in Tunisia, no study has evaluated the risk of transmission to humans in such an endemic country. We aimed to study the genetic diversity of M. bovis human isolates, to ascertain the causes of human EPTB infection by M. bovis and to investigate the distribution and population structure of this species in Tunisia. Materials and methods: A total of 110 M. bovis isolates taken from patients with confirmed EPTB were characterized by spoligotyping and MIRU-VNTR typing methods. Results: Among the 15 spoligotypes detected in our study, 6 (SB0120, SB0121, SB2025, SB1200, SB1003 and SB0134) were the most prevalent (83.5%) of which SB0120, SB0121 and SB2025 were the most prevailing. MIRU-VNTR typing method showed a high genotypic and genetic diversity. The genetic differentiation based on MIRU-VNTR was significant between populations from South East (Tataouine, Medenine) and Central West (Gafsa, Sidi Bouzid, Kasserine) regions. Of note, 13/15 (86.7%) spoligotypes detected in our study were previously identified in cattle in Tunisia with different frequencies suggesting a peculiar ability of some genotypes to infect humans. Using combined spoligotyping and MIRU-VNTR method, a high clustering rate of 43.9% was obtained. Our results underlined that human EPTB due to M. bovis was more commonly found in female gender and in young patients. Most of our patients, 66.4% (73/110) were raw milk or derivatives consumers, whereas 30.9% (34/110) patients would have contracted EPTB through contact with livestock. The findings suggest that the transmission of Zoonotic TB caused by M. bovis to humans mainly occurred by oral route through raw milk or derivatives. Conclusion: Our study showed the urgent need of a better veterinary control with the implementation of effective and comprehensive strategies in order to reach a good protection of animals as well as human health. [ABSTRACT FROM AUTHOR]

In the Americas, as in much of the rest of the world, the dengue virus vector Aedes aegypti is found in close association with human habitations, often leading to high population densities of mosquitoes in urban settings. In the Peruvian Amazon, this vector has been expanding to rural communities over the last 10–15 years, but to date, the population genetic structure of Ae. aegypti in this region has not been characterized. To investigate the relationship between Ae. aegypti gene flow and human transportation networks, we characterized mosquito population structure using a panel of 8 microsatellite markers and linked results to various potential mechanisms for long-distance dispersal. Adult and immature Ae. aegypti (>20 individuals per site) were collected from Iquitos city and from six neighboring riverine communities, i.e., Nauta, Indiana, Mazan, Barrio Florida, Tamshiaco, and Aucayo. FST statistics indicate significant, but low to moderate differentiation for the majority of study site pairs. Population structure of Ae. aegypti is not correlated with the geographic distance between towns, suggesting that human transportation networks provide a reasonable explanation for the high levels of population mixing. Our results indicate that Ae. aegypti gene flow among sub-populations is greatest between locations with heavy boat traffic, such as Iquitos-Tamshiaco and Iquitos-Indiana-Mazan, and lowest between locations with little or no boat/road traffic between them such as Barrio Florida-Iquitos. Bayesian clustering analysis showed ancestral admixture among three genetic clusters; no single cluster was exclusive to any site. Our results are consistent with the hypothesis that human transportation networks, particularly riverways, are responsible for the geographic spread of Ae. aegypti in the Peruvian Amazon. Our findings are applicable to other regions of the world characterized by networks of urban islands connected by fluvial transport routes. [ABSTRACT FROM AUTHOR]

Genetic variation and population structure may reflect important information for invasion success of exotic plant species and thus help improve management of invasive plants. Spartina alterniflora is an invasive plant that is a major threat to the economy and environment of the coastal regions in China. We analyzed the genetic structure and diversity of six populations of S. alterniflora differing in invasion histories in Guangxi, China. A total of 176 individuals from the six populations produced 348 AFLP fragments. The average heterozygosity was significantly lower than in the native population. And genetic bottlenecks were also detected in most populations. Standardized FST statistics (Φpt = 0.015) and AMOVA results indicated weak genetic differentiation. Genetic admixture and obviously isolation by distance indicated populations in Guangxi come from a pre-admixed population by a single introduction. High phenotypic variations of S. alterniflora in Guangxi influenced by soil salinity and temperature might be an important reason for the successful invasion. [ABSTRACT FROM AUTHOR]

There are a few well-known indigenous breeds of Chinese rabbits in Sichuan and Fujian provinces, for which the genetic diversity and population structure have been poorly investigated. In the present study, we successfully employed the restriction-site-associated DNA sequencing (RAD-seq) approach to comprehensively discover genome-wide SNPs of 104 rabbits from four Chinese indigenous breeds: 30 Sichuan White, 34 Tianfu Black, 32 Fujian Yellow and eight Fujian Black. A total of 7,055,440 SNPs were initially obtained, from which 113,973 high-confidence SNPs (read depth ≥ 3, calling rate = 100% and biallelic SNPs) were selected to study the genetic diversity and population structure. The mean polymorphism information content (PIC) and nucleotide diversity (π) of each breed slightly varied with ranging from 0.2000 to 0.2281 and from 0.2678 to 0.2902, respectively. On the whole, Fujian Yellow rabbits showed the highest genetic diversity, which was followed by Tianfu Black and Sichuan White rabbits. The principal component analysis (PCA) revealed that the four breeds were clearly distinguishable. Our results first reveal the genetic differences among these four rabbit breeds in the Sichuan and Fujian provinces and also provide a high-confidence set of genome-wide SNPs for Chinese indigenous rabbits that could be employed for gene linkage and association analyses in the future. [ABSTRACT FROM AUTHOR]

Most current methods for detecting natural selection from DNA sequence data are limited in that they are either based on summary statistics or a composite likelihood, and as a consequence, do not make full use of the information available in DNA sequence data. We here present a new importance sampling approach for approximating the full likelihood function for the selection coefficient. Our method treats the ancestral recombination graph (ARG) as a latent variable that is integrated out using previously published Markov Chain Monte Carlo (MCMC) methods. The method can be used for detecting selection, estimating selection coefficients, testing models of changes in the strength of selection, estimating the time of the start of a selective sweep, and for inferring the allele frequency trajectory of a selected or neutral allele. We perform extensive simulations to evaluate the method and show that it uniformly improves power to detect selection compared to current popular methods such as nSL and SDS, and can provide reliable inferences of allele frequency trajectories under many conditions. We also explore the potential of our method to detect extremely recent changes in the strength of selection. We use the method to infer the past allele frequency trajectory for a lactase persistence SNP (MCM6) in Europeans. We also infer the trajectory of a SNP (EDAR) in Han Chinese, finding evidence that this allele’s age is much older than previously claimed. We also study a set of 11 pigmentation-associated variants. Several genes show evidence of strong selection particularly within the last 5,000 years, including ASIP, KITLG, and TYR. However, selection on OCA2/HERC2 seems to be much older and, in contrast to previous claims, we find no evidence of selection on TYRP1. [ABSTRACT FROM AUTHOR]

The South American plains vizcacha, Lagostomus maximus inhabits primarily the Pampean and adjoining Espinal, Monte and Chaquenean regions of Argentina. In order to study the population genetic structure of L. maximus, a fragment of 560 bp of the mitochondrial DNA hypervariable region 1from 90 individuals collected from the 3 subspecies and 8 groups along Argentina was amplified and analyzed. We found 9 haplotypes. The haplotype network did not show an apparent phylogeographical signal. Although low levels of genetic variation were found in all the subspecies and groups analyzed, a radiation of L. maximus would have occurred from the North and Center of the Pampean region toward the rest of its geographic range in Argentina. Low levels of genetic diversity, the existence of a single genetically distinct population in Argentina and changes of its effective size indicate that metapopulation processes and changes in human population dynamics during the late-Holocene were important factors shaping the population genetic structure of L. maximus in Argentina. [ABSTRACT FROM AUTHOR]

We investigated the phylogeography of the dugong (Dugong dugon) across its original range using museum material from 14 natural history museum and university collections. The mitochondrial DNA control region was successfully amplified from samples of bone or tooth powder from 162 individuals. These samples range from 1827 to 1996 and span the historical distribution range of the dugong. We were able to successfully amplify overlapping fragments of the D-loop region of the mitochondrial DNA (mtDNA) resulting in sequences of a 355 bp fragment for 162 individuals for the final analyses. This included a new sequence (189 bp) from a previously unidentified piece of skin of the extinct Steller’s sea cow (Hydrodamalis gigas), as an outgroup. The resulting dugong sequences match those from previous studies of dugongs from Australia and Indonesia, but revealed several new and divergent mtDNA lineages in the Indian Ocean. One mtDNA lineage includes most specimens from the Western Indian Ocean, with another distinct lineage isolated to nearby Madagascar and Comores. There is little geographic structuring detectable among other populations in the Western Indian Ocean and all populations from that region appear to have historically contained comparatively low levels of genetic diversity. The genetic diversity of several Indian Ocean samples collected after 1950 was lower than that of the samples collected earlier from similar locations, a result coincident with the anecdotal reductions in population size. The new lineages and potential loss of diversity highlight the particular conservation importance and vulnerability of dugong populations in the Western Indian Ocean. [ABSTRACT FROM AUTHOR]

A comprehensive, accurate, and revisable alpha taxonomy is crucial for biodiversity studies, but is challenging when data from reference specimens are difficult to collect or observe. However, recent technological advances can overcome some of these challenges. To illustrate this, we used modern approaches to tackle a centuries-old taxonomic enigma presented by Fraser’s Clawed Frog, Xenopus fraseri, including whether X. fraseri is different from other species, and if so, where it is situated geographically and phylogenetically. To facilitate these inferences, we used high-resolution techniques to examine morphological variation, and we generated and analyzed complete mitochondrial genome sequences from all Xenopus species, including >150-year-old type specimens. Our results demonstrate that X. fraseri is indeed distinct from other species, firmly place this species within a phylogenetic context, and identify its minimal geographic distribution in northern Ghana and northern Cameroon. These data also permit novel phylogenetic resolution into this intensively studied and biomedically important group. Xenopus fraseri was formerly thought to be a rainforest endemic placed alongside species in the amieti species group; in fact this species occurs in arid habitat on the borderlands of the Sahel, and is the smallest member of the muelleri species group. This study illustrates that the taxonomic enigma of Fraser’s frog was a combined consequence of sparse collection records, interspecies conservation and intraspecific polymorphism in external anatomy, and type specimens with unusual morphology. [ABSTRACT FROM AUTHOR]

The microbiome plays a key role in the biology, ecology and evolution of arthropod vectors of human pathogens. Vector-bacterial interactions could alter disease transmission dynamics through modulating pathogen replication and/or vector fitness. Nonetheless, our understanding of the factors shaping the bacterial community in arthropod vectors is incomplete. Using large-scale 16S amplicon sequencing, we examine how habitat disturbance structures the bacterial assemblages of field-collected whole-body hematophagous arthropods that vector human pathogens including mosquitoes (Culicidae), sand flies (Psychodidae), biting midges (Ceratopogonidae) and hard ticks (Ixodidae). We found that all comparisons of the bacterial community among species yielded statistically significant differences, but a difference was not observed between adults and nymphs of the hard tick, Haemaphysalis juxtakochi. While Culicoides species had the most distinct bacterial community among dipterans, tick species were composed of entirely different bacterial OTU’s. We observed differences in the proportions of some bacterial types between pristine and disturbed habitats for Coquillettidia mosquitoes, Culex mosquitoes, and Lutzomyia sand flies, but their associations differed within and among arthropod assemblages. In contrast, habitat quality was a poor predictor of differences in bacterial classes for Culicoides biting midges and hard tick species. In general, similarities in the bacterial communities among hematophagous arthropods could be explained by their phylogenetic relatedness, although intraspecific variation seems influenced by habitat disturbance. [ABSTRACT FROM AUTHOR]

Background: Pregnane X receptor (PXR) regulates the expression of drug-metabolizing enzymes and transport enzymes. NF-κB not only plays a role in liver homeostasis and injury-healing processes by regulating inflammatory responses but may also regulate the transcription of PXR. Currently, genetic polymorphisms in PXR are associated with adverse drug effects. Because little is known about the association between NF-κB1 genetic polymorphisms and adverse drug reactions, we explored the association between PXR and NF-κB1 single nucleotide polymorphisms (SNPs) and susceptibility to anti-tuberculosis drug-induced liver injury (ATDILI). Materials and methods: A total of 746 tuberculosis patients (118 with ATDILI and 628 without ATDILI) were prospectively enrolled at West China Hospital between December 2014 and April 2018. Nine selected SNPs (rs3814055, rs13059232, rs7643645 and rs3732360 in PXR and rs78872571, rs4647992, rs60371688, rs1598861 and rs3774959 in NF-κB1) were genotyped with a custom-designed 2x48-plex SNP Scan TM Kit. The frequencies of the alleles, genotypes and genetic models of the variants were compared between patients with or without ATDILI, while joint effect analysis of the SNP-SNP interactions was performed using multiplicative and additive models. The odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. Results: The T allele of rs3814055 in PXR was associated with a decreased risk for ATDILI (OR 0.61; 95% CI: 0.42–0.89, p = 0.0098). The T alleles of rs78872571 and rs4647992 in NF-κB1 were significantly associated with an increased risk for ATDILI (OR 1.91; 95% CI: 1.06–3.43, p = 0.028 and OR 1.81; 1.06–3.10, p = 0.029, respectively). The allele, genotype and genetic model frequencies were similar in the two groups for the other six SNPs (all P>0.05). There were no multiplicative or additive interactions between the SNPs. Conclusion: Our study is the first to reveal that rs3814055 variants in PXR and rs78872571 and rs4647992 variants in NF-κB1 are associated with susceptibility to ATDILI caused by first-line anti-tuberculosis combination treatment in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis (BTB) is endemic to the African buffalo (Syncerus caffer) of Hluhluwe-iMfolozi Park (HiP) and Kruger National Park, South Africa. In HiP, the disease has been actively managed since 1999 through a test-and-cull procedure targeting BTB-positive buffalo. Prior studies in Kruger showed associations between microsatellite alleles, BTB and body condition. A sex chromosomal meiotic drive, a form of natural gene drive, was hypothesized to be ultimately responsible. These associations indicate high-frequency occurrence of two types of male-deleterious alleles (or multiple-allele haplotypes). One type negatively affects body condition and BTB resistance in both sexes. The other type has sexually antagonistic effects: negative in males but positive in females. Here, we investigate whether a similar gene drive system is present in HiP buffalo, using 17 autosomal microsatellites and microsatellite-derived Y-chromosomal haplotypes from 401 individuals, culled in 2002–2004. We show that the association between autosomal microsatellite alleles and BTB susceptibility detected in Kruger, is also present in HiP. Further, Y-haplotype frequency dynamics indicated that a sex chromosomal meiotic drive also occurred in HiP. BTB was associated with negative selection of male-deleterious alleles in HiP, unlike positive selection in Kruger. Birth sex ratios were female-biased. We attribute negative selection and female-biased sex ratios in HiP to the absence of a Y-chromosomal sex-ratio distorter. This distorter has been hypothesized to contribute to positive selection of male-deleterious alleles and male-biased birth sex ratios in Kruger. As previously shown in Kruger, microsatellite alleles were only associated with male-deleterious effects in individuals born after wet pre-birth years; a phenomenon attributed to epigenetic modification. We identified two additional allele types: male-specific deleterious and beneficial alleles, with no discernible effect on females. Finally, we discuss how our findings may be used for breeding disease-free buffalo and implementing BTB test-and-cull programs. [ABSTRACT FROM AUTHOR]

The biological significance of regional cladoceran morphotypes in the montane regions of the central Palearctic remains poorly understood. In the Holarctic Daphnia longispina complex (Cladocera: Daphniidae), several variants, lineages and species have been proposed as endemic for Southern Siberia. Daphnia turbinata Sars, for example, named after its unusual head shape, is known only from Southern Siberia. Here we sequence DNA of Daphnia from three mitochondrial genes (12S rRNA, 16S rRNA, and NADH dehydrogenase subunit 2, ND2) from 57 localities in Russia and Mongolia (the majority being from Southern Siberia) and place them in evolutionary context with existing data. Our aim was to examine regional endemism of the Daphnia longispina complex in Southern Siberian; to improve the phylogenetic understanding with improved taxonomic and regional sampling, and to better understand the influence of Pleistocene glaciation on the biogeography of these lineages. At least three lineages showed genetic evidence for endemism in Southern Siberia. There was strong support for D. turbinata as a sister lineage to to D. longispina/D. dentifera. Another endemic, Siberian D. cf. longispina, is a sister group to the longispina group in general. Within D. longispina s. str. there was an endemic Siberian clade with a western range boundary near the Yenisei River Basin. Gene flow estimates among populations (based on FST values) were very low for clades of D. longispina on a regional (the original 12S dataset), and on a pan-Eurasian (the extended 12S dataset) scale. Negative values of Fu’s FS and Tajima’s D tests prevailed for the species examined with significant values found for two D. longispina clades, D. dentifera, D. galeata and D. cristata. Our results support the notion that Southern Siberia is an important biogeographic region for cladocerans as it contained unexpected diversity of endemics (such as D. turbinata, D. cf. longispina and lineages of D. umbra and D. longsipina s.str.) and from being the geographic meeting place of expanding postglacial lineages from eastern and western refugia. [ABSTRACT FROM AUTHOR]

The production of anticompetitor toxins is widespread among bacteria. Because production of such toxins is costly, it is typically regulated. In particular, many toxins are produced only when the local cell density is high. It is unclear which selection pressures shaped the evolution of density-dependent regulation of toxin production. Here, we study the evolution of toxin production, resistance and the response to a cell-density cue in a model of an evolving bacterial population with spatial structure. We present results for two growth regimes: (i) an undisturbed, fixed habitat in which only small fluctuations of cell density occur, and (ii) a serial-transfer regime with large fluctuations in cell density. We find that density-dependent toxin production can evolve under both regimes. However, the selection pressures driving the evolution of regulation differ. In the fixed habitat, regulation evolves because it allows cells to produce toxin only when opportunities for reproduction are highly limited (because of a high local cell density), and the effective fitness costs of toxin production are hence low. Under serial transfers, regulation evolves because it allows cells to switch from a fast-growing non-toxic phenotype when colonising a new habitat, to a slower-growing competitive toxic phenotype when the cell density increases. Colonies of such regulating cells rapidly expand into unoccupied space because their edges consist of fast-growing, non-toxin-producing cells, but are also combative because cells at the interfaces with competing colonies do produce toxin. Because under the two growth regimes different types of regulation evolve, our results underscore the importance of growth conditions in the evolution of social behaviour in bacteria. [ABSTRACT FROM AUTHOR]

The microbial communities that inhabit the distal gut of humans and other mammals exhibit large inter-individual variation. While host genetics is a known factor that influences gut microbiota composition, the mechanisms underlying this variation remain largely unknown. Bile acids (BAs) are hormones that are produced by the host and chemically modified by gut bacteria. BAs serve as environmental cues and nutrients to microbes, but they can also have antibacterial effects. We hypothesized that host genetic variation in BA metabolism and homeostasis influence gut microbiota composition. To address this, we used the Diversity Outbred (DO) stock, a population of genetically distinct mice derived from eight founder strains. We characterized the fecal microbiota composition and plasma and cecal BA profiles from 400 DO mice maintained on a high-fat high-sucrose diet for ~22 weeks. Using quantitative trait locus (QTL) analysis, we identified several genomic regions associated with variations in both bacterial and BA profiles. Notably, we found overlapping QTL for Turicibacter sp. and plasma cholic acid, which mapped to a locus containing the gene for the ileal bile acid transporter, Slc10a2. Mediation analysis and subsequent follow-up validation experiments suggest that differences in Slc10a2 gene expression associated with the different strains influences levels of both traits and revealed novel interactions between Turicibacter and BAs. This work illustrates how systems genetics can be utilized to generate testable hypotheses and provide insight into host-microbe interactions. [ABSTRACT FROM AUTHOR]

Leishmania (Leishmania) infantum is the zoonotic agent of visceral leishmaniasis (VL), a disease with a global distribution. The transmission scenario of VL has been undergoing changes worldwide, with the biologic cycle invading urbanized areas and dispersing the parasites into other previously free areas. The epidemiological cycle in Brazil has dispersed from the Northeast to other regions of the country. In this study, an integrative approach, including genotyping Brazilian strains of L. (L.) infantum for 14 microsatellite markers and reviewing historical records of the disease, was used to assess dispersion routes throughout central-southern Brazil. Our results support three L. (L.) infantum dispersion routes: A) dispersion from Bolivia to the states of Mato Grosso, Mato Grosso do Sul and São Paulo via the Bolivia-Brazil gas pipeline from 1998 to 2005; B) VL dispersion from Paraguay to the Brazilian side of the triple border (Foz do Iguaçu and Santa Terezinha de Itaipu) during after 2012; and C) emergence of a new L. (L.) infantum cluster in western Santa Catarina State and its dispersion to southern Paraná State (municipality of Pato Branco), after 2013. Hypotheses regarding possible entries of Leishmania (L.) infantum into the area of the triple border are presented and discussed. Understanding how VL has dispersed is vital to the development of control measures for this disease and to avoid future dispersion events. [ABSTRACT FROM AUTHOR]

The heterotrophic flagellate Percolomonas cosmopolitus (Heterolobosea) is often observed in saline habitats worldwide, from coastal waters to saturated brines. However, only two cultures assigned to this morphospecies have been examined using molecular methods, and their 18S rRNA gene sequences are extremely different. Further the salinity tolerances of individual strains are unknown. Thus, our knowledge on the autecology and diversity in this morphospecies is deficient. Here, we report 18S rRNA gene data on seven strains similar to P. cosmopolitus from seven geographically remote locations (New Zealand, Kenya, Korea, Poland, Russia, Spain, and the USA) with sample salinities ranging from 4‰ to 280‰, and compare morphology and salinity tolerance of the nine available strains. Percolomonas cosmopolitus-like strains show few-to-no consistent morphological differences, and form six clades separated by often extremely large 18S rRNA gene divergences (up to 42.4%). Some strains grow best at salinities from 75 to 125‰ and represent halophiles. All but one of these belong to two geographically heterogeneous clusters that form a robust monophyletic group in phylogenetic trees; this likely represents an ecologically specialized subclade of halophiles. Our results suggest that P. cosmopolitus is a cluster of several cryptic species (at least), which are unlikely to be distinguished by geography. Interestingly, the 9 Percolomonas strains formed a clade in 18S rRNA gene phylogenies, unlike most previous analyses based on two sequences. [ABSTRACT FROM AUTHOR]

In response to strong selection, new mutations can arise quickly and sweep through populations, particularly, if survival and reproduction depend on certain allele copies for adaptation to rapidly changing environments, like resistance against deadly diseases or strong toxins. Since the 1950s, resistance to anticoagulant rodenticides in several rodents has emerged through single nucleotide mutations in the vitamin-K-epoxid-reductase-complex-subunit-1 (VKORC1) gene, often located in its exon 3. Detection of high prevalence and concentrations of anticoagulant rodenticides in non-target vertebrates, including carnivorous Mustelidae, let us assume that secondary exposure by feeding on poisoned prey may also cause selection along the food chain and we hypothesized that VKORC1-based resistance might also have evolved in rodents’ predators. Using newly-developed mustelid-specific primers for direct sequencing of genomic DNA, we studied VKORC1-DNA-polymorphisms in 115 mustelids of five species (Martes martes, M. foina, Mustela nivalis, M. erminea, M. putorius), obtained from northern Denmark, yielding six sites with nonsynonymous and several synonymous amino acid polymorphisms in exon 3. Comparison of these VKORC1-genotypes with hepatic rodenticide residues (obtained by HPLC combined with fluorescence or mass spectrometry) in 83 individuals (except M. martes), using generalized linear models, suggested that anticoagulant levels depended on species and specific polymorphisms. Although most VKORC-1 polymorphisms may present standing genetic variation, some are situated in resistance-mediating membrane parts of the VKORC1-encoded protein, and might be a result of selection due to exposure to anticoagulant poisons. Our new molecular markers might allow detecting indirect effects of anticoagulant rodenticides on rodent predator populations in the future. [ABSTRACT FROM AUTHOR]

Cooperation among kin is common in animal societies. Kin groups may form by individuals directly discriminating relatives based on kin recognition cues, or form passively through natal philopatry and limited dispersal. We describe the genetic landscape for a primitively eusocial wasp, Polistes dominula, and ask whether individuals choose cooperative partners that are nearby and/or that are genetic relatives. Firstly, we genotyped an entire sub-population of 1361 wasps and found genetic structuring on an extremely fine scale: the probability of finding genetic relatives decreases exponentially within just a few meters of an individual’s nest. At the same time, however, we found a lack of genetic structuring between natural nest aggregations within the population. Secondly, in a separate dataset where ~2000 wasps were genotyped, we show that wasps forced experimentally to make a new nest choice tended to choose new nests near to their original nests, and that these nests tended to contain some full sisters. However, a significant fraction of wasps chose nests that did not contain sisters, despite sisters being present in nearby nests. Although we cannot rule out a role for direct kin recognition or natal nest-mate recognition, our data suggest that kin groups may form via a philopatric rule-of-thumb, whereby wasps simply select groups and nesting sites that are nearby. The result is that most subordinate helpers obtain indirect fitness benefits by breeding cooperatively. [ABSTRACT FROM AUTHOR]

Translocated saltwater crocodiles (Crocodylus porosus) in the Northern Territory (NT) of Australia often return to their original capture sites, which complicates management interventions aimed at reducing human-crocodile conflict. We examined the spatial events implicated in this homing ability, using ARGOS satellite tracking devices. Five large male C. porosus (3.03 m to 4.02 m TL) were shifted and released 100–320 km from their capture sites, and 3 additional ones (3.67 m to 4.23 m TL) were released at their site of capture as controls. Translocated crocodiles were more mobile than the controls, and moved at sea in the direction of their original capture site. However, they were unable or unwilling to swim around a geographic structure, Cobourg Peninsula, which prevented homing being achieved in all five cases. Two control crocodiles remained near their capture sites, but one, after the first year, made a 900km journey for six months, before returning to its original capture and release site. Genetic analysis of tissue samples from nests across the NT coast demonstrated significant genetic structure across the coast, and confirmed that Cobourg Peninsula contributes to genetic differentiation among populations along the NT coast. These results provide new insights into C. porosus movements, which have management significance for the maintenance of public safety. [ABSTRACT FROM AUTHOR]