Population stratification has long been recognized as a confounding factor in genetic association studies. Estimated ancestries, derived from multi-locus genotype data, can be used to perform a statistical correction for population stratification. One popular technique for estimation of ancestry is the model-based approach embodied by the widely applied program structure. Another approach, implemented in the program EIGENSTRAT, relies on Principal Component Analysis rather than model-based estimation and does not directly deliver admixture fractions. EIGENSTRAT has gained in popularity in part owing to its remarkable speed in comparison to structure. We present a new algorithm and a program, ADMIXTURE, for model-based estimation of ancestry in unrelated individuals. ADMIXTURE adopts the likelihood model embedded in structure. However, ADMIXTURE runs considerably faster, solving problems in minutes that take structure hours. In many of our experiments, we have found that ADMIXTURE is almost as fast as EIGENSTRAT. The runtime improvements of ADMIXTURE rely on a fast block relaxation scheme using sequential quadratic programming for block updates, coupled with a novel quasi-Newton acceleration of convergence. Our algorithm also runs faster and with greater accuracy than the implementation of an Expectation-Maximization (EM) algorithm incorporated in the program FRAPPE. Our simulations show that ADMIXTURE's maximum likelihood estimates of the underlying admixture coefficients and ancestral allele frequencies are as accurate as structure's Bayesian estimates. On real-world data sets, ADMIXTURE's estimates are directly comparable to those from structure and EIGENSTRAT. Taken together, our results show that ADMIXTURE's computational speed opens up the possibility of using a much larger set of markers in model-based ancestry estimation and that its estimates are suitable for use in correcting for population stratification in association studies.

The variant call format (VCF) is a generic format for storing DNA polymorphism data such as SNPs, insertions, deletions and structural variants, together with rich annotations. VCF is usually stored in a compressed manner and can be indexed for fast data retrieval of variants from a range of positions on the reference genome. The format was developed for the 1000 Genomes Project, and has also been adopted by other projects such as UK10K, dbSNP and the NHLBI Exome Project. VCFtools is a software suite that implements various utilities for processing VCF files, including validation, merging, comparing and also provides a general Perl API.http://vcftools.sourceforge.net

Advances in genome scanning using high-throughput sequencing technologies has led to a revolution in studies of non-model organisms. The glyptosternoid fish Creteuchiloglanis macropterus, is widely distributed in the main stem and tributaries of the Nujiang River basin. Here, we analyzed IIB restriction-site-associated DNA (2b-RAD) sequences and mitochondrial DNA sequences, to assess the genomic signature of adaptation by detecting and estimating the degree of genetic differentiation among ten Creteuchiloglanis macropterus populations from the Nujiang River. The analyses revealed significant population differentiation among the up-tributaries, main stem, mid-tributary and low-tributary. Annotation of contigs containing outlier SNPs revealed that the candidate genes showed significant enrichment in several important biological process terms between up-tributaries and low-tributary, and exhibited prominent enrichment in the term macromolecular metabolic process between all tributaries and the main stem. Population dynamics analyses indicated that the Late Pleistocene glaciations strongly influenced the demographic history of C. macropterus. Our results provide strong evidence for the utility of RAD-seq in population genetics studies, and our generated SNP resource should provide a valuable tool for population genomics studies of C. macropterus in the future.

Linear and heterogeneous habitat makes headwater stream networks an ideal ecosystem in which to test the influence of environmental factors on spatial genetic patterns of obligatory aquatic species. We investigated fine-scale population structure and influence of stream habitat on individual-level genetic differentiation in brook trout (Salvelinus fontinalis) by genotyping eight microsatellite loci in 740 individuals in two headwater channel networks (7.7 and 4.4 km) in Connecticut, USA. A weak but statistically significant isolation-by-distance pattern was common in both sites. In the field, many tagged individuals were recaptured in the same 50-m reaches within a single field season (summer to fall). One study site was characterized with a hierarchical population structure, where seasonal barriers (natural falls of 1.5-2.5 m in height during summer base-flow condition) greatly reduced gene flow and perceptible spatial patterns emerged because of the presence of tributaries, each with a group of genetically distinguishable individuals. Genetic differentiation increased when pairs of individuals were separated by high stream gradient (steep channel slope) or warm stream temperature in this site, although the evidence of their influence was equivocal. In a second site, evidence for genetic clusters was weak at best, but genetic differentiation between individuals was positively correlated with number of tributary confluences. We concluded that the population-level movement of brook trout was limited in the study headwater stream networks, resulting in the fine-scale population structure (genetic clusters and clines) even at distances of a few kilometres, and gene flow was mitigated by 'riverscape' variables, particularly by physical barriers, waterway distance (i.e. isolation-by-distance) and the presence of tributaries.© 2011 Blackwell Publishing Ltd.

As the rate of sequencing increases, greater throughput is demanded from read aligners. The full-text minute index is often used to make alignment very fast and memory-efficient, but the approach is ill-suited to finding longer, gapped alignments. Bowtie 2 combines the strengths of the full-text minute index with the flexibility and speed of hardware-accelerated dynamic programming algorithms to achieve a combination of high speed, sensitivity and accuracy.

White-spotted charr (Salvelinus leucomaenis leucomaenis) is an anadromous fish that has been severely harmed by human land-use development, particularly through habitat fragmentation. However, the anthropogenic impacts on populations of this species have not been evaluated, except those on small dammed-off populations. Using multiplexed ISSR genotyping by sequencing, we investigated the genetic structure of white-spotted charr in four tributaries in the upper section of the Kanayama Dam in the Sorachi River, Hokkaido Island, Japan. There were no distinct genetic structures (FST = 0.014), probably because some active individuals migrate frequently among tributaries. By model-flexible demographic simulation, historical changes in the effective population size were inferred. The result indicates that the population size has decreased since the end of the last glacial period, with three major population decline events, including recent declines that were probably associated with recent human activities. Nevertheless, populations in the watershed upstream of the Kanayama Dam are still expected to be at low risk of immediate extinction, owing to the large watershed size and the limited number of small check dams. An effective conservation measure for sustaining the white-spotted charr population is to maintain high connectivity between tributaries, such as by providing fishways in check dams during construction.

Population stratification--allele frequency differences between cases and controls due to systematic ancestry differences-can cause spurious associations in disease studies. We describe a method that enables explicit detection and correction of population stratification on a genome-wide scale. Our method uses principal components analysis to explicitly model ancestry differences between cases and controls. The resulting correction is specific to a candidate marker's variation in frequency across ancestral populations, minimizing spurious associations while maximizing power to detect true associations. Our simple, efficient approach can easily be applied to disease studies with hundreds of thousands of markers.

Phylogenies are increasingly used in all fields of medical and biological research. Moreover, because of the next-generation sequencing revolution, datasets used for conducting phylogenetic analyses grow at an unprecedented pace. RAxML (Randomized Axelerated Maximum Likelihood) is a popular program for phylogenetic analyses of large datasets under maximum likelihood. Since the last RAxML paper in 2006, it has been continuously maintained and extended to accommodate the increasingly growing input datasets and to serve the needs of the user community.I present some of the most notable new features and extensions of RAxML, such as a substantial extension of substitution models and supported data types, the introduction of SSE3, AVX and AVX2 vector intrinsics, techniques for reducing the memory requirements of the code and a plethora of operations for conducting post-analyses on sets of trees. In addition, an up-to-date 50-page user manual covering all new RAxML options is available.

Interpreting the genetic structure of a metapopulation as the outcome of gene flow over a variety of timescales is essential for the proper understanding of how changes in landscape affect biological connectivity. Here we contrast historical and contemporary connectivity in two metapopulations of the freshwater fish Galaxias platei in northern and southernmost Patagonia where paleolakes existed during the Holocene and Pleistocene, respectively. Contemporary gene flow was mostly high and asymmetrical in the northern system while extremely reduced in the southernmost system. Historical migration patterns were high and symmetric in the northern system and high and largely asymmetric in the southern system. Both systems showed a moderate structure with a clear pattern of isolation by distance (IBD). Effective population sizes were smaller in populations with low contemporary gene flow. An approximate Bayesian computation (ABC) approach suggests a late Holocene colonization of the lakes in the northern system and recent divergence of the populations from refugial populations from east and west of the Andes. For the southern system, the ABC approach reveals that some of the extant G. platei populations most likely derive from an ancestral population inhabiting a large Pleistocene paleolake while the rest derive from a higher-altitude lake. Our results suggest that neither historical nor contemporary processes individually fully explain the observed structure and geneflow patterns and both are necessary for a proper understanding of the factors that affect diversity and its distribution. Our study highlights the importance of a temporal perspective on connectivity to analyse the diversity of spatially complex metapopulations. © 2015 John Wiley & Sons Ltd.

Advances in next-generation sequencing techniques have allowed for the generation of genome-wide sequence data, to gain insight into the dynamics influencing genetic structure and the local adaptation of marine fish. Here, using genotyping-by-sequencing (GBS) technique, we identified 31,119 single nucleotide polymorphisms (SNPs) for Sebastiscus marmoratus in 59 individuals from three populations in Chinese coastal waters. Based on all SNPs, there was little evidence of genetic differentiation among populations. However, outlier tests revealed 329 SNPs putatively under divergent selection across populations. Structural and phylogenetic topology analyses based on the outliers showed clear genetic differentiation among populations. Gene Ontology (GO) annotation results revealed that most of these outliers are known or hypothesized to be involved in metabolic process. Together with previous work using mitochondrial cytochrome b sequences, the present results further suggest that the population structure is strongly influenced by locally adaptive pressure. Overall, adaptive evolution in a heterogeneous environment plays an important role in inducing genetic differentiation among local populations. This study increases understanding of the factors (including gene flow and local adaptation) promoting and constraining population genetic differentiation in marine organisms.