Spatial patterns of neutral genetic diversity are often investigated to infer gene flow in wild populations. However, teasing apart the influence of gene flow from the effect of genetic drift is challenging given that both forces are acting simultaneously on patterns of genetic differentiation. Here, we tested the relevance of a distance-based metric -based on estimates of effective population sizes or on environmental proxies for local carrying capacities- to assess the unique contribution of genetic drift on pairwise measures of genetic differentiation. Using simulations under various models of population genetics, we demonstrated that one of three metrics we tested was particularly promising: it correctly and uniquely captured variance in genetic differentiation that was due to genetic drift when this process was modelled. We further showed that (i) the unique contribution of genetic drift on genetic differentiation was high (up to 20 %) even when gene flow was high and for relatively high effective population sizes, and (ii) that this metric was robust to uncertainty in the estimation of local effective population size (or proxies for carrying capacity). Finally, using an empirical dataset on a freshwater fish (Gobio occitaniae), we demonstrated the usefulness of this metric to quantify the relative contribution of genetic drift and gene flow in explaining pattern of genetic differentiation in this species. We conclude that considering Isolation-by-Drift metrics will substantially improve the understanding of evolutionary drivers of observed spatial patterns of genetic variation.

In a fitness landscape, fitness values are associated to all genotypes corresponding to several, potentially all, combinations of a set of mutations. In the last decade, many small experimental fitness landscapes have been partially or completely resolved, and more will likely follow. MAGELLAN is a web-based graphical software to explore small fitness/energy landscapes through dynamic visualization and quantitative measures. It can be used to explore input custom landscapes, previously published experimental landscapes or randomly generated model landscapes.

Across western North America, Mimulus guttatus exists as many local populations adapted to site-specific challenges including salt spray, temperature, water availability, and soil chemistry. Gene flow between locally adapted populations will effect genetic diversity in both local demes and across the larger meta-population. A single population of annual M. guttatus from Iron Mountain, Oregon (IM) has been extensively studied and we here building off this research by analyzing whole genome sequences from 34 inbred lines from IM in conjunction with sequences from 22 Mimulus individuals from across the geographic range. Three striking features of these data address hypotheses about migration and selection in a locally adapted population. First, we find very high intra-population polymorphism (synonymous π = 0.033). Variation outside genes may be even higher, but is difficult to estimate because excessive divergence affects read mapping. Second, IM exhibits a significantly positive genome-wide average for Tajima’s D. This indicates allele frequencies are typically more intermediate than expected from neutrality, opposite the pattern observed in other species. Third, IM exhibits a distinctive haplotype structure. There is a genome-wide excess of positive associations between minor alleles; consistent with an important effect of gene flow from nearby Mimulus populations. The combination of multiple data types, including a novel, tree-based analytic method and estimates for structural polymorphism (inversions) from previous genetic mapping studies, illustrates how the balance of strong local selection, limited dispersal, and meta-population dynamics manifests across the genome.

The interaction between genetic drift and selection in shaping genetic diversity is not fully understood. In particular, a population’s propensity to drift is typically summarized by its long-term effective population size (N_e ), but rapidly changing population demographics may complicate this relationship. To better understand how changing demography impacts selection, we investigated linked selection in the genomes of 23 domesticated maize and 13 wild maize (teosinte) individuals. We show that maize went through a domestication bottleneck with a population size of approximately 5% that of teosinte before it experienced rapid expansion post-domestication. We observe that hard sweeps on genic mutations are not the primary force driving maize evolution. As expected, a reduced population size during domestication decreased the efficiency of purifying selection to purge deleterious alleles from maize, but rapid expansion after domestication has since increased the efficiency of purifying selection to levels exceeding those seen in teosinte. This final observation demonstrates that rapid demographic change can have wide-ranging impacts on diversity that conflict with would-be expectations based on long-term N_e.

Motivation: A series of methods in population genetics use multilocus genotype data to assign individuals membership in latent clusters. These methods belong to a broad class of mixed-membership models, such as latent Dirichlet allocation used to analyze text corpora. Inference from mixed-membership models can produce different output matrices when repeatedly applied to the same inputs, and the number of latent clusters is a parameter that is varied in the analysis pipeline. For these reasons, quantifying, visualizing, and annotating the output from mixed-membership models are bottlenecks for investigators. Results: Here, we introduce pong, a network-graphical approach for analyzing and visualizing membership in latent clusters with a D3.js interactive visualization. We apply this new method to 225,705 unlinked genome-wide single-nucleotide variants from 2,426 unrelated individuals in the 1000 Genomes Project, and show that pong outpaces current solutions by more than an order of magnitude in runtime while providing a customizable and interactive visualization of population structure that is more accurate than those produced by current tools. Availability: pong is freely available and can be installed using the Python package management system pip.

Complete gene knockouts are highly informative about gene function. We exome sequenced 3,222 British Pakistani-heritage adults with high parental relatedness, discovering 1,111 rare-variant homozygous likely loss of function (rhLOF) genotypes predicted to disrupt (knockout) 781 genes. Based on depletion of rhLOF genotypes, we estimate that 13.6% of knockouts are incompatible with adult life, finding on average 1.6 heterozygous recessive lethal LOF variants per adult. Linking to lifelong health records, we observed no association of rhLOF genotypes with prescription- or doctor-consultation rate, and no disease-related phenotypes in 33 of 42 individuals with rhLOF genotypes in recessive Mendelian disease genes. Phased genome sequencing of a healthy PRDM9 knockout mother, her child and controls, showed meiotic recombination sites localised away from PRDM9-dependent hotspots, demonstrating PRDM9 redundancy in humans.

In a classic example of the invasion of a species by a selfish genetic element, the P-element was horizontally transferred from a distantly related species into Drosophila melanogaster, where it caused a syndrome of abnormal phenotypes, including sterility, called “hybrid dysgenesis”. The P-element spread globally in the course of a few decades in D. melanogaster, while its sister species, including D. simulans, remained P-element free. Here, we find hybrid dysgenesis also occurs between D. simulans strains collected in different years; a survey of 154 strains shows that over one-third of them induce hybrid dysgenesis. Using genomic and transcriptomic data, we show that this dysgenesis-inducing phenotype is associated with the presence of the P-element, which has recently invaded D. simulans. We survey 573 D. simulans strains collected over the past 30 years for the presence of the P-element, and find that the D. simulans invasion of the P-element occurred rapidly, with infected strains across three continents being rare in 2004 and common by 2014. Importantly, strains collected from the latter phase of this invasion have adapted to ameliorate the effects of the P-element, as evidenced by their resistance to the hybrid dysgenesis phenotype. This work demonstrates that selfish elements can cause rapid global change in the genomes of their host species, even faster than previously thought.