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Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic data sets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and to the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed frameworkstdpopsimseeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version ofstdpopsimfocused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release ofstdpopsim(version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than three-fold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements tostdpopsimaim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone.

BACKGROUND & AIMS: The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced. We aimed to describe the health of adults with sucrase-isomaltase deficiency.METHODS: The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings.RESULTS: Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index (β [standard error], -2.0 [0.5] kg/m2; P = 3.1 × 10-5), body weight (-4.8 [1.4] kg; P = 5.1 × 10-4), fat percentage (-3.3% [1.0%]; P = 3.7 × 10-4), fasting triglyceride (-0.27 [0.07] mmol/L; P = 2.3 × 10-6), and remnant cholesterol (-0.11 [0.03] mmol/L; P = 4.2 × 10-5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (β [standard error], 0.056 [0.002] mmol/L; P = 2.1 × 10-26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test.CONCLUSIONS: These results suggest that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health, and that the health benefits are mediated by reduced dietary sucrose uptake and possibly also by higher levels of circulating acetate.

The common Arctic-specific

The common Arctic-specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this, we aimed to investigate the effect of p.G137S on metabolic health and cardiovascular disease risk among Greenlanders to quantify its impact on the population. In a population-based Greenlandic cohort (n = 5,063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. In addition, we explored the variant's impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n = 1,629); 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of serum LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischemic heart disease (HR [95% CI], 1.51 [1.18–1.92], p = 0.00096), peripheral artery disease (1.69 [1.01–2.82], p = 0.046), and coronary operations (1.78 [1.21–2.62], p = 0.0035). Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations.

In genomics-scale datasets, loci are closely packed within chromosomes and hence provide correlated information. Averaging across loci as if they were independent creates pseudoreplication, which reduces the effective degrees of freedom (df’) compared to the nominal degrees of freedom, df. This issue has been known for some time, but consequences have not been systematically quantified across the entire genome. Here we measured pseudoreplication (quantified by the ratio df’/df) for a common metric of genetic differentiation (FST) and a common measure of linkage disequilibrium between pairs of loci (r2). Based on data simulated using models (SLiM and msprime) that allow efficient forward-in-time and coalescent simulations while precisely controlling population pedigrees, we estimated df’ and df’/df by measuring the rate of decline in the variance of mean FST and mean r2 as more loci were used. For both indices, df’ increases with Ne and genome size, as expected. However, even for large Ne and large genomes, df’ for mean r2 plateaus after a few thousand loci, and a variance components analysis indicates that the limiting factor is uncertainty associated with sampling individuals rather than genes. Pseudoreplication is less extreme for FST, but df’/df ≤0.01 can occur in datasets using tens of thousands of loci. Commonly-used block-jackknife methods consistently overestimated var(FST), producing very conservative confidence intervals. Predicting df’ based on our modeling results as a function of Ne, L, S, and genome size provides a robust way to quantify precision associated with genomics-scale datasets.

Knowledge of how individuals are related is important in many areas of research, and numerous methods for inferring pairwise relatedness from genetic data have been developed. However, the majority of these methods were not developed for situations where data are limited. Specifically, most methods rely on the availability of population allele frequencies, the relative genomic position of variants and accurate genotype data. But in studies of non‐model organisms or ancient samples, such data are not always available. Motivated by this, we present a new method for pairwise relatedness inference, which requires neither allele frequency information nor information on genomic position. Furthermore, it can be applied not only to accurate genotype data but also to low‐depth sequencing data from which genotypes cannot be accurately called. We evaluate it using data from a range of human populations and show that it can be used to infer close familial relationships with a similar accuracy as a widely used method that relies on population allele frequencies. Additionally, we show that our method is robust to SNP ascertainment and applicable to low‐depth sequencing data generated using different strategies, including resequencing and RADseq, which is important for application to a diverse range of populations and species.

Large carnivores are generally sensitive to ecosystem changes because their specialized diet and position at the top of the trophic pyramid is associated with small population sizes. Accordingly, low genetic diversity at the whole-genome level has been reported for all big cat species, including the widely distributed leopard. However, all previous whole-genome analyses of leopards are based on the Far Eastern Amur leopards that live at the extremity of the species' distribution and therefore are not necessarily representative of the whole species. We sequenced 53 whole genomes of African leopards. Strikingly, we found that the genomic diversity in the African leopard is 2- to 5-fold higher than in other big cats, including the Amur leopard, likely because of an exceptionally high effective population size maintained by the African leopard throughout the Pleistocene. Furthermore, we detected ongoing gene flow and very low population differentiation within African leopards compared with those of other big cats. We corroborated this by showing a complete absence of an otherwise ubiquitous equatorial forest barrier to gene flow. This sets the leopard apart from most other widely distributed large African mammals, including lions. These results revise our understanding of trophic sensitivity and highlight the remarkable resilience of the African leopard, likely because of its extraordinary habitat versatility and broad dietary niche.

SUMMARY The Inuit ancestors of the Greenlandic people arrived in Greenland close to 1,000 years ago.1 Since then, Europeans from many different countries have been present in Greenland. Consequently, the present-day Greenlandic population has ~25% of its genetic ancestry from Europe.2 In this study, we investigated to what extent different European countries have contributed to this genetic ancestry. We combined dense SNP chip data from 3,972 Greenlanders and 8,275 Europeans from 14 countries and inferred the ancestry contribution from each of these 14 countries using haplotype-based methods. Due to the rapid increase in population size in Greenland over the past ~100 years, we hypothesized that earlier European interactions, such as pre-colonial Dutch whalers and early German and Danish-Norwegian missionaries, as well as the later Danish colonists and post-colonial immigrants, all contributed European genetic ancestry. However, we found that the European ancestry is almost entirely Danish and that a substantial fraction is from admixture that took place within the last few generations., In brief The Greenlandic Inuit have had extensive historical contact with Europeans, and the present-day Greenlandic population has substantial amounts of European ancestry. Waples et al. use genetic data to investigate the origin of this ancestry. They show that much of it is Danish and find little evidence of it being from pre-colonial European contact.

Whole genome duplications have occurred in the recent ancestors of many plants, fish, and amphibians, resulting in a pervasiveness of paralogous loci and the potential for both disomic and tetrasomic inheritance in the same genome. Paralogs can be difficult to reliably genotype and are often excluded from genotyping-by-sequencing (GBS) analyses; however, removal requires paralogs to be identified which is difficult without a reference genome. We present a method for identifying paralogs in natural populations by combining two properties of duplicated loci: 1) the expected frequency of heterozygotes exceeds that for singleton loci, and 2) within heterozygotes, observed read ratios for each allele in GBS data will deviate from the 1:1 expected for singleton (diploid) loci. These deviations are often not apparent within individuals, particularly when sequence coverage is low; but, we postulated that summing allele reads for each locus over all heterozygous individuals in a population would provide sufficient power to detect deviations at those loci. We identified paralogous loci in three species: Chinook salmon (Oncorhynchus tshawytscha) which retains regions with ongoing residual tetrasomy on eight chromosome arms following a recent whole genome duplication, mountain barberry (Berberis alpina) which has a large proportion of paralogs that arose through an unknown mechanism, and dusky parrotfish (Scarus niger) which has largely re-diploidized following an ancient whole genome duplication. Importantly, this approach only requires the genotype and allele-specific read counts for each individual, information which is readily obtained from most GBS analysis pipelines. This article is protected by copyright. All rights reserved.

Effective population size (Ne) is among the most important metrics in evolutionary biology. In natural populations, it is often difficult to collect adequate demographic data to calculate Ne directly. Consequently, genetic methods to estimate Ne have been developed. Two Ne estimators based on sibship reconstruction using multi-locus genotype data have been developed in recent years; sibship assignment and parentage analysis without parents. In this study, we evaluated the accuracy of sibship reconstruction using a large empirical dataset from five hatchery steelhead populations with known pedigrees and using 95 single nucleotide polymorphism (SNP) markers. We challenged the software COLONY with 2,599,961 known relationships and demonstrated that reconstruction of full-sib and unrelated pairs were greater than 95% and 99% accurate, respectively. However, reconstruction of half-sib pairs was poor (< 5% accurate). Despite poor half-sib reconstruction, both estimators provided accurate estimates of the effective number of breeders (Nb) when sample sizes were near or greater than the true Nb and when assuming a monogamous mating system. We further demonstrated that both methods provide roughly equivalent estimates of Nb. Our results indicate that sibship reconstruction and current SNP panels provide promise for estimating Nb in steelhead populations in the region. This article is protected by copyright. All rights reserved.

Contemporary effective population size (Ne) can be estimated using linkage disequilibrium (LD) observed across pairs of loci presumed to be selectively neutral and unlinked. This method has been commonly applied to data sets containing 10-100 loci to inform conservation and study population demography. Performance of these Ne estimates could be improved by incorporating data from thousands of loci. However, these thousands of loci exist on a limited number of chromosomes, ensuring that some fraction will be physically linked. Linked loci have elevated LD due to limited recombination, which if not accounted for can cause Ne estimates to be downwardly biased. Here, we present results from coalescent and forward simulations designed to evaluate the bias of LD-based Ne estimates ([Ncirc ]e). Contrary to common perceptions, increasing the number of loci does not increase the magnitude of linkage. Although we show it is possible to identify some pairs of loci that produce unusually large r(2) values, simply removing large r(2) values is not a reliable way to eliminate bias. Fortunately, the magnitude of bias in [Ncirc ]e is strongly and negatively correlated with the process of recombination, including the number of chromosomes and their length, and this relationship provides a general way to adjust for bias. Additionally, we show that with thousands of loci, precision of [Ncirc ]e is much lower than expected based on the assumption that each pair of loci provides completely independent information.

The role of rare variants in complex traits remains uncharted. Here, we conduct deep whole genome sequencing of 1457 individuals from an isolated population, and test for rare variant burdens across six cardiometabolic traits. We identify a role for rare regulatory variation, which has hitherto been missed. We find evidence of rare variant burdens that are independent of established common variant signals (ADIPOQ and adiponectin, P = 4.2 × 10−8; APOC3 and triglyceride levels, P = 1.5 × 10−26), and identify replicating evidence for a burden associated with triglyceride levels in FAM189B (P = 2.2 × 10−8), indicating a role for this gene in lipid metabolism., Rare genetic variants can contribute to complex traits but this contribution is not well understood. Here, the authors analyse deep whole genome sequencing data across 1457 individuals from an isolated Greek population and find association of rare variant burdens with cardiometabolic traits.

Coral reefs within the Coral Triangle (CT) are home to the greatest marine diversity on the globe and are an important supplier of marine resources to densely populated coastal regions. Many coral reefs within the CT and around the world are under threat from over-exploitation. Marine protected areas (MPAs) have been proven to be effective tools in restoring fish stocks. However, the role that MPAs play in promoting connectivity at greater distances through larval dispersal is still unknown. RADseq was used to discover 4253 SNPs from 81 individuals of the dusky parrotfish (Scarus niger) collected from three sites within the Philippines. A lack of population structure suggested a high rate of gene flow (F ST = 0.007). Estimates of Ne from linkage disequilibrium are relatively large, ranging from 1200 to 2000. A sibling analysis revealed one pair of well-supported full siblings (r = 0.773) and one pair of putative half siblings (r = 0.191) between sites separated by more than 500 km. The low F ST values indicate a high degree of gene flow between the reefs within the sampling area while the sibling analysis suggests demographic connectivity between the Sibuyan Sea and the Sulu Sea. The Mindoro–Panay throughflow is a likely vector by which larvae are transported between these sites, suggesting that reefs in Romblon are sources for reefs near Basay, 400 km to the south. Given the reliance of a vast majority of coral reef fishes on larval dispersal, this study reveals that MPAs established within the central Philippines can supply varying levels of larvae to overfished reefs.

Meiotic recombination is fundamental for generating new genetic variation and for securing proper disjunction. Further, recombination plays an essential role during the rediploidization process of polyploid-origin genomes because crossovers between pairs of homeologous chromosomes retain duplicated regions. A better understanding of how recombination affects genome evolution is crucial for interpreting genomic data; unfortunately, current knowledge mainly originates from a few model species. Salmonid fishes provide a valuable system for studying the effects of recombination in nonmodel species. Salmonid females generally produce thousands of embryos, providing large families for conducting inheritance studies. Further, salmonid genomes are currently rediploidizing after a whole genome duplication and can serve as models for studying the role of homeologous crossovers on genome evolution. Here, we present a detailed interrogation of recombination patterns in sockeye salmon (Oncorhynchus nerka). First, we use RAD sequencing of haploid and diploid gynogenetic families to construct a dense linkage map that includes paralogous loci and location of centromeres. We find a nonrandom distribution of paralogs that mainly cluster in extended regions distally located on 11 different chromosomes, consistent with ongoing homeologous recombination in these regions. We also estimate the strength of interference across each chromosome; results reveal strong interference and crossovers are mostly limited to one per arm. Interference was further shown to continue across centromeres, but metacentric chromosomes generally had at least one crossover on each arm. We discuss the relevance of these findings for both mapping and population genomic studies.

Whole-genome duplications have occurred in the recent ancestors of many plants, fish and amphibians. Signals of these whole-genome duplications still exist in the form of paralogous loci. Recent advances have allowed reliable identification of paralogs in genotyping-by-sequencing (GBS) data such as that generated from restriction-site-associated DNA sequencing (RADSeq); however, excluding paralogs from analyses is still routine due to difficulties in genotyping. This exclusion of paralogs may filter a large fraction of loci, including loci that may be adaptively important or informative for population genetic analyses. We present a maximum-likelihood method for inferring allele dosage in paralogs and assess its accuracy using simulated GBS, empirical RADSeq and amplicon sequencing data from Chinook salmon. We accurately infer allele dosage for some paralogs from a RADSeq data set and show how accuracy is dependent upon both read depth and allele frequency. The amplicon sequencing data set, using RADSeq-derived markers, achieved sufficient depth to infer allele dosage for all paralogs. This study demonstrates that RADSeq locus discovery combined with amplicon sequencing of targeted loci is an effective method for incorporating paralogs into population genetic analyses.

Whole-genome duplications are major evolutionary events with a lasting impact on genome structure. Duplication events complicate genetic analyses as paralogous sequences are difficult to distinguish; consequently, paralogs are often excluded from studies. The effects of an ancient whole-genome duplication (approximately 88 MYA) are still evident in salmonids through the persistence of numerous paralogous gene sequences and partial tetrasomic inheritance. We use restriction site-associated DNA sequencing on 10 collections of chum salmon from the Salish Sea in the USA and Canada to investigate genetic diversity and population structure in both tetrasomic and rediploidized regions of the genome. We use a pedigree and high-density linkage map to identify paralogous loci and to investigate genetic variation across the genome. By applying multivariate statistical methods, we show that it is possible to characterize paralogous loci and that they display similar patterns of population structure as the diploidized portion of the genome. We find genetic associations with the adaptively important trait of run-timing in both sets of loci. By including paralogous loci in genome scans, we can observe evolutionary signals in genomic regions that have routinely been excluded from population genetic studies in other polyploid-derived species.

Salmonids are an important cultural and ecological resource exhibiting near worldwide distribution between their native and introduced range. Previous research has generated linkage maps and genomic resources for several species as well as genome assemblies for two species. We first leveraged improvements in mapping and genotyping methods to create a dense linkage map for Chinook salmon Oncorhynchus tshawytscha by assembling family data from different sources. We successfully mapped 14 620 SNP loci including 2336 paralogs in subtelomeric regions. This improved map was then used as a foundation to integrate genomic resources for gene annotation and population genomic analyses. We anchored a total of 286 scaffolds from the Atlantic salmon genome to the linkage map to provide a framework for the placement 11 728 Chinook salmon ESTs. Previously identified thermotolerance QTL were found to colocalize with several candidate genes including HSP70, a gene known to be involved in thermal response, as well as its inhibitor. Multiple regions of the genome with elevated divergence between populations were also identified, and annotation of ESTs in these regions identified candidate genes for fitness related traits such as stress response, growth and behaviour. Collectively, these results demonstrate the utility of combining genomic resources with linkage maps to enhance evolutionary inferences.

The future spread and impact of an introduced species will depend on how it adapts to the abiotic and biotic conditions encountered in its new range, so the potential for rapid evolution subsequent to species introduction is a critical, evolutionary dimension of invasion biology. Using a resurrection approach, we provide a direct test for change over time within populations in a species' introduced range, in the Asian shade annual Polygonum cespitosum. We document, over an 11-year period, the evolution of increased reproductive output as well as greater physiological and root-allocational plasticity in response to the more open, sunny conditions found in the North American range in which the species has become invasive. These findings show that extremely rapid adaptive modifications to ecologically-important traits and plastic expression patterns can evolve subsequent to a species' introduction, within populations established in its introduced range. This study is one of the first to directly document evolutionary change in adaptive plasticity. Such rapid evolutionary changes can facilitate the spread of introduced species into novel habitats and hence contribute to their invasive success in a new range. The data also reveal how evolutionary trajectories can differ among populations in ways that can influence invasion dynamics.

An important use of genetic parentage analysis is the ability to directly calculate the number of offspring produced by each parent (ki) and hence effective population size, Ne. But what if parental genotypes are not available? In theory, given enough markers, it should be possible to reconstruct parental genotypes based entirely on a sample of progeny, and if so the vector of parental ki values. However, this would provide information only about parents that actually contributed offspring to the sample. How would ignoring the ‘null’ parents (those that produced no offspring) affect an estimate of Ne? The surprising answer is that null parents have no effect at all. We show that: (i) The standard formula for inbreeding Ne can be rewritten so that it is a function only of sample size and P k 2 �� ; it is not necessary to know the total number of parents (N). This same relationship does not hold for variance Ne. (ii) This novel formula provides an unbiased estimate of Ne even if only a subset of progeny is available, provided the parental contributions are accurately determined, in which case precision is also high compared to other single-sample estimators of Ne. (iii) It is not necessary to actually reconstruct parental genotypes; from a matrix of pairwise relationships (as can be estimated by some current software programs), it is possible to construct the vector of ki values and estimate Ne. The new method based on parentage analysis without parents (PwoP) can potentially be useful as a single-sample estimator of contemporary Ne, provided that either (i) relationships can be accurately determined, or (ii) P k 2 �� can be estimated directly.

The original version of this Article contained an error in Fig. 2. In panel a, the two legend items “rare” and “common” were inadvertently swapped. This has been corrected in both the PDF and HTML versions of the Article.

Studying the effect of similar environments on diverse genetic backgrounds has long been a goal of evolutionary biologists with studies typically relying on experimental approaches. Pink salmon, a highly abundant and widely ranging salmonid, provide a naturally occurring opportunity to study the effects of similar environments on divergent genetic backgrounds due to a strict two-year semelparous life history. The species is composed of two reproductively isolated lineages with overlapping ranges that share the same spawning and rearing environments in alternate years. We used restriction-site-associated DNA (RAD) sequencing to discover and genotype approximately 8000 SNP loci in three population pairs of even- and odd-year pink salmon along a latitudinal gradient in North America. We found greater differentiation within the odd-year than within the even-year lineage and greater differentiation in the southern pair from Puget Sound than in the northern Alaskan population pairs. We identified 15 SNPs reflecting signatures of parallel selection using both a differentiation-based method (BAYESCAN) and an environmental correlation method (BAYENV). These SNPs represent genomic regions that may be particularly informative in understanding adaptive evolution in pink salmon and exploring how differing genetic backgrounds within a species respond to selection from the same natural environment.

Recent advances in population genomics have made it possible to detect previously unidentified structure, obtain more accurate estimates of demographic parameters, and explore adaptive divergence, potentially revolutionizing the way genetic data are used to manage wild populations. Here, we identified 10 944 single-nucleotide polymorphisms using restriction-site-associated DNA (RAD) sequencing to explore population structure, demography, and adaptive divergence in five populations of Chinook salmon (Oncorhynchus tshawytscha) from western Alaska. Patterns of population structure were similar to those of past studies, but our ability to assign individuals back to their region of origin was greatly improved (>90% accuracy for all populations). We also calculated effective size with and without removing physically linked loci identified from a linkage map, a novel method for nonmodel organisms. Estimates of effective size were generally above 1000 and were biased downward when physically linked loci were not removed. Outlier tests based on genetic differentiation identified 733 loci and three genomic regions under putative selection. These markers and genomic regions are excellent candidates for future research and can be used to create high-resolution panels for genetic monitoring and population assignment. This work demonstrates the utility of genomic data to inform conservation in highly exploited species with shallow population structure.