scholarly journals Effects of linked selective sweeps on demographic inference and model selection

2016 ◽  
Author(s):  
Daniel R. Schrider ◽  
Alexander G. Shanku ◽  
Andrew D. Kern

AbstractThe availability of large-scale population genomic sequence data has resulted in an explosion in efforts to infer the demographic histories of natural populations across a broad range of organisms. As demographic events alter coalescent genealogies they leave detectable signatures in patterns of genetic variation within and between populations. Accordingly, a variety of approaches have been designed to leverage population genetic data to uncover the footprints of demographic change in the genome. The vast majority of these methods make the simplifying assumption that the measures of genetic variation used as their input are unaffected by natural selection. However, natural selection can dramatically skew patterns of variation not only at selected sites, but at linked, neutral loci as well. Here we assess the impact of recent positive selection on demographic inference by characterizing the performance of three popular methods through extensive simulation of datasets with varying numbers of linked selective sweeps. In particular, we examined three different demographic models relevant to a number of species, finding that positive selection can bias parameter estimates of each of these models—often severely. Moreover, we find that selection can lead to incorrect inferences of population size changes when none have occurred. We argue that the amount of recent positive selection required to skew inferences may often be acting in natural populations. These results suggest that demographic studies conducted in many species to date may have exaggerated the extent and frequency of population size changes.


2019 ◽  
Vol 36 (10) ◽  
pp. 2358-2374
Author(s):  
Nicolas Alcala ◽  
Amy Goldberg ◽  
Uma Ramakrishnan ◽  
Noah A Rosenberg

Abstract Natural populations display a variety of spatial arrangements, each potentially with a distinctive impact on genetic diversity and genetic differentiation among subpopulations. Although the spatial arrangement of populations can lead to intricate migration networks, theoretical developments have focused mainly on a small subset of such networks, emphasizing the island-migration and stepping-stone models. In this study, we investigate all small network motifs: the set of all possible migration networks among populations subdivided into at most four subpopulations. For each motif, we use coalescent theory to derive expectations for three quantities that describe genetic variation: nucleotide diversity, FST, and half-time to equilibrium diversity. We describe the impact of network properties on these quantities, finding that motifs with a high mean node degree have the largest nucleotide diversity and the longest time to equilibrium, whereas motifs with low density have the largest FST. In addition, we show that the motifs whose pattern of variation is most strongly influenced by loss of a connection or a subpopulation are those that can be split easily into disconnected components. We illustrate our results using two example data sets—sky island birds of genus Sholicola and Indian tigers—identifying disturbance scenarios that produce the greatest reduction in genetic diversity; for tigers, we also compare the benefits of two assisted gene flow scenarios. Our results have consequences for understanding the effect of geography on genetic diversity, and they can assist in designing strategies to alter population migration networks toward maximizing genetic variation in the context of conservation of endangered species.



Agronomy ◽  
2018 ◽  
Vol 8 (7) ◽  
pp. 119 ◽  
Author(s):  
Petr Smýkal ◽  
Matthew Nelson ◽  
Jens Berger ◽  
Eric Von Wettberg

Humans have domesticated hundreds of plant and animal species as sources of food, fiber, forage, and tools over the past 12,000 years, with manifold effects on both human society and the genetic structure of the domesticated species. The outcomes of crop domestication were shaped by selection driven by human preferences, cultivation practices, and agricultural environments, as well as other population genetic processes flowing from the ensuing reduction in effective population size. It is obvious that any selection imposes a reduction of diversity, favoring preferred genotypes, such as nonshattering seeds or increased palatability. Furthermore, agricultural practices greatly reduced effective population sizes of crops, allowing genetic drift to alter genotype frequencies. Current advances in molecular technologies, particularly of genome sequencing, provide evidence of human selection acting on numerous loci during and after crop domestication. Population-level molecular analyses also enable us to clarify the demographic histories of the domestication process itself, which, together with expanded archaeological studies, can illuminate the origins of crops. Domesticated plant species are found in 160 taxonomic families. Approximately 2500 species have undergone some degree of domestication, and 250 species are considered to be fully domesticated. The evolutionary trajectory from wild to crop species is a complex process. Archaeological records suggest that there was a period of predomestication cultivation while humans first began the deliberate planting of wild stands that had favorable traits. Later, crops likely diversified as they were grown in new areas, sometimes beyond the climatic niche of their wild relatives. However, the speed and level of human intentionality during domestication remains a topic of active discussion. These processes led to the so-called domestication syndrome, that is, a group of traits that can arise through human preferences for ease of harvest and growth advantages under human propagation. These traits included reduced dispersal ability of seeds and fruits, changes to plant structure, and changes to plant defensive characteristics and palatability. Domestication implies the action of selective sweeps on standing genetic variation, as well as new genetic variation introduced via mutation or introgression. Furthermore, genetic bottlenecks during domestication or during founding events as crops moved away from their centers of origin may have further altered gene pools. To date, a few hundred genes and loci have been identified by classical genetic and association mapping as targets of domestication and postdomestication divergence. However, only a few of these have been characterized, and for even fewer is the role of the wild-type allele in natural populations understood. After domestication, only favorable haplotypes are retained around selected genes, which creates a genetic valley with extremely low genetic diversity. These “selective sweeps” can allow mildly deleterious alleles to come to fixation and may create a genetic load in the cultivated gene pool. Although the population-wide genomic consequences of domestication offer several predictions for levels of the genetic diversity in crops, our understanding of how this diversity corresponds to nutritional aspects of crops is not well understood. Many studies have found that modern cultivars have lower levels of key micronutrients and vitamins. We suspect that selection for palatability and increased yield at domestication and during postdomestication divergence exacerbated the low nutrient levels of many crops, although relatively little work has examined this question. Lack of diversity in modern germplasm may further limit our capacity to breed for higher nutrient levels, although little effort has gone into this beyond a handful of staple crops. This is an area where an understanding of domestication across many crop taxa may provide the necessary insight for breeding more nutritious crops in a rapidly changing world.



eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Wen Huang ◽  
Richard F Lyman ◽  
Rachel A Lyman ◽  
Mary Anna Carbone ◽  
Susan T Harbison ◽  
...  

Mutation and natural selection shape the genetic variation in natural populations. Here, we directly estimated the spontaneous mutation rate by sequencing new Drosophila mutation accumulation lines maintained with minimal natural selection. We inferred strong stabilizing natural selection on quantitative traits because genetic variation among wild-derived inbred lines was much lower than predicted from a neutral model and the mutational effects were much larger than allelic effects of standing polymorphisms. Stabilizing selection could act directly on the traits, or indirectly from pleiotropic effects on fitness. However, our data are not consistent with simple models of mutation-stabilizing selection balance; therefore, further empirical work is needed to assess the balance of evolutionary forces responsible for quantitative genetic variation.



2014 ◽  
Author(s):  
Einar Árnason ◽  
Katrín Halldórsdóttir

A high-fecundity organisms, such as Atlantic cod, can withstand substantial natural selection and can at any time simultaneously replace alleles at a number of loci due to their excess reproductive capacity. High-fecundity organisms may reproduce by sweepstakes leading to highly skewed heavy-tailed offspring distribution. Under such reproduction the Kingman coalescent of binary mergers breaks down and models of multiple merger coalescent are more appropriate. Here we study nucleotide variation at the Ckma (Creatine Kinase Muscle type A) gene in Atlantic cod. The gene shows extreme differentiation between the North (Canada, Greenland, Iceland, Norway, Barents Sea) and the South (Faroe Islands, North-, Baltic-, Celtic-, and Irish Seas) with a between regions FST > 0.8 whereas neutral loci show no differentiation. This is evidence for natural selection. The protein sequence is conserved by purifying selection whereas silent and non-coding sites show extreme differentiation. Relative to outgroup the site-frequency spectrum has three modes, a mode at singleton sites and two high frequency modes at opposite frequencies representing divergent branches of the gene genealogy that is evidence for balancing selection. Analysis with multiple-merger coalescent models can account for the high frequency of singleton sites and indicate reproductive sweepstakes. Coalescent time scales with population size and with the inverse of variance in offspring number. Parameter estimates using multiple-merger coalescent models show fast time-scales. Time-scales of mitochondrial DNA are about square root of the effective population size and time-scales of nuclear genes are much faster.



2018 ◽  
Author(s):  
Alba Refoyo-Martínez ◽  
Rute R. da Fonseca ◽  
Katrín Halldórsdóttir ◽  
Einar Árnason ◽  
Thomas Mailund ◽  
...  

AbstractDetailed modeling of a species’ history is of prime importance for understanding how natural selection operates over time. Most methods designed to detect positive selection along sequenced genomes, however, use simplified representations of past histories as null models of genetic drift. Here, we present the first method that can detect signatures of strong local adaptation across the genome using arbitrarily complex admixture graphs, which are typically used to describe the history of past divergence and admixture events among any number of populations. The method—called Graph-aware Retrieval of Selective Sweeps (GRoSS)—has good power to detect loci in the genome with strong evidence for past selective sweeps and can also identify which branch of the graph was most affected by the sweep. As evidence of its utility, we apply the method to bovine, codfish and human population genomic data containing multiple population panels related in complex ways. We find new candidate genes for important adaptive functions, including immunity and metabolism in under-studied human populations, as well as muscle mass, milk production and tameness in specific bovine breeds. We are also able to pinpoint the emergence of large regions of differentiation due to inversions in the history of Atlantic codfish.



2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Paula S. Ramos ◽  
Stephanie R. Shaftman ◽  
Ralph C. Ward ◽  
Carl D. Langefeld

The reasons for the ethnic disparities in the prevalence of systemic lupus erythematosus (SLE) and the relative high frequency of SLE risk alleles in the population are not fully understood. Population genetic factors such as natural selection alter allele frequencies over generations and may help explain the persistence of such common risk variants in the population and the differential risk of SLE. In order to better understand the genetic basis of SLE that might be due to natural selection, a total of 74 genomic regions with compelling evidence for association with SLE were tested for evidence of recent positive selection in the HapMap and HGDP populations, using population differentiation, allele frequency, and haplotype-based tests. Consistent signs of positive selection across different studies and statistical methods were observed at several SLE-associated loci, includingPTPN22,TNFSF4,TET3-DGUOK,TNIP1,UHRF1BP1,BLK, andITGAMgenes. This study is the first to evaluate and report that several SLE-associated regions show signs of positive natural selection. These results provide corroborating evidence in support of recent positive selection as one mechanism underlying the elevated population frequency of SLE risk loci and supports future research that integrates signals of natural selection to help identify functional SLE risk alleles.



Author(s):  
Ailene MacPherson ◽  
Matthew J. Keeling ◽  
Sarah P. Otto

AbstractCoevolutionary negative frequency dependent selection has been hypothesized to maintain genetic variation in host and parasites. Despite the extensive literature pertaining to host-parasite coevolution, the effect of matching-alleles (MAM) coevolution on the maintenance of genetic variation has not been explicitly modelled in a finite population. The dynamics of the MAM in an infinite population, in fact, suggests that genetic variation in these coevolving populations behaves neutrally. We find that while this is largely true in finite populations two additional phenomena arise. The first of these effects is that of coevolutionary natural selection on stochastic perturbations in host and pathogen allele frequencies. While this may increase or decrease genetic variation, depending on the parameter conditions, the net effect is small relative to that of the second phenomena. Following fixation in the pathogen, the MAM becomes one of directional selection, which in turn rapidly erodes genetic variation in the host. Hence, rather than maintain it, we find that, on average, matching-alleles coevolution depletes genetic variation.



2021 ◽  
Author(s):  
Andy Fenton ◽  
Florencia Camus ◽  
Gregory D D Hurst

The majority of arthropod species carry facultative heritable microbes, bacteria that are passed from mother to offspring, and which may contribute to host function. These symbionts are coinherited down the maternal line with mitochondria, and selection favouring either new symbionts, or new symbiont variants, is known to drive loss of mitochondrial diversity as a correlated response. More recently, evidence has accumulated of episodic directional selection on mitochondria. We therefore examined the reciprocal interaction and model the impact of selection on mitochondrial DNA (mtDNA) on symbiont frequency. We performed this for three generic scenarios: a fixed benefit to the host carrying the symbiont, a benefit that decreased with symbiont frequency, and a benefit that increased with symbiont frequency. We find that direct selection on mtDNA can drive symbionts out of the population under some circumstances. Symbiont extinction occurs where the positively selected mtDNA mutation occurs initially in an individual that is uninfected with the symbiont, and the symbiont is initially at low frequency. When, in contrast, the positively selected mtDNA mutation occurs in a symbiont infected individual, the mutation becomes fixed and in doing so removes symbiont variation from the population. Given low frequency symbiont infections are common in natural populations, and selection on mtDNA is also considered to occur frequently, we conclude that mtDNA driven loss of symbionts represents a novel mechanism driving loss of facultative heritable microbes. We conclude further that the molecular evolution of symbionts and mitochondria, which has previously been viewed from a perspective of selection on symbionts driving the evolution of a neutral mtDNA marker, should be reappraised in the light of positive selection on mtDNA. Where low mtDNA and symbiont genetic diversity are observed, it should not be assumed to be a consequences of selection acting on the symbiont.



2021 ◽  
Vol 12 ◽  
Author(s):  
Manas Joshi ◽  
Adamandia Kapopoulou ◽  
Stefan Laurent

The unprecedented rise of high-throughput sequencing and assay technologies has provided a detailed insight into the non-coding sequences and their potential role as gene expression regulators. These regulatory non-coding sequences are also referred to as cis-regulatory elements (CREs). Genetic variants occurring within CREs have been shown to be associated with altered gene expression and phenotypic changes. Such variants are known to occur spontaneously and ultimately get fixed, due to selection and genetic drift, in natural populations and, in some cases, pave the way for speciation. Hence, the study of genetic variation at CREs has improved our overall understanding of the processes of local adaptation and evolution. Recent advances in high-throughput sequencing and better annotations of CREs have enabled the evaluation of the impact of such variation on gene expression, phenotypic alteration and fitness. Here, we review recent research on the evolution of CREs and concentrate on studies that have investigated genetic variation occurring in these regulatory sequences within the context of population genetics.



2017 ◽  
Author(s):  
Jiyun M. Moon ◽  
David M. Aronoff ◽  
John A. Capra ◽  
Patrick Abbot ◽  
Antonis Rokas

AbstractSialic acids are nine carbon sugars ubiquitously found on the surfaces of vertebrate cells and are involved in various immune response-related processes. In humans, at least 58 genes spanning diverse functions, from biosynthesis and activation to recycling and degradation, are involved in sialic acid biology. Because of their role in immunity, sialic acid biology genes have been hypothesized to exhibit elevated rates of evolutionary change. Consistent with this hypothesis, several genes involved in sialic acid biology have experienced higher rates of non-synonymous substitutions in the human lineage than their counterparts in other great apes, perhaps in response to ancient pathogens that infected hominins millions of years ago (paleopathogens). To test whether sialic acid biology genes have also experienced more recent positive selection during the evolution of the modern human lineage, reflecting adaptation to contemporary cosmopolitan or geographically-restricted pathogens, we examined whether their protein-coding regions showed evidence of recent hard and soft selective sweeps. This examination involved the calculation of four measures that quantify changes in allele frequency spectra, extent of population differentiation, and haplotype homozygosity caused by recent hard and soft selective sweeps for 55 sialic acid biology genes using publicly available whole genome sequencing data from 1,668 humans from three ethnic groups. To disentangle evidence for selection from confounding demographic effects, we compared the observed patterns in sialic acid biology genes to simulated sequences of the same length under a model of neutral evolution that takes into account human demographic history. We found that the patterns of genetic variation of most sialic acid biology genes did not significantly deviate from neutral expectations and were not significantly different among genes belonging to different functional categories. Those few sialic acid biology genes that significantly deviated from neutrality either experienced soft sweeps or population-specific hard sweeps. Interestingly, while most hard sweeps occurred on genes involved in sialic acid recognition, most soft sweeps involved genes associated with recycling, degradation and activation, transport, and transfer functions. We propose that the lack of signatures of recent positive selection for the majority of the sialic acid biology genes is consistent with the view that these genes regulate immune responses against ancient rather than contemporary cosmopolitan or geographically restricted pathogens.



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