Showing papers on "Genetic hitchhiking published in 2010"

Population differentiation as a test for selective sweeps

Abstract: Selective sweeps can increase genetic differentiation among populations and cause allele frequency spectra to depart from the expectation under neutrality. We present a likelihood method for detecting selective sweeps that involves jointly modeling the multilocus allele frequency differentiation between two populations. We use Brownian motion to model genetic drift under neutrality, and a deterministic model to approximate the effect of a selective sweep on single nucleotide polymorphisms (SNPs) in the vicinity. We test the method with extensive simulated data, and demonstrate that in some scenarios the method provides higher power than previously reported approaches to detect selective sweeps, and can provide surprisingly good localization of the position of a selected allele. A strength of our technique is that it uses allele frequency differentiation between populations, which is much more robust to ascertainment bias in SNP discovery than methods based on the allele frequency spectrum. We apply this method to compare continentally diverse populations, as well as Northern and Southern Europeans. Our analysis identifies a list of loci as candidate targets of selection, including well-known selected loci and new regions that have not been highlighted by previous scans for selection.

The efficacy of divergence hitchhiking in generating genomic islands during ecological speciation

Abstract: Genes under divergent selection flow less readily between populations than other loci. This observation has led to verbal "divergence hitchhiking" models of speciation in which decreased interpopulation gene flow surrounding loci under divergent selection can generate large regions of differentiation within the genome (genomic islands). The efficacy of this model in promoting speciation depends on the size of the region affected by divergence hitchhiking. Empirical evidence is mixed, with examples of both large and small genomic islands. To address these empirical discrepancies and to formalize the theory, we present mathematical models of divergence hitchhiking, which examine neutral differentiation around selected sites. For a single locus under selection, regions of differentiation do not extend far along a chromosome away from a selected site unless both effective population sizes and migration rates are low. When multiple loci are considered, regions of differentiation can be larger. However, with many loci under selection, genome-wide divergence occurs and genomic islands are erased. The results show that divergence hitchhiking can generate large regions of differentiation, but that the conditions under which this occurs are limited. Thus, speciation may often require multifarious selection acting on many, isolated and physically unlinked genes. How hitchhiking promotes further adaptive divergence warrants consideration.

Genetic hitchhiking versus background selection: the controversy and its implications

Abstract: The controversy on the relative importance of background selection (BGS; against deleterious mutations) and genetic hitchhiking (associated with positive directional selection) in explaining patterns of nucleotide variation in natural populations stimulated research activities for almost a decade. Despite efforts from many theorists and empiricists, fundamental questions are still open, in particular, for the population genetics of regions of reduced recombination. On the other hand, the development of the BGS and hitchhiking models and the long struggle to distinguish them, all of which seem to be a purely academic exercise, led to quite practical advances that are useful for the identification of genes involved in adaptation and domestication.

The distinctive footprints of local hitchhiking in a varied environment and global hitchhiking in a subdivided population.

Abstract: Loci with higher levels of population differentiation than the neutral expectation are traditionally interpreted as evidence of ongoing selection that varies in space. This article emphasizes an alternative explanation that has been largely overlooked to date: in species subdivided into large subpopulations, enhanced differentiation can also be the signature left by the fixation of an unconditionally favorable mutation on its chromosomal neighborhood. This is because the hitchhiking effect is expected to diminish as the favorable mutation spreads from the deme in which it originated to other demes. To discriminate among the two alternative scenarios one needs to investigate how genetic structure varies along the chromosomal region of the locus. Local hitchhiking is shown to generate a single sharp peak of differentiation centered on the adaptive polymorphism and the standard signature of a selective sweep only in those subpopulations in which the allele is favored. Global hitchhiking produces two domes of differentiation on either side of the fixed advantageous mutation and signatures of a selective sweep in every subpopulation, albeit of different magnitude. Investigating population differentiation around a locus that strongly differentiates two otherwise genetically similar populations of the marine mussel Mytilus edulis, plausible evidence for the global hitchhiking hypothesis has been obtained. Global hitchhiking is a neglected phenomenon that might prove to be important in species with large population sizes such as many marine invertebrates.

Genetic linkage and natural selection

Abstract: The prevalence of recombination in eukaryotes poses one of the most puzzling questions in biology. The most compelling general explanation is that recombination facilitates selection by breaking down the negative associations generated by random drift (i.e. Hill–Robertson interference, HRI). I classify the effects of HRI owing to: deleterious mutation, balancing selection and selective sweeps on: neutral diversity, rates of adaptation and the mutation load. These effects are mediated primarily by the density of deleterious mutations and of selective sweeps. Sequence polymorphism and divergence suggest that these rates may be high enough to cause significant interference even in genomic regions of high recombination. However, neither seems able to generate enough variance in fitness to select strongly for high rates of recombination. It is plausible that spatial and temporal fluctuations in selection generate much more fitness variance, and hence selection for recombination, than can be explained by uniformly deleterious mutations or species-wide selective sweeps.

Mutation and the evolution of recombination.

Abstract: Under the classical view, selection depends more or less directly on mutation: standing genetic variance is maintained by a balance between selection and mutation, and adaptation is fuelled by new favourable mutations. Recombination is favoured if it breaks negative associations among selected alleles, which interfere with adaptation. Such associations may be generated by negative epistasis, or by random drift (leading to the Hill-Robertson effect). Both deterministic and stochastic explanations depend primarily on the genomic mutation rate, U. This may be large enough to explain high recombination rates in some organisms, but seems unlikely to be so in general. Random drift is a more general source of negative linkage disequilibria, and can cause selection for recombination even in large populations, through the chance loss of new favourable mutations. The rate of species-wide substitutions is much too low to drive this mechanism, but local fluctuations in selection, combined with gene flow, may suffice. These arguments are illustrated by comparing the interaction between good and bad mutations at unlinked loci under the infinitesimal model.

The role of advantageous mutations in enhancing the evolution of a recombination modifier.

Abstract: Although the evolution of recombination is still a major problem in evolutionary genetics, recent theoretical studies have shown that recombination can evolve by breaking down interference (“Hill–Robertson effects”) among multiple loci. This leads to selection on a recombination modifier in a population subject to recurrent deleterious mutation. Here, we use computer simulations to investigate the evolution of a recombination modifier under three different scenarios of recurrent mutation in a finite population: (1) mutations are deleterious only, (2) mutations are advantageous only, and (3) there is a mixture of deleterious and advantageous mutations. We also investigate how linkage disequilibrium, the strength of selection acting on a modifier, and effective population size change under the different scenarios. We observe that adding even a small number of advantageous mutations increases the fixation rate of modifiers that increase recombination, especially if the effects of deleterious mutations are weak. However, the strength of selection on a modifier is less than the summed strengths had there been deleterious mutations only and advantageous mutations only.

Characterizing Recurrent Positive Selection at Fast-Evolving Genes in Drosophila miranda and Drosophila pseudoobscura

Abstract: Characterizing the distribution of selection coefficients in natural populations remains a central challenge in evolutionary biology. We resequenced a subset of 19 fast-evolving protein-coding genes in the sister species Drosophila miranda and D. pseudoobscura and their flanking regions to characterize the spatial footprint left by recurrent and recent selection. Consistent with previous findings, fast-evolving genes and their flanking regions show reduced levels of neutral diversity compared with randomly chosen genes, as expected under recurrent selection models. Applying a variety of statistical tests designed for the detection of selection at different evolutionary timescales, we attempt to characterize parameters of adaptive evolution. In D. miranda, fast-evolving genes generally show evidence of increased rates of adaptive evolution relative to random genes, whereas this pattern is somewhat less pronounced in D. pseudoobscura. Our results suggest that fast-evolving genes are not characterized by significantly different selection coefficients but rather a shift in the distribution of the rate of fixation.

Signatures of Recent Directional Selection Under Different Models of Population Expansion During Colonization of New Selective Environments

Abstract: A major problem in population genetics is understanding how the genomic pattern of polymorphism is shaped by natural selection and the demographic history of populations. Complex population dynamics confounds patterns of variation and poses serious challenges for identifying genomic imprints of selection. We examine patterns of polymorphism using computer simulations and provide analytical predictions for hitchhiking effects under two models of adaptive niche expansion. The population split (PS) model assumes the separation of a founding population followed by directional selection in the new environment. Here, the new population undergoes a bottleneck and later expands in size. This model has been used in previous studies to account for demographic effects when testing for signatures of selection under colonization or domestication. The genotype-dependent colonization and introgression (GDCI) model is proposed in this study and assumes that a small number of migrants carrying adaptive genotype found a new population, which then grows logistically. The GDCI model also allows for constant migration between the parental and the new population. Both models predict reduction in variation and excess of high frequency of derived alleles relative to neutral expectations, with and without hitchhiking. Under comparable conditions, the GDCI model results in greater reduction in expected heterozygosity and more skew of the site frequency spectrum than the PS model. We also find that soft selective sweeps (fixation of multiple copies of a beneficial mutation) occurs less often in the GDCI model than in the PS model. This result demonstrates the importance of correctly modeling the ecological process in inferring adaptive evolution using DNA sequence polymorphism.

The Effect of Recurrent Mutation on the Linkage Disequilibrium under a Selective Sweep

Abstract: A selective sweep describes the reduction of diversity due to strong positive selection. If the mutation rate to a selectively beneficial allele is sufficiently high, Pennings and Hermisson (2006a) have shown, that it becomes likely, that a selective sweep is caused by several individuals. Such an event is called a soft sweep and the complementary event of a single origin of the beneficial allele, the classical case, a hard sweep. We give analytical expressions for the linkage disequilibrium (LD) between two neutral loci linked to the selected locus, depending on the recurrent mutation to the beneficial allele, measured by $D$ and $\hat{\sigma_D^2}$, a quantity introduced by Ohta and Kimura (1969), and conclude that the LD-pattern of a soft sweep differs substantially from that of a hard sweep due to haplotype structure. We compare our results with simulations.

Indel segregating within introns in the chicken genome are positively correlated with the recombination rates.

Abstract: Insertions and deletions (Indel) are important sources of genetic diversity and phenotypic divergence. Many factors such as mutation, recombination, selection and genetic drift can jointly affect the indel distribution across the genome. Studies of the relationship between recombination and indel density can, to a certain extent, reflect the selective constrain on indel. Based on the improved genetic map, genome sequence assembly and the partial (0.25X) shotgun sequencing of three breeds of domestic chicken, we calculated the recombination rates and the indel density segregating within introns and intergenic for 4 Mb windows (n = 210). Regression analyses demonstrated that recombination rates are significantly correlated with intron indel density, but not with the intergenic indel density. After adjusted regional effect, the significant trend was remained. This implies that selection is an important factor to influence the indel distribution within introns in chicken genome. By contrast, the intergenic indel seem to be neutral. Since the intron indel density on Z chromosome is less than half of that on autosomes, we preliminarily deduced that genetic hitchhiking might be more important than background selection in producing the observed correlation. As these two processes are not mutually exclusive, it is most likely that both contribute somewhat to the observed pattern. In result similar to previous study, we also found SNP density is highly correlated with indel density. Based on this characteristic, a hypothesis suggested that there are common effects of mutation and/or selection on the occurrence of indel and point mutations. This hypothesis can not explain our observations.

Genetic variability in autochthonous Basques from Guipuzcoa: a view from MHC microsatellites

Abstract: P>Five short tandem repeats (STRs) located at human chromosome 6 were analysed in 97 autochthonous Basques from Guipuzcoa (northern Spain), with the aim of assessing the genetic relationships of Basques at a European scale, based on the variability of the major histocompatibility complex (MHC) region, and comparing the phylogenetic information obtained from STRs, and from HLA class I genes (HLA-A and HLA-B) for the same set of European populations. The integrative approach was focused on D6S265 and D6S2792, according to availability of population databases. F-ST genetic distances obtained from STRs and from HLA loci were very similar, thereby describing a comparable pattern of genetic structuring among the European populations. These findings were supported by results of the Mantel test of matrix correspondence (r = 0.796, P = 0.0022) and by significant correlations between the first two F-ST eigenvectors of STRs and HLA genes. Coinciding with previous phylogenetic studies, Basques showed substantial genetic differentiation within the European context, probably as a result of the impact of random genetic drift and high inbreeding levels for extended periods of isolation even from adjacent populations. Analysis of the geographical distribution of the allele frequencies revealed a great number of latitudinal frequency clines in both the MHC STRs and the HLA class I genes, which supports the notion of the post-glacial resettlement of Europe being a crucial factor in the genetic make-up of Europeans. Our results indicate that analysing the genetic variability of MHC microsatellites could be a suitable strategy in evaluating the role of evolutionary forces such as natural selection (because of genetic hitchhiking effect), genetic drift and gene flow in the maintenance of polymorphism at the MHC region, because STRs can efficiently complement the genetic information obtained from HLA genes.

Evolution of the ancestral recombination graph along the genome in case of selective sweep

Abstract: We consider the genome of a sample of n individuals taken at the end of a selective sweep, which is the fixation of an advantageous allele in the population. When the selective advantage is high, the genealogy at a locus under selective sweep can be approximated by a comb with n teeth. However, because of recombinations during the selective sweep, the hitchhiking effect decreases as the distance from the selected site increases, so that far from this locus, the tree can be approximated by a Kingman coalescent tree, as in the neutral case. We first give the distribution of the tree at a given locus. Then we focus on the evolution of this tree along the genome. Since this tree-valued process is not Markovian, we study the evolution of the Ancestral Recombination Graph along the genome in case of selective sweep.