Goudet, J. | Search bioRxiv

bioRxiv2018

Assessing natural selection during range expansions: Insights from a spatially explicit ABC study

For at least 40 years now, evolutionary biologists have discussed the relative roles of natural selection and genetic drift in shaping the genetic composition of populations. Range expansions are of particular interest in this discussion: They normally occur over environmental gradients allowing local adaptation to take place, but the demographic properties of these expansions also potentiate genetic-drift effects, which may in turn randomly generate extreme changes in allele frequencies as populations expand in territory and numbers (i.e. allele surfing). Here, we address the detection and measurement of selection in such scenario using simulations. We mimic a range expansion over a variable selective gradient where individuals have in their genomes both loci that are neutral and loci determining a quantitative trait subject to selection. The responsiveness of summary statistics to the selective pressure is then assessed, and estimates of the selective pressure are made - based on these statistics - with approximate Bayesian computation (ABC). We observe that statistics related to isolation-by-distance patterns present a strong response to selection. This response can be used in ABC to estimate the strength of selection acting on the simulated populations with very reliable measures of estimability, regardless of the genetic architecture underlying the selected trait. Furthermore, these estimates are robust to noise produced by other genetic and demographic parameters such as heritability, mutation, migration and population-growth rates. This approach of taking into account the spatial dimension of differentiation in quantitative traits offers a promising avenue of investigation about the role of natural selection in range-expansion scenarios, with possible implementations in the study of natural cases, as well.

evolutionary biology↗

bioRxiv2017

Population Differentiation at the HLA Genes

Balancing selection is defined as a class of selective regimes that maintain polymorphism above what is expected under neutrality. Theory predicts that balancing selection reduces population differentiation, as measured by FST. However, balancing selection regimes in which different sets of alleles are maintained in different populations could increase population differentiation. To tackle this issue, we investigated population differentiation at the HLA genes, which constitute the most striking example of balancing selection in humans. We found that population differentiation of single nucleotide polymorphisms (SNPs) at the HLA genes is on average lower than that of SNPs in other genomic regions. However, this result depends on accounting for the differences in allele frequency between selected and putatively neutral sites. Our finding of reduced differentiation at SNPs within HLA genes suggests a predominant role of shared selective pressures among populations at a global scale. However, in pairs of closely related populations, where genome-wide differentiation is low, differentiation at HLA is higher than in other genomic regions. This pattern was reproduced in simulations of overdominant selection. We conclude that population differentiation at the HLA genes is generally lower than genome-wide, but it may be higher for recently diverged population pairs, and that this pattern can be explained by a simple overdominance regime.

genetics↗

bioRxiv2017

Complex genetic patterns in human arise from a simple range-expansion model over continental landmasses

Although it is generally accepted that geography is a major factor shaping human genetic differentiation, it is still disputed how much of this differentiation is a result of a simple process of isolation-by-distance, and if there are factors generating distinct clusters of genetic similarity. We address this question using a geographically explicit simulation framework coupled with an Approximate Bayesian Computation approach. Based on six simple summary statistics only, we estimated the most probable demographic parameters that shaped modern human evolution under an isolation by distance scenario, and found these were the following: an initial population in East Africa spread and grew from 4000 individuals to 5.7 million in about 132 000 years. Subsequent simulations with these estimates followed by cluster analyses produced results nearly identical to those obtained in real data. Thus, a simple diffusion model from East Africa explains a large portion of the genetic diversity patterns observed in modern humans. We argue that a model of isolation by distance along the continental landmasses might be the relevant null model to use when investigating selective effects in humans and probably many other species.

genetics↗

bioRxiv2016

A unified characterization of population structure and relatedness.

Many population genetic activities, ranging from evolutionary studies to association mapping to forensic identification, rely on appropriate estimates of population structure or relatedness. All applications require recognition that quantities with an underlying meaning of allelic identity by descent are not defined in an absolute sense, but instead are made \"relative to\" some set of alleles other than the target set. The early Weir and Cockerham FST estimate made explicit that the reference set of alleles was across independent populations. Standard kinship estimates have an implicit assumption that pairs of individuals in a study sample, other than the target pair, are unrelated, whereas other estimates assume alleles within individuals are not identical by descent. However, populations lose independence when there is migration between them, and when individuals in a study are related it is difficult to see how they can also be non-inbred. We have therefore re-cast our treatments of population structure, relatedness and inbreeding to make explicit that the parameters of interest involve differences of probabilities of identity by descent in the target and the reference sets of alleles and so can be negative. We take the reference set to be for the population from which study individuals have been sampled. We provide simple moment estimates of these parameters, phrased in terms of allele matching within and between individuals for relatedness and inbreeding, or within and between populations for population structure. A multi-level hierarchy of alleles within individuals, alleles between individuals within populations, and alleles between populations allows a unified treatment of relatedness and population structure. Our new estimates appear to be sensitive to rare or private variants, to give indications of the effects of natural selection, and to be appropriate for use in association studies.

genetics↗

bioRxiv2016

A Unified Characterization ofPopulation Structure and Relatedness

Many population genetic activities, ranging from evolutionary studies to association mapping to forensic identification, rely on appropriate estimates of population structure or relatedness. All applications require recognition that quantities with an underlying meaning of allelic identity by descent are not defined in an absolute sense, but instead are made \"relative to\" some set of alleles other than the target set. The early Weir and Cockerham FST estimate made explicit that the reference set of alleles was across independent populations. Standard kinship estimates have an implicit assumption that pairs of individuals in a study sample, other than the target pair, are unrelated, whereas other estimates assume alleles within individuals are not identical by descent. However, populations lose independence when there is migration between them, and when individuals in a study are related it is difficult to see how they can also be non-inbred. We have therefore re-cast our treatments of population structure, relatedness and inbreeding to make explicit that the parameters of interest involve differences of probabilities of identity by descent in the target and the reference sets of alleles and so can be negative. We take the reference set to be for the population from which study individuals have been sampled. We provide simple moment estimates of these parameters, phrased in terms of allele matching within and between individuals for relatedness and inbreeding, or within and between populations for population structure. A multi-level hierarchy of alleles within individuals, alleles between individuals within populations, and alleles between populations allows a unified treatment of relatedness and population structure. Our new estimates appear to be sensitive to rare or private variants, to give indications of the effects of natural selection, and to be appropriate for use in association studies.

genetics↗