How Good Are Predictions of the Effects of Selective Sweeps on Levels of Neutral Diversity?

Selective sweeps are thought to play a significant role in shaping patterns of variability across genomes; accurate predictions of their effects are, therefore, important for understanding these patterns. A commonly used model of selective sweeps assumes that alleles sampled at the end of a sweep, and that fail to recombine with wild-type haplotypes during the sweep, coalesce instantaneously, leading to a simple expression for sweep effects on diversity. It is shown here that there can be a significant probability that a pair of alleles sampled at the end of a sweep coalesce during the sweep before a recombination event can occur, reducing their expected coalescent time below that given by the simple approximation. Expressions are derived for the expected reductions in pairwise neutral diversities caused by both single and recurrent sweeps in the presence of such within-sweep coalescence, although the effects of multiple recombination events during a sweep are only treated heuristically. The accuracies of the resulting expressions were checked against the results of simulations. For even moderate ratios of the recombination rate to the selection coefficient, the simple approximation can be substantially inaccurate. The selection model used here can be applied to favorable mutations with arbitrary dominance coefficients, to sex-linked loci with sex-specific selection coefficients, and to inbreeding populations. Using the results from this model, the expected differences between the levels of variability on X chromosomes and autosomes with selection at linked sites are discussed, and compared with data on a population of Drosophila melanogaster.

Ghosts of a Structured Past: Impacts of Ancestral Patterns of Isolation-by-Distance on Divergence-Time Estimation

Isolation-by-distance is a widespread pattern in nature that describes the reduction of genetic correlation between subpopulations with increased geographic distance. In the population ancestral to modern sister species, this pattern may hypothetically inflate population divergence time estimation due to allele frequency differences in subpopulations at the ends of the ancestral population. In this study, we analyze the relationship between the time to the most recent common ancestor and the population divergence time when the ancestral population model is a linear stepping-stone. Using coalescent simulations, we compare the coalescent time to the population divergence time for various ratios of the divergence time over the population size. Next, we simulate whole genomes to obtain single nucleotide polymorphisms (SNPs), and use the Bayesian coalescent program SNAPP to estimate divergence times. We find that as the rate of migration between neighboring demes decreases, the coalescent time becomes significantly greater than the population divergence time when sampled from end demes. Divergence-time overestimation in SNAPP becomes severe when the divergence-to-population size ratio < 10 and migration is low. Finally, we demonstrate the impact of ancestral isolation-by-distance on divergence-time estimation using an empirical dataset of squamates (Tropidurus) endemic to Brazil. We conclude that studies estimating divergence times should be cognizant of the potential ancestral population structure in an explicitly spatial context or risk dramatically overestimating the timing of population splits.

The Multispecies Coalescent in Space and Time

A key distinction between species tree inference under the multi-species coalescent model (MSC), and the inference of gene trees in sliding windows along a genome, is in the effect of genetic linkage. Whereas the MSC explicitly assumes genealogies to be unlinked, i.e., statistically independent, genealogies located close together on genomes are spatially auto-correlated. Here we use tree sequence simulations with recombination to explore the effects of species tree parameters on spatial patterns of linkage among genealogies. We decompose coalescent time units to demonstrate differential effects of generation time and effective population size on spatial coalescent patterns, and we define a new metric, “phylogenetic linkage,” for measuring the rate of decay of phylogenetic similarity by comparison to distances among unlinked genealogies. Finally, we provide a simple example where accounting for phylogenetic linkage in sliding window analyses improves local gene tree inference.

How good are predictions of the effects of selective sweeps on levels of neutral diversity?

ABSTRACTSelective sweeps are thought to play a significant role in shaping patterns of variability across genomes; accurate predictions of their effects are, therefore, important for understanding these patterns. A commonly used model of selective sweeps assumes that alleles sampled at the end of a sweep, and that fail to recombine with wild-type haplotypes during the sweep, coalesce instantaneously, leading to a simple expression for sweep effects on diversity. It is shown here that there can be a significant probability that a pair of alleles sampled at the end of a sweep coalesce during the sweep before a recombination event can occur, reducing their expected coalescent time below that given by the simple approximation. Expressions are derived for the expected reductions in pairwise neutral diversities caused by both single and recurrent sweeps in the presence of such within-sweep coalescence, although the effects of multiple recombination events during a sweep are only treated heuristically. The accuracies of the resulting expressions were checked against the results of simulations. For even moderate ratios of the recombination rate to the selection coefficient, the simple approximation can be substantially inaccurate. The selection model used here can be applied to favorable mutations with arbitrary dominance coefficients, to sex-linked loci with sex-specific selection coefficients, and to inbreeding populations. Using the results from this model, the expected differences between the levels of variability on X chromosomes and autosomes with selection at linked sites are discussed, and compared with data on a population of Drosophila melanogaster.

Ghosts of a structured past: Impacts of ancestral patterns of isolation-by-distance on divergence-time estimation

Isolation by distance is a widespread pattern in nature that describes the reduction of genetic correlation between subpopulations with increased geographic distance. In the population ancestral to modern sister species, this pattern may hypothetically inflate population divergence time estimation due to the potential for allele frequency differences in subpopulations at the ends of the ancestral population. In this study, we analyze the relationship between the time to the most recent common ancestor and the population divergence time when the ancestral population model is a linear stepping-stone. Using coalescent simulations, we compare the coalescent time to the population divergence time for various ratios of the divergence time over the product of the population size and the deme number. Next, we simulate whole genomes to obtain SNPs, and use the Bayesian coalescent program SNAPP to estimate divergence times. We find that as the rate of migration between neighboring demes decreases, the coalescent time becomes significantly greater than the population divergence time when sampled from end demes. Divergence-time overestimation in SNAPP becomes severe when the divergence-to-population size ratio < 10 and migration is low. We conclude that studies estimating divergence times be cognizant of the potential ancestral population structure in an explicitly spatial context or risk dramatically overestimating the timing of population splits.

Approximating the coalescent under facultative sex

Genome studies of facultative sexual species, which can either reproduce sexually or asexually, are providing insight into the evolutionary consequences of mixed reproductive modes. It is currently unclear to what extent the evolutionary history of facultative sexuals’ genomes can be approximated by the standard coalescent, and if a coalescent effective population size Ne exists. Here, I determine if and when these approximations can be made. When sex is frequent (occurring at a frequency much greater than 1/N per reproduction per generation, for N the actual population size), the underlying genealogy can be approximated by the standard coalescent, with a coalescent Ne ≈ N. When sex is very rare (at frequency much lower than 1/N), approximations for the pairwise coalescent time can be obtained, which is strongly influenced by the frequencies of sex and mitotic gene conversion, rather than N. However, these terms do not translate into a coalescent Ne. These results are used to discuss the best sampling strategies for investigating the evolutionary history of facultative sexual species.

Appropriate Assignment of Fossil Calibration Information Minimizes the Difference between Phylogenetic and Pedigree Mutation Rates in Humans

Studies that measured mutation rates in human populations using pedigrees have reported values that differ significantly from rates estimated from the phylogenetic comparison of humans and chimpanzees. Consequently, exchanges between mutation rate values across different timescales lead to conflicting divergence time estimates. It has been argued that this variation of mutation rate estimates across hominoid evolution is in part caused by incorrect assignment of calibration information to the mean coalescent time among loci, instead of the true genetic isolation (speciation) time between humans and chimpanzees. In this study, we investigated the feasibility of estimating the human pedigree mutation rate using phylogenetic data from the genomes of great apes. We found that, when calibration information was correctly assigned to the human–chimpanzee speciation time (and not to the coalescent time), estimates of phylogenetic mutation rates were statistically equivalent to the estimates previously reported using studies of human pedigrees. We conclude that, within the range of biologically realistic ancestral generation times, part of the difference between whole-genome phylogenetic and pedigree mutation rates is due to inappropriate assignment of fossil calibration information to the mean coalescent time instead of the speciation time. Although our results focus on the human–chimpanzee divergence, our findings are general, and relevant to the inference of the timescale of the tree of life.

The effects on neutral variability of recurrent selective sweeps and background selection

ABSTRACTLevels of variability and rates of adaptive evolution may be affected by hitchhiking, the effect of selection on evolution at linked sites. Hitchhiking can be caused either by selective sweeps or by background selection, involving the spread of new favorable alleles or the elimination of deleterious mutations, respectively. Recent analyses of population genomic data have fitted models where both these processes act simultaneously, in order to infer the parameters of selection. Here, we investigate the consequences of relaxing a key assumption of some of these studies – that the time occupied by a selective sweep is negligible compared with the neutral coalescent time. We derive a new expression for the expected level of neutral variability in the presence of recurrent selective sweeps and background selection. We also derive approximate integral expressions for the effects of recurrent selective sweeps. The accuracy of the theoretical predictions was tested against multilocus simulations, with selection, recombination and mutation parameters that are realistic for Drosophila melanogaster. In the presence of crossing over, there is approximate agreement between the theoretical and simulation results. We show that the observed relations between the rate of crossing over and the level of synonymous site diversity and rate of adaptive evolution in Drosophila are probably mainly caused by background selection, whereas selective sweeps and population size changes are needed to produce the observed distortions of the site frequency spectrum.

Matching loci surveyed to questions asked in phylogeography

Although mitochondrial DNA (mtDNA) has long been used for assessing genetic variation within and between populations, its workhorse role in phylogeography has been criticized owing to its single-locus nature. The only choice for testing mtDNA results is to survey nuclear loci, which brings into contrast the difference in locus effective size and coalescence times. Thus, it remains unclear how erroneous mtDNA-based estimates of species history might be, especially for evolutionary events in the recent past. To test the robustness of mtDNA and nuclear sequences in phylogeography, we provide one of the largest paired comparisons of summary statistics and demographic parameters estimated from mitochondrial, five Z-linked and 10 autosomal genes of 30 avian species co-distributed in the Caucasus and Europe. The results suggest that mtDNA is robust in estimating inter-population divergence but not in intra-population diversity, which is sensitive to population size change. Here, we provide empirical evidence showing that mtDNA was more likely to detect population divergence than any other single locus owing to its smaller N e and thus faster coalescent time. Therefore, at least in birds, numerous studies that have based their inferences of phylogeographic patterns solely on mtDNA should not be readily dismissed.