Contrasted Polymorphism Patterns in a Large Sample of Populations From the Evolutionary Genetics Model <i>Drosophila simulans</i>

Selection, recombination, and the demographic history of a species can all have profound effects on genomewide patterns of variability. To assess the impact of these forces in the genome of Drosophila miranda, we examine polymorphism and divergence patterns at 62 loci scattered across the genome. In accordance with recent findings in D. melanogaster, we find that noncoding DNA generally evolves more slowly than synonymous sites, that the distribution of polymorphism frequencies in noncoding DNA is significantly skewed toward rare variants relative to synonymous sites, and that long introns evolve significantly slower than short introns or synonymous sites. These observations suggest that most noncoding DNA is functionally constrained and evolving under purifying selection. However, in contrast to findings in the D. melanogaster species group, we find little evidence of adaptive evolution acting on either coding or noncoding sequences in D. miranda. Levels of linkage disequilibrium (LD) in D. miranda are comparable to those observed in D. melanogaster, but vary considerably among chromosomes. These patterns suggest a significantly lower rate of recombination on autosomes, possibly due to the presence of polymorphic autosomal inversions and/or differences in chromosome sizes. All chromosomes show significant departures from the standard neutral model, including too much heterogeneity in synonymous site polymorphism relative to divergence among loci and a general excess of rare synonymous polymorphisms. These departures from neutral equilibrium expectations are discussed in the context of nonequilibrium models of demography and selection.

Section: Resultsmentioning

confidence: 99%

Selection, Recombination and Demographic History in Drosophila miranda

Bachtrog

Andolfatto

2006

“…In addition, synonymous site divergence along the Drosophila simulans lineage is particularly short ). The results in Figures 2 and 3 suggest that the proportions of rejections observed by Begun et al are not necessarily unexpected under neutrality particularly given estimated levels of recombination D. simulans (r/u $ 1, Andolfatto and Przeworski 2000), the small sample size used, the rela- tively low levels of synonymous site divergence along the D. simulans lineage and evidence for population structure and recent bottlenecks in this species (Wall et al 2002;Baudry et al 2006).…”

Section: T He Mcdonald-kreitman (Mk) Test Is a Widely Usedmentioning

confidence: 88%

Controlling Type-I Error of the McDonald–Kreitman Test in Genomewide Scans for Selection on Noncoding DNA

Andolfatto

2008

Departures from the assumption of homogenously interdigitated neutral and putatively selected sites in the McDonald-Kreitman test can lead to false rejections of the neutral model in the presence of intermediate levels of recombination. This problem is exacerbated by small sample sizes, nonequilibrium demography, recombination rate variation, and in comparisons involving more recently diverged species. I propose that establishing significance levels by coalescent simulation with recombination can improve the fidelity of the test in genomewide scans for selection on noncoding DNA. T HE McDonald-Kreitman (MK) test is a widely usedstatistical test of neutral model of evolution originally proposed for nonrecombining protein sequences (McDonald and Kreitman 1991;Nielsen 2005). The test compares within-species polymorphism and between-species divergence for two distinct classes of sites: synonymous sites, which are assumed to be neutral and nonsynonymous sites, which are putative targets of selection. The null model assumes that some fraction, f, of nonsynonymous sites is strongly deleterious and contributes negligibly to polymorphism and divergence. For the remaining nonsynonymous sites, (1 À f ), the ratio of polymorphism to divergence is expected to be identical to that for synonymous sites, if both behave according to the neutral model.Departures from expectations under neutral model are expected if nonsynonymous sites experience negative or positive selection. If the evolution of (nonlethal) nonsynonymous sites in a particular gene is largely governed by negative (or purifying) selection, this will tend to decrease the level of divergence at nonsynonymous sites more strongly than levels of polymorphism (Kimura 1983). The result will be that nonsynonymous sites will exhibit a higher ratio of polymorphism to divergence than putatively neutral synonymous sites. In contrast, if the evolution of nonsynonymous sites is governed primarily by positive selection, this will tend to decrease the ratio of polymorphism to divergence relative to synonymous sites. A departure from the neutral expectation in either direction can be detected by applying a standard statistical test to a 2 3 2 contingency table of polymorphism and divergence counts for synonymous and nonsynonymous sites.An attractive feature of the MK test is that the inference of selection, although not necessarily its mode, is remarkably robust to assumptions about nonequilibrium demography (Nielsen 2001;Eyre-Walker 2002) and recombination rates (Sawyer and Hartl 1992). In the absence of recombination, this robustness stems from the fact that all surveyed sites share the same genealogy and thus the entries of the 2 3 2 table are sufficient statistics (Nielsen 2001). In the presence of recombination, the robustness of the MK test is largely owed to the fact that nonsynonymous and synonymous sites are homogenously interdigitated in protein sequences ( Figure 1A).Using synonymous (or other neutral sites) to test for selection in linked noncoding DNA: Althoug...

“…Our simulations predict a pooling effect over a wide range of migration rates, implying one way to test the null hypothesis of panmixia, i.e., that the genealogies of local samples are indistinguishable from those of scattered samples. Very few published studies have performed separate analyses of local population samples and the pooled sample consisting of several local samples, but many studies can, in principle, be used to test our predictions because several local samples have been included [Drosophila (Baudry et al 2004(Baudry et al , 2006Nolte and Schlö tterer 2008), humans (Marth et al 2004;Voight et al 2005;Keinan et al 2007;Garrigan et al 2007), and plants (Heuertz et al 2006;Pyhäjärvi et al 2007)]. Pool and Aquadro (2006) demonstrated the pooling effect in sub-Saharan D. melanogaster, as have several studies in plants (Ingvarsson 2005;Arunyawat et al 2007;Moeller et al 2007) and humans (e.g., Ptak and Przeworski 2002;Hammer et al 2003).…”

Section: Discussionmentioning

confidence: 99%

The Impact of Sampling Schemes on the Site Frequency Spectrum in Nonequilibrium Subdivided Populations

Städler

Haubold

Merino³

et al. 2009

199

296

Using coalescent simulations, we study the impact of three different sampling schemes on patterns of neutral diversity in structured populations. Specifically, we are interested in two summary statistics based on the site frequency spectrum as a function of migration rate, demographic history of the entire substructured population (including timing and magnitude of specieswide expansions), and the sampling scheme. Using simulations implementing both finite-island and two-dimensional stepping-stone spatial structure, we demonstrate strong effects of the sampling scheme on Tajima's D (D T ) and Fu and Li's D (D FL ) statistics, particularly under specieswide (range) expansions. Pooled samples yield average D T and D FL values that are generally intermediate between those of local and scattered samples. Local samples (and to a lesser extent, pooled samples) are influenced by local, rapid coalescence events in the underlying coalescent process. These processes result in lower proportions of external branch lengths and hence lower proportions of singletons, explaining our finding that the sampling scheme affects D FL more than it does D T . Under specieswide expansion scenarios, these effects of spatial sampling may persist up to very high levels of gene flow (Nm . 25), implying that local samples cannot be regarded as being drawn from a panmictic population. Importantly, many data sets on humans, Drosophila, and plants contain signatures of specieswide expansions and effects of sampling scheme that are predicted by our simulation results. This suggests that validating the assumption of panmixia is crucial if robust demographic inferences are to be made from local or pooled samples. However, future studies should consider adopting a framework that explicitly accounts for the genealogical effects of population subdivision and empirical sampling schemes.A LTHOUGH most (if not all) species are characterized by various degrees of population subdivision, population geneticists continue to employ models of panmictic populations of constant size (the neutral equilibrium, NE, model) when testing for selection and/ or demographic changes through time. Motivated by empirical data sets that were found to be incompatible with expectations under the NE model, recent largescale studies have employed coalescent simulations of demographic changes such as bottlenecks and/or population expansions in attempts to estimate parameters of such (arguably) biologically more realistic scenarios (e.g., Marth et al. 2004;Nordborg et al. 2005;Ometto et al. 2005;Schmid et al. 2005;Heuertz et al. 2006;Li and Stephan 2006;Pyhäjärvi et al. 2007;Ross-Ibarra et al. 2008). However, such simulations still assume unstructured populations, while the empirical data may derive from subdivided species and a variety of sampling schemes. The data typically collected in such projects consist of multilocus DNA sequences from which genealogical information is extracted, e.g., on the number of segregating sites (S ), the average pairwise sequence diversity...