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Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.
PLoS Genet. 2011 Oct; 7(10):e1002326
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15 Nov 2011
Confirmation, New Finding
DOI: 10.3410/f.13370002.14740121
This study uses large-scale genome resequencing to investigate the long-standing issue of the genome-wide prevalence of positive and negative selection in the human genome. The authors find that recombination rates are positively correlated with diversity across the human genome, as seen before, but also...Continue reading
This study uses large-scale genome resequencing to investigate the long-standing issue of the genome-wide prevalence of positive and negative selection in the human genome. The authors find that recombination rates are positively correlated with diversity across the human genome, as seen before, but also that regions of low recombination tend to show an excess of rare variants. The simulation results suggesting a fit with models of weak negative selection provide another angle to the growing evidence that 'classic' signals of positive selection are rare in the human genome, suggesting that, compared with some organisms such as Drosophila, humans have experienced relatively few bouts of species-wide positive selection.
The simulations also highlight the important point that correlations between recombination and human-chimp divergence can be obtained due to historical selective sweeps, even in the absence of mutation rate differences between regions of high and low recombination.
The simulations also highlight the important point that correlations between recombination and human-chimp divergence can be obtained due to historical selective sweeps, even in the absence of mutation rate differences between regions of high and low recombination.
Disclosures
None declared
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Wright S: F1000Prime Recommendation of [Lohmueller KE et al., PLoS Genet 2011, 7(10):e1002326]. In F1000Prime, 15 Nov 2011; DOI: 10.3410/f.13370002.14740121. F1000Prime.com/13370002#eval14740121
F1000Prime Recommendations, Dissents and Comments for [Lohmueller KE et al., PLoS Genet 2011, 7(10):e1002326]. In F1000Prime, 18 May 2013; F1000Prime.com/13370002
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A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.
DOI: 10.1371/journal.pgen.1002326
PMID: 22022285
