Abstract
Most human populations exhibit an excess of high‐frequency variants, leading to a U‐shaped site‐frequency spectrum (uSFS). This pattern has been generally interpreted as a signature of ongoing episodes of positive selection, or as evidence for a mis‐assignment of ancestral/derived allelic states, but uSFS has also been observed in populations receiving gene flow from a ghost population, in structured populations, or after range expansions. In order to better explain the prevalence of high‐frequency variants in humans and other populations, we describe here which patterns of gene flow and population demography can lead to uSFS by using extensive coalescent simulations. We find that uSFS can often be observed in a population if gene flow brings a few ancestral alleles from a well‐differentiated population. Gene flow can either consist in single pulses of admixture or continuous immigration, but different demographic conditions are necessary to observe uSFS in these two scenarios. Indeed, an extremely low and recent gene flow is required in the case of single admixture events, while with continuous immigration, uSFS occurs only if gene flow started recently at a high rate or if it lasted for a long time at a low rate. Overall, we find that a neutral uSFS occurs under more restrictive conditions in populations having received single pulses of gene flow than in populations exposed to continuous gene flow. We also show that the uSFS observed in human populations from the 1000 Genomes Project can easily be explained by gene flow from surrounding populations without requiring past episodes of positive selection. These results imply that uSFS should be common in non‐isolated populations, such as most wild or domesticated plants and animals.
Highlights
Allele frequency changes are driven by the combined action of different evolutionary forces such as mutation, selection, genetic drift and migration (Wright, 1931), but most of the variant frequencies are expected to be rare (Ewens, 1972), leading to a L-shaped site-frequency spectrum (SFS) (Fu, 1995)
An unexpectedly large proportion of high-frequency-derived alleles, resulting in U-shaped SFS, has been documented in multiple species, including wild and domesticated plants (Liu, Zhou, Morrell, Gaut, & Ge, 2017; Morton, Dar, & Wright, 2009; Price et al, 2018), animals (Cooper, Burrus, Ji, Hahn, & Montooth, 2015; de Manuel et al, 2016; Murray, HuertaSanchez, Casey, & Bradley, 2010) and even human populations (Henn et al, 2015; Pouyet, Aeschbacher, Thiéry, & Excoffier, 2018). Several explanations for these uSFS have been proposed. This phenomenon has been notably interpreted as a signature of positive selection at several loci (Akashi & Schaeffer, 1997; Bustamante, Wakeley, Sawyer, & Hartl, 2001), as neutral variants hitchhiking with beneficial mutations during selective sweeps would be observed at high frequencies (Andolfatto & Przeworski, 2001; Fay & Wu, 2000; Kim & Stephan, 2000, 2002; Lapierre, Blin, Lambert, Achaz, & Rocha, 2016; Pavlidis, Jensen, & Stephan, 2010; Stephan, 2016), leading to a uSFS (Hahn, 2018; Ronen, Udpa, Halperin, & Bafna, 2013)
Low-frequency-derived alleles mistakenly annotated as ancestral would lead to the emergence of high-frequency-derived variants and create a uSFS (Baudry & Depaulis, 2003; Hernandez, Williamson, & Bustamante, 2007). uSFS can emerge in multiple-merger coalescent models that have been developed to account for strong selective sweeps or a very large variance in reproductive success among individuals of a population (Eldon, Birkner, Blath, & Freund, 2015; Rice, Novembre, & Desai, 2018; Sargsyan & Wakeley, 2008; Tellier & Lemaire, 2014), which is not well accounted for in the classical Kingman coalescent framework
Summary
Allele frequency changes are driven by the combined action of different evolutionary forces such as mutation, selection, genetic drift and migration (Wright, 1931), but most of the variant frequencies are expected to be rare (Ewens, 1972), leading to a L-shaped site-frequency spectrum (SFS) (Fu, 1995). An unexpectedly large proportion of high-frequency-derived alleles, resulting in U-shaped SFS (uSFS), has been documented in multiple species, including wild and domesticated plants (Liu, Zhou, Morrell, Gaut, & Ge, 2017; Morton, Dar, & Wright, 2009; Price et al, 2018), animals (Cooper, Burrus, Ji, Hahn, & Montooth, 2015; de Manuel et al, 2016; Murray, HuertaSanchez, Casey, & Bradley, 2010) and even human populations (Henn et al, 2015; Pouyet, Aeschbacher, Thiéry, & Excoffier, 2018) Several explanations for these uSFS have been proposed. We have compared the likelihoods of these models for ten populations from the 1,000 Genomes panel where uSFS is observed
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