The Genetics of Human Adaptation: Hard Sweeps, Soft Sweeps, and Polygenic Adaptation

“The standard approaches to detecting selection in population genetic data have been strongly shaped by the classical hitch-hiking model explored in detail by Maynard Smith and Haigh [40].”

“These include signals of partial sweeps [20], reduced diversity at putatively neutral sites [28,29] and an excess of SNPs with extreme population differentiation (high FST) within genes (Figure 1A) [30].”

“Taken together, these observations are most easily explained by either widespread positive selection, or possibly by background selection against mildly deleterious alleles [29,32].”

“Moreover, polygenic adaptations that draw on standing variation may not be detectable by scanning the genome to identify regions with low heterozygosity (Hermisson and Pennings 2005; Przeworski et al. 2005; Pritchard and Di Rienzo 2010; Pritchard et al. 2010; Hernandez et al. 2011; Burke 2012).”

“A solution may lie in borrowing methods from both population and quantitative genetics (Pritchard et al., 2010).”

“Although some experiments have persisted long enough to observe a single winning allele at these loci, these represent experimental examples of nascent “soft sweeps”, whereby the ancestral allele was being replaced by multiple alleles simultaneously (Pritchard et al. 2010).”

“This should be particularly common in the evolution of polygenic traits, such as body size, where multiple traitaffecting alleles may be segregating in the population at any time (Pritchard et al. 2010).”

“These local and global processes defining the relevant extent of hierarchical nestedness in habitat extinction-recolonization dynamics have critical implications for the geographic scale at which adaptation occurs and the degree to which mutational input limits adaptation [41].”

“…selection) or through soft selective sweeps in which multiple adaptive haplotypes sweep through the population simultaneously and the effects on linked genetic variation are less pronounced than under hard sweeps (Hermisson and Pennings, 2005; Hancock et al. , 2010; Pritchard et al. , 2010).”

“The adaptive status of many smaller candidate signals also remains uncertain due to inconsistencies in results between studies that utilized the same data [14], and it is inherently more difficult to functionally validate candidate adaptive signals underlying complex polygenic traits compared to monogenic traits where…”

“…heritability of brain volume based on ten twin studies is .84 (Baare et al. 2001; Bartley et al. 1997; Betjemann et al. 2010; Carmelli et al. 1998; Geshwind et al. 2002; Hulshoff Pol et al. 2006; Panizzon et al. 2009; Pennington et al. 2000; Pfefferbaum et al. 2000; Posthuma et al. 2002a, b).”

“The selection tests employed in this study cover a variety of signatures of positive selection but are unable to detect soft sweeps acting on polygenic traits [104].”

“GP may offer a more thoughtful picture of complex traits (e.g., thermal adaptation), presumably regulated by many low-effect loci (Pritchard et al., 2010).”

“Polygenic adaptation in natural populations can be reached via weak allele frequency changes at multiple loci across the genome, where advantageous alleles exist at low to moderate frequencies (Pritchard et al. 2010; Fu & Akey 2013).”

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“15.1 (Claude 2008; R Core Team 2014).”

“…multiple haplotypes preceding the onset of selection, was introduced by multiple migrant haplotypes from other populations, or occurred by multiple independent mutation events [Innan and Kim, 2004, Hermisson and Pennings, 2005, Prezeworski et al., 2005, Pritchard et al., 2010, Berg and Coop, 2015].”

“However, polygenic selection often results in adaptation by shifting allele frequencies at many loci rather than fixation of alleles at single loci (Chevin and Hospital 2008; Pritchard et al. 2010).”

“Empirical studies have found only a few examples of variants that have undergone ‘‘hard sweeps’’, where a favored allele arises by mutation and increases to high frequency in a population [35,36].”

“Through population genomic analysis, we identified an evolutionary process of polygenic adaptation, in which gene frequency shifts across multiple loci can drive rapidly phenotypic evolution [32,33].”

“…with recent empirical and theoretical work arguing that selection on standing variation may play an important role in adaptation (Orr and Betancourt 2001; Hermisson and Pennings 2005; Przeworski et al. 2005; Pennings and Hermisson 2006a, 2006b; Hancock et al. 2010; Pritchard et al. 2010).”

“From evidence of selection to evidence of gene-culture coevolution A considerable number of genes seem to have been under positive selection in humans according to genome-wide scans looking for selective sweeps and other evidence of selection in the human lineage [61].”

“Recent population genetic analyses of human variation have shown that much of the recent local adaptation in humans may be caused by subtle changes in allele frequencies in many genes rather than strong changes in a few genes [18,19].”

“, 2013), and polygenic adaption is difficult to detect (Pritchard et al., 2010).”

“These research aims are likely to be tested in the near future thanks to an increasing interest in recent years in both polygenic adaptation (Berg & Coop, 2014; Boyle, Li, & Pritchard, 2017; Pritchard et al., 2010; Purcell et al., 2009; Yeaman, 2015) and urban ecology research (Alberti et al.”

“Similarly, in polygenic models of adaptation, where traits are controlled by many loci each of small effect, smaller differences in allele frequency are expected among diverging populations even at causal loci (Pritchard et al. 2010).”

“A critical aspect of these dense data is that they exhibit correlation among measurements at neighboring genomic regions that result from linkage disequilibrium (slatkin 2008, Pritchard et al. 2010).”

“It is important to recognize that genomic signatures of selection arise from historical selection events (Pritchard et al. 2010; Le Corre and Kramer 2012), and they might not contribute to variation in a trait under current conditions (Pritchard and Di Rienzo 2010; Brieuc et al. 2015; Ashraf et al.…”

“Work in this area has demonstrated that soft sweeps, or selection on standing variation, may often be found in cases of polygenic traits (Strasburg et al. 2012) and are expected to be common in human populations (reviewed by Pritchard et al. 2010).”

“That set of selective pressures in turn leads to a complex array of phenotypic changes, which can involve many different loci across the genome (Coop et al. 2009; Pritchard et al. 2010; Rockman 2012; Gompert et al. 2013).”

“We identified introgression in the specialists in the SSI radiation and generalist outgroup populations on both a genome-wide and local level using Treemix (95) and the fd statistic [(96); Fig.”

“However, hard sweeps are not the only way for short-term adaptation and soft sweeps, partial sweep and polygenic adaptation are expected to also play a crucial role (for a review, see Pritchard et al. 2010).”

“2011), while artificial selection results in low diversity within linkage blocks (Pritchard et al. 2010).”

“The process of adaptation is often divided into three separate modes: hard selective sweeps, soft selective sweeps and polygenic adaptation [1].”

“…this type of variation is produced by small allele frequency changes in multiple loci across the genome (Boyle et al., 2017; Csilléry et al., 2018; Pritchard et al., 2010); variation that is better preserved during bottlenecks by balancing or frequency-dependent selection than newly arisen…”

“[33,34]].”

“This type of selective sweep has been defined as soft selective sweep [7–9].”

“Cases of rapid adaptation (Hendry and Kinnison 1999; Hendry et al. 2000; Pritchard et al. 2010; Burke et al. 2014; Kopp and Matuszewski 2014)—so-called contemporary evolution (Thompson 1998; Hendry and Kinnison 2001; Bell et al. 2004; Lotterhos and Schaal 2014; Lucek et al. 2014)—often invoke the…”

“…reversion) could have been maintained at moderate frequencies in the ancestral mung-bean line if adaptation to lentil involved changes in polygenic quantitative traits, such that different multilocus genotype combinations were favored on each host (as in, Burke et al. 2010; Pritchard et al. 2010).”

“The lack of sweeps does not imply that adaptation was rare in recent human evolution, as instead, much of it may have been driven by selection on genetically complex traits, that is, traits with heritable variation arising from many segregating loci (Coop et al., 2009; Pritchard et al., 2010; Pritchard and Di Rienzo,…”

“Second, loci under selection will tend to behave distinctively, revealing atypical variation patterns (Luikart et al., 2003).”

“If the number is large, there is no difficulty reconciling existing observations (95).”

“Polygenic adaptation, after a shift in the fitness optimum, can occur rapidly while causal variants only undergo subtle changes in allele frequency.(11) After a transient period during which the mean of the trait changes directionally, a new optimum is reached and the effect of selection will then largely be to reduce…”

“Such a situation could arise from selection on pre-existing (standing) genetic variation, in which one or more SNPs conferring reduced AHR function exists in multiple haplotypes in the population prior to environmental change, and selection leads to fixation of multiple alleles (soft sweep [83-85]).”

“We expect this to create a temporary footprint similar to that of a partial sweep (Pennings and Hermisson 2006a,b; Pritchard et al. 2010; Ralph and Coop 2010).”

“Such selection may be much more predominant than species-wide selection from new mutations and may be the predominant source of adaptive evolution in humans (Pritchard et al. 2010).”

“These alleles do not necessarily reach fixation and the haplotype pattern corresponds to several partial selection signatures or multiple “partial sweeps” (Pritchard et al., 2010).”

“The evidence of selection can be masked in soft sweeps (Pritchard et al. 2010) and therefore be hard to detect using Tajima0s D, as this test is not very robust in such cases (Simonsen et al.”

“2011), and when populations are large, as for microbial pathogens such as malaria (Pennings and Hermisson 2006; Pritchard et al. 2010).”

“positively selected variants to have very different phenotype effects from neutral alleles, but it is not clear a-priori what that relationship should be or if it will be possible to reliably identify positively selected SNPs [50,51].”

“774 This is because changes in the mean value of a polygenic trait can be produced by modest shifts 775 in allele frequencies at large numbers of loci that have individually small effects, so the effects of 776 selection at any single locus may not be readily detectable (23, 149, 150, 185).”

““Adaptation traits” are complex and often polygenically controlled (Pritchard et al., 2011).”

“However, as adaptive traits are probably polygenic (Pritchard et al., 2010), the signature of selection may be difficult to detect unless more advanced analytical approaches, not applicable on our data type, are used (Daub et al.”

“…the intensity of the selective pressure on each of them was relaxed due to their limited individual role in shaping the adaptive phenotype (Pritchard and Di Rienzo 2010; Pritchard et al. 2010; Hernandez et al. 2011; Scheinfeldt and Tishkoff 2013; Jeong and Di Rienzo 2014; Schrider and Kern 2017).”

“…the expected genome- wide footprint resulting from natural selection would not be that of a classical hard sweep, but would rather involve a large number of causal variants, each with subtle allele frequency changes (Hermisson & Pennings, 2017; Pritchard et al., 2010; Pritchard & Rienzo, 2010).”

“Although further investigation is warranted as many complex traits may be polygenic ( 60 ) and it is difficult to prove causal relations between behavioral/ecological traits and genes under selection, the 7165 SNPs inferred to have evolved under parallel linked and recurrent selection overlapped…”

“At least qualitatively, this scenario would produce patterns of variation within the recipient species reminiscent of “soft” sweeps (Hermisson and Pennings 2005; Pritchard et al. 2010; Orr and Unckless 2014), as seen in Mytilus (Fraisse et al. 2014).”

“Recently, population geneticists have emphasized that adaptation may occur by slight allele frequency changes at many genes (polygenic adaptation), and each locus may show little signature of natural selection (Pritchard et al. 2010).”

“Subtle shifts may also be observed if the traits responding to OA are highly polygenic (Pritchard et al., 2010) and/or there is a redundant genetic architecture (Yeaman, 2015).”

“…studies suggest that allele frequency differentiation around the selected site can vary depending on both the type of selective sweep and the genetic background of a given quantitative trait (Hermisson and Pennings 2005; Pennings and Hermisson 2006; Pritchard et al. 2010; Cutter and Pay-seur 2013).”

“First, phenotypic evolution may generally depend on “oligogenic” changes involving few loci or “polygenic” changes involving many loci (Bell 2009; Pritchard et al. 2010).”

“The reasons for this discrepancy are not clear, but it has been cautioned that the simple model of a beneficial allele sweeping through a population until fixation may be the exception rather then the rule (Pritchard and Di Rienzo, 2010; Pritchard et al., 2010).”

“…the literature for 20 years, including whether or not they can be reliably distinguished from hard sweeps (Hermisson and Pennings 2005, 2017; Przeworski et al. 2005; Pennings and Hermisson 2006a,b, Pritchard et al. 2010; Messer and Petrov 2013; Jensen 2014; Garud et al. 2015; Schrider et al. 2015).”

“A subtler mechanism of adaptation is through polygenic selection, in which selection acts simultaneously on advantageous alleles at multiple loci (Pritchard et al. 2010).”

“The breadth of this evidence is important (Pritchard et al., 2010).”

“Lab experiments indicate that adaptation from standing genetic variation often involves many loci and occurs by modest changes in allele frequencies rather than allele substitutions (Teotonio et al. 2009; Burke et al. 2010; Pritchard et al. 2010).”

“Examples are incomplete sweeps, where the adaptive mutation is not fixed in the population, and soft sweeps, where more than one haplotype has swept through the population (Pritchard et al. 2010).”

“A number of approaches have been developed to detect selective sweeps in population genetic data, using a combination of methods based on LD or haplotype structure [17-21], background allele frequency spectrum from Poolseq data [22], as well as the interplay between recombination and ancestral variation [23].”

“1) What is the population genomic signature of cognitive evolution? Depending on the mode and tempo of evolution, the population genomic signature of evolutionary changes in phenotypes will vary (30, 31).”

“It is possible that many types of soft sweeps could have given rise to these observed patterns, including soft sweeps from standing genetic variation [19], soft sweeps from multiple de novo mutations [20], spatial soft sweeps [74,75], polygenic sweeps [76], and sweeps arising from periodic selection (such as the oscil…”

“…polygenic adaptation or « softsweeps » are expected to have a much less pronounced impact on local genetic variability than hard sweeps and hence being far less easy to identify by classical approaches aiming at detecting footprints of selection (e.g., Pritchard et al. 2010; Peter et al. 2012).”

“Given the pleiotropic effects of many genes and the polygenicity of most adaptive phenotypes (Barghi et al., 2019; Pritchard et al., 2010), it is apparent that the characterization of individual selected alleles has clear limitations in reaching the later goal.”