Angela
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Matthew Hartfield, Thomas Bataillon
"Selective sweeps under dominance andself-fertilisation:
https://www.biorxiv.org/content/biorxiv/early/2018/05/09/318410.full.pdf
"[/FONT]Populations adapt by fixing beneficial mutations. As a mutation spreads, it drags30 linked neutral variation to fixation, reducing diversity around adaptive genes. This31 footprint is known as a ‘selective sweep’. Adaptive variants can appear either from32 a new mutation onto a single genotype; from recurrent mutation onto different33 genotypes; or from existing genetic variation. Each of these sources leaves subtly34 different selective sweep patterns in genetic data, which have been explored under35 simple biological cases"
[FONT="]"[/FONT]Classic hitchhiking models consider ‘hard’ sweeps, where the common ancestor58 of adaptive alleles occurs after its appearance [11]. Yet the last fifteen years have59 seen a focus on quantifying ‘soft’ sweeps, where the most recent common ancestor60 of the beneficial allele arose before the variant became selected for (reviewed in61 [11–13]). Soft sweeps can originate from beneficial mutations being introduced62 by recurrent mutation [14,15], or from existing standing variation that was either63 neutral or deleterious [16–22]. A key property of soft sweeps is that the beneficial64 variant is present on multiple genetic backgrounds as it sweeps to fixation, so65 different haplotypes are present around the derived allele."
[FONT="]"[/FONT]In a simulation study, Teshima and Prze73worski [33] determined how recessive mutations spend a long period of time at low74 frequencies, increasing the amount of recombination that acts on derived haplo75types, weakening signatures of ‘hard’ sweeps. Fully recessive mutations may need76 a long time to reach a high enough frequency so that they can be picked up by77 genome scans for adaptive loci [34]. Ewing et al. [35] have carried out a general78 mathematical analysis of dominance on ‘hard’ sweeps on genetic diversity. Yet the79 impact that dominance has on ‘soft’ sweeps has yet to be explored in depth."
[FONT="]"[/FONT]. Inspired by these works, we demonstrated how the general723 sweep models can be used to determine adaptation properties by applying them to724 the SLC24A5 gene in European humans. Overall, the sweep pattern best matches725 a classic ‘hard’ sweep signature (Table 2; Fig 10). However, since the derived
"allele is known to be present at a low frequency in Africa, it also appears that the727 derived allele was introduced into Eurasia at a sufficiently low frequency so that728 the resulting signature is equivalent to a ‘hard’ sweep, even if the mutation did not729 appear after out-of-Africa migration (Fig 10(c)). This analyses demonstrates how730 adaptive mutations arising from standing variation have to be present at a suffi731ciently high frequency (above the ‘accelerated’ f0,A given by Eq 5) to be reliably732 distinguished from classic hard sweeps. In addition, analysis of this specific sweep733 region also demonstrates the utility of combining model fitting of genetic diversity734 with other statistics (e.g., haplotype structure, phylogenetic relationships) to fully735 work out the evolutionary history of individual selective sweeps."
[FONT="]"[/FONT]One potential difficulty arising out of model analysis is that of estimating dom737inance coefficients. Sweep models where h was non-additive did not explain the738 data better than a co-dominant sweep. Nevertheless, there are several ad-hoc739 reasons why the underlying mutation is likely to be approximately co-dominant.740 Recessive hard sweeps appear similar to sweeps from standing variation (with a741 weaker reduction in diversity at linked regions) and are heterozygous for long pe742riods of time (Fig 3(a)). Hence the strong sweep signature, and high frequency743 of the derived allele in European populations, makes it unlikely for this muta744tion to be recessive. Similarly, strongly dominant mutations take a long period of745 time to fully fix, in contrast to the observed near-fixation of the derived SLC24A5746 SNP. It will be important to extent inference methods to more accurately quantify747 dominance of adaptive mutations. One promising approach could be to analyse748 singleton densities, which appear to differ under recessive and dominant sweeps."
[FONT="]I'm not so sure about their assumptions here. Last I read, the trace SLC24A5 in Africa was found to be the result of back migration.
[/FONT]
Matthew Hartfield, Thomas Bataillon
"Selective sweeps under dominance andself-fertilisation:
https://www.biorxiv.org/content/biorxiv/early/2018/05/09/318410.full.pdf
- "[FONT="]A major research goal in evolutionary genetics is to uncover loci experiencing adaptation from genomic sequence data. One approach relies on finding 'selective sweep' patterns, where segregating adaptive alleles reduce diversity at linked neutral loci. Recent years have seen an expansion in modelling cases of 'soft' sweeps, where the common ancestor of derived variants predates the onset of selection. Yet existing theory assumes that populations are entirely outcrossing, and dominance does not affect sweeps. Here, we develop a model of selective sweeps that considers arbitrary dominance and non-random mating via self-fertilisation. We investigate how these factors, as well as the starting frequency of the derived allele, affect average pairwise diversity, the number of segregating sites, and the site frequency spectrum. With increased self-fertilisation, signatures of both hard and soft sweeps are maintained over a longer map distance, due to a reduced effective recombination rate and faster fixation times of adaptive variants. We also demonstrate that sweeps from standing variation can produce diversity patterns equivalent to hard sweeps. Dominance can affect sweep patterns in outcrossing populations arising from either a single novel mutation, or from recurrent mutation. It has little effect where there is either increased selfing or the derived variant arises from standing variation, since dominance only weakly affects the underlying adaptive allele trajectory. Different dominance values also alters the distribution of singletons (derived alleles present in one sample). We apply models to a sweep signature at the SLC24A5 gene in European humans, demonstrating that it is most consistent with an additive hard sweep. These analyses highlight similarities between certain hard and soft sweep cases, and suggest ways of how to best differentiate between related scenarios. In addition, self-fertilising species can provide clearer signals of soft sweeps than outcrossers, as they are spread out over longer regions of the genome."[/FONT]
"[/FONT]Populations adapt by fixing beneficial mutations. As a mutation spreads, it drags30 linked neutral variation to fixation, reducing diversity around adaptive genes. This31 footprint is known as a ‘selective sweep’. Adaptive variants can appear either from32 a new mutation onto a single genotype; from recurrent mutation onto different33 genotypes; or from existing genetic variation. Each of these sources leaves subtly34 different selective sweep patterns in genetic data, which have been explored under35 simple biological cases"
[FONT="]"[/FONT]Classic hitchhiking models consider ‘hard’ sweeps, where the common ancestor58 of adaptive alleles occurs after its appearance [11]. Yet the last fifteen years have59 seen a focus on quantifying ‘soft’ sweeps, where the most recent common ancestor60 of the beneficial allele arose before the variant became selected for (reviewed in61 [11–13]). Soft sweeps can originate from beneficial mutations being introduced62 by recurrent mutation [14,15], or from existing standing variation that was either63 neutral or deleterious [16–22]. A key property of soft sweeps is that the beneficial64 variant is present on multiple genetic backgrounds as it sweeps to fixation, so65 different haplotypes are present around the derived allele."
[FONT="]"[/FONT]In a simulation study, Teshima and Prze73worski [33] determined how recessive mutations spend a long period of time at low74 frequencies, increasing the amount of recombination that acts on derived haplo75types, weakening signatures of ‘hard’ sweeps. Fully recessive mutations may need76 a long time to reach a high enough frequency so that they can be picked up by77 genome scans for adaptive loci [34]. Ewing et al. [35] have carried out a general78 mathematical analysis of dominance on ‘hard’ sweeps on genetic diversity. Yet the79 impact that dominance has on ‘soft’ sweeps has yet to be explored in depth."
[FONT="]"[/FONT]. Inspired by these works, we demonstrated how the general723 sweep models can be used to determine adaptation properties by applying them to724 the SLC24A5 gene in European humans. Overall, the sweep pattern best matches725 a classic ‘hard’ sweep signature (Table 2; Fig 10). However, since the derived
"allele is known to be present at a low frequency in Africa, it also appears that the727 derived allele was introduced into Eurasia at a sufficiently low frequency so that728 the resulting signature is equivalent to a ‘hard’ sweep, even if the mutation did not729 appear after out-of-Africa migration (Fig 10(c)). This analyses demonstrates how730 adaptive mutations arising from standing variation have to be present at a suffi731ciently high frequency (above the ‘accelerated’ f0,A given by Eq 5) to be reliably732 distinguished from classic hard sweeps. In addition, analysis of this specific sweep733 region also demonstrates the utility of combining model fitting of genetic diversity734 with other statistics (e.g., haplotype structure, phylogenetic relationships) to fully735 work out the evolutionary history of individual selective sweeps."
[FONT="]"[/FONT]One potential difficulty arising out of model analysis is that of estimating dom737inance coefficients. Sweep models where h was non-additive did not explain the738 data better than a co-dominant sweep. Nevertheless, there are several ad-hoc739 reasons why the underlying mutation is likely to be approximately co-dominant.740 Recessive hard sweeps appear similar to sweeps from standing variation (with a741 weaker reduction in diversity at linked regions) and are heterozygous for long pe742riods of time (Fig 3(a)). Hence the strong sweep signature, and high frequency743 of the derived allele in European populations, makes it unlikely for this muta744tion to be recessive. Similarly, strongly dominant mutations take a long period of745 time to fully fix, in contrast to the observed near-fixation of the derived SLC24A5746 SNP. It will be important to extent inference methods to more accurately quantify747 dominance of adaptive mutations. One promising approach could be to analyse748 singleton densities, which appear to differ under recessive and dominant sweeps."
[FONT="]I'm not so sure about their assumptions here. Last I read, the trace SLC24A5 in Africa was found to be the result of back migration.
[/FONT]