Deleterious variation shapes the genomic landscape of introgression
[['There is tremendous interest in quantifying the effects that demographic history has had on the patterns and dynamics of deleterious variation and genetic load [1–8] .', 'Several studies have suggested that recent human demography has had little impact on load [9 , 10] while others have suggested weak , but subtle , differences between human populations [11–15] .', 'All of these studies have typically focused on how population size changes , such as expansions and bottlenecks , have affected deleterious variation .', 'Other types of complex demography , however , have received considerably less attention .', 'In particular , gene flow may be important for shaping patterns of deleterious variation .', 'Population admixture , or hybridization between closely related species , appears to be quite common in nature [16] and has had a significant role in shaping human genomes [17] .', 'Gene flow alone can subtly change the effects of selection on deleterious variation [13] , but should have notable fitness consequences if deleterious variation is distributed differently between admixing populations .', 'For example , Neanderthals likely had a higher genetic load than coincident human populations due to the former’s smaller long-term population size [18 , 19] .', 'As a result , it is thought that gene flow from Neanderthals into the ancestors of modern humans could have increased the genetic load of some human populations by 0 . 5% [18] , and that linked selection removed much of Neanderthal ancestry from humans since that time .', 'In contrast , domesticated species likely have increased genetic load due to domestication bottlenecks and hitchhiking of deleterious alleles with artificially selected variants [20–22] .', 'Gene flow from wild populations could alleviate the genetic load of domesticated species , and increases in the frequency of wild-population ancestry should be observed in the domesticated population [23] .', 'Such changes in patterns of introgression are important to consider when studying how natural selection shapes the evolution of hybrid ancestry , a major goal in evolutionary biology .', 'Differences in the distribution of deleterious variation between hybridizing populations is one reason why natural selection may shape the evolution of hybrid ancestry .', 'Hybridization can also decrease the fitness of a population , for instance , if the parent lineages have diverged significantly and evolved genomic incompatibilities , or if parent lineages have evolved under unique and strong selective pressures in different environments .', 'In both cases , linked selection removes hybrid ancestry especially in regions of low recombination and high functional density [24–26] .', 'This creates genome wide , negative correlations between the local recombination rate , or functional density , and the frequency of introgressed ancestry , a pattern that is observed in humans [24 , 26 , 27] , swordtail fish [26] , and mice [28] .', 'The similar outcomes of both these processes mean that models of selection on deleterious variation should be considered before interpreting genomic patterns of introgression as evidence of divergence and speciation .', 'Another complication to studying the effects of deleterious mutations on introgression is that strongly deleterious new mutations are more likely to be fully or partially recessive [29–31] .', 'Furthermore , dominance coefficients vary between species .', 'New mutations in humans [14] are more likely to be additive than new mutations with the same selection coefficient in Arabidopsis [31] .', 'If some proportion of deleterious recessive variants is private to a population , admixed populations could experience heterosis when recessive variants are masked ( heterozygous ) in hybrid individuals [32] .', 'As a result , heterosis may participate in a tug-of-war on hybrid ancestry with additive variants by increasing the frequency of linked ancestry [18] , increasing apparent migration rates in regions linked to selected variants [33 , 34] , particularly when gene flow occurs in a highly structured population [35] .', 'Heterosis should also increase the probability that introgressed ancestry will persist in an admixed population , even if the introgressed ancestry contains more deleterious alleles [18] .', 'Given the extent to which hybridization is thought to be common to all species [16] , with levels of shared polymorphism in taxa such as Arabidopsis motivating arguments for the bifurcating species concept to be revoked [36] , it is crucial to understand the contribution of heterosis to patterns of hybrid ancestry .', 'Hybridization also transfers novel adaptive variants between evolutionarily distinct lineages [37] .', 'In humans , many Neanderthal variants are thought to be adaptive [38] , possibly affecting phenotypes such as skin pigmentation [39 , 40] , the response to oxygen levels at high altitudes [41] , and immunity to pathogens [42 , 43] .', 'In this case , the introduction of beneficial alleles via gene flow will also oppose the effect of linked selection from deleterious variation , since introgressed ancestry would increase in frequency by hitchhiking with adaptively introgressed variants .', 'Interestingly , North American populations of Drosophila melanogaster exhibit an overall enrichment for introgressed African ancestry in genomic regions of low recombination [44 , 45] .', 'The divergence time between these two D . melanogaster populations is small , and so selection on hybrid individuals may be driven by adaptive variants that arose over shorter time scales than genomic incompatibilities .', 'On the other hand , no correlation between recombination rate and introgression is observed in invasive Californian sunflowers [46] .', 'How selection against additive deleterious variation , selection for adaptive variants , and heterosis interact to determine these genomic patterns is unknown .', 'The objective of this study is to develop a clearer idea for null models of the dynamics of introgression in hybridizing populations while considering the effect of deleterious variants on fitness .', 'Specifically , we aim to understand how selection on introgressed ancestry is determined by differences in the effective population size , mating system , genome structure , recombination rate , distribution of fitness effects , and distribution of dominance coefficients .', 'Previous simulation and empirical work have shown that for at least some systems , deleterious variation is a significant modulator of gene flow [18 , 19 , 23 , 25 , 26] , but few studies have investigated these questions outside of demographic models specific to a system .', 'This study presents a series of simulations utilizing demographic models that generalize biological scenarios of interest by borrowing population genetic parameters and genomic structure from humans and Arabidopsis thaliana , two markedly different organisms with markedly different population genetic parameters .', 'We include realistic distributions of fitness effects and simulate under various models of dominance .', 'In addition , we examine how the relationship between the genomic landscape of introgressed ancestry and recombination rates or functional content is determined by the underlying demography .'], ['We used SLiM 3 . 0 [47] in conjunction with tools from pyslim [48] and msprime [49] to simulate a series of five models of admixture in the presence of deleterious variation .', 'Each of the five models was based on a divergence model where an ancestral population at equilibrium splits into two subpopulations .', 'At some time after the split , a single pulse of admixture occurs at a proportion of 5% , in one direction and for a single generation .', 'Due to practical considerations only an initial admixture proportion of 5% was simulated .', 'Fig 1 provides a cartoon representation of these models and the specific model parameters can be found in S1 Table .', 'All simulated sequence included genic structure ( exon/intron/intergenic regions ) , which was either randomly generated or incorporated from a reference genome as described in the following sections .', 'Only new nonsynonymous mutations were assigned nonzero selection coefficients , which were drawn from a gamma distribution of fitness effects ( DFE ) with shape parameter 0 . 186 and average selection coefficient E[s] = -0 . 01314833 [50] except when specified otherwise .', 'In other words , no positively selected mutations were simulated .', 'Throughout , we will refer to the subpopulation that migrants originate from as the donor subpopulation , and the subpopulation that migrants join as the recipient subpopulation .', 'Furthermore , we will refer to ancestry in the recipient subpopulation that originated in the donor subpopulation as introgression-derived ancestry .', 'We use pI to denote the total proportion of ancestry that is introgression-derived in the recipient subpopulation .', 'See the Methods for additional details on the simulations .', 'To better understand how deleterious variants shape patterns of introgressed ancestry , we first simulated small genomic segments with randomly generated genic structure , of length ~5 Mb and selection coefficients from a gamma DFE .', 'Two hundred simulation replicates using each of the 5 demographic models in Fig 1 ( parameters in S1 Table ) , each of the per base pair recombination rates r = 10−6 , 10−7 , 10−8 , and 10−9 , and additive ( h = 0 . 5 ) or recessive ( h = 0 . 0 ) fitness effects were generated , for a total 8 , 000 independent replicates .', 'In the 20 , 000 generations between the population split and admixture event , deleterious mutations accumulate at different rates across subpopulations for each unique model ( S1 Fig ) , illustrated by the relative difference in subpopulation fitness in Fig 2 .', 'We report subpopulation fitness while ignoring the deleterious variants that have fixed in both subpopulations , since selection will not act on globally monomorphic variants .', 'Because some weakly deleterious variants will fix in one subpopulation yet be lost in the other , each subpopulation’s fitness also steadily decreases through time .', 'In the additive fitness model , this relative difference in fitness is simply determined by relative differences in subpopulation size .', 'When there are no differences in subpopulation size ( Model 0 ) , the fitness of both donor and recipient subpopulations decreases at approximately the same rate ( wR ≈ wD , Fig 2 ) .', 'A similar pattern is observed for a short bottleneck in the recipient population ( wR ≈ wD , Model 1 , Fig 2 ) , reflecting the insensitivity of additive genetic load ( measured in terms of the number of deleterious variants per haplotype in S2 Fig ) to short-term changes in Ne [9] .', 'In contrast , long-term differences in population size ( Models 2–4 , Fig 2 ) provide enough time for deleterious variants to drift to higher frequency in the smaller subpopulation , resulting in substantial differences ( approximately 5% ) in fitness between subpopulations .', 'When deleterious mutations are recessive , a qualitatively similar relationship between subpopulation size and subpopulation fitness is generally observed .', 'When there are no differences in population size ( Model 0 ) , the fitness of donor and recipient subpopulations decreases at a similar rate ( wR ≈ wD , Fig 2 ) .', 'A short bottleneck in the recipient population ( Model', '1 ) increases the frequency of homozygous , recessive genotypes immediately post-bottleneck ( S3 Fig ) which slightly decreases the recipient subpopulation’s fitness immediately before admixture ( Fig 2 ) .', 'Finally , similar to the additive fitness model , long-term differences in population size result in substantial differences ( >10% ) in relative fitness between admixing populations .', 'The recombination rate is a key factor in determining differences in fitness between the two subpopulations .', 'When the recombination rate is low , the fitness of the smaller subpopulation decreases more quickly , reflecting the reduced efficacy of purifying selection in low recombination regions [51] .', 'Relative subpopulation differences in fitness between high recombination ( r = 10−6 ) and low recombination ( r = 10−9 ) simulations are about 2% for the additive fitness model and about 8% for the recessive fitness model .', 'Similar to the manner in which they affect subpopulation differences in fitness , recombination rates interact with demography to determine changes in subpopulation fitness after admixture .', 'When fitness effects are additive , admixture is unlikely to cause immediate and large changes in fitness , while subpopulation differences in fitness lead to gradual changes in fitness over time .', 'If admixing subpopulations have the same fitness ( Models 0 and 1 , Fig 2 and S1 Fig ) , admixture predictably has no impact on the recipient population’s fitness .', 'If donor haplotypes have lower fitness than the recipient ( Model 2 , Fig 2 ) , the recipient population’s fitness is negligibly decreased by admixture ( S2 Fig ) , specifically because relative differences in donor and recipient are small ( <10% ) and the initial frequency of donor ancestry is always 5% .', 'If instead the donor subpopulation has higher fitness ( Models 3 and 4 , Fig 2 ) , recipient fitness is relatively unaffected at the time of admixture but increases over time ( S2 Fig ) as the more fit haplotypes experience directional selection .', 'The velocity and magnitude of these changes depends on the recombination rate , as variants originating from the same subpopulation are generally selected in the same direction , and these variants remain on the same haplotypes when recombination is low .', 'When fitness effects are recessive , admixture instead causes immediate and large changes in fitness as recessive alleles are masked in heterozygous , hybrid individuals ( Fig 2 and S1 Fig ) .', 'The qualitative patterns observed are consistent across all demographic models , but the magnitude of these changes is significantly larger in simulations where the recipient subpopulation has lower fitness .', 'The recombination rate again plays a key role in determining fitness in the recipient subpopulation , with the largest changes in fitness occurring in simulations with low recombination .', 'This occurs because the largest differences in pre-admixture fitness are observed when recombination is low ( Fig 2 ) , but also because the heterozygosity of hybrids is maximized if recombination does not occur between donor and recipient haplotypes .', 'This linkage effect is particularly important as most of the variants under selection should have weak effects , since selection is likely to prevent strongly deleterious variants from drifting to high frequency even in a small population .', 'We next explore changes in the frequency of introgressed ancestry ( pI ) over time in the different models .', 'In the additive fitness case , changes in the frequency of introgression-derived ancestry are directly predictable from the differences in subpopulation fitness .', 'When there are no differences in load ( wR ≈ wD , Models 0 and 1 , Fig 2 and S1 Fig ) between mixing haplotypes , selection does not favor a particular ancestry and donor subpopulation ancestry remains , on average , at the initial admixture proportion of 5% in the recipient ( Fig 3 ) .', 'If donor subpopulation haplotypes have lower fitness as in Model 2 ( Fig 2 and S1 Fig ) deleterious donor ancestry is removed by selection , leading to a long-term pI of less than 5% .', 'If instead the donor subpopulation has higher fitness ( Models 3 and 4 , Fig 2 ) , pI is increased above 5% by selection .', 'This increase is greatest ( pI = 75% ) when there is an expansion after the time of admixture and in regions of low recombination ( Model 4 ) .', 'In a recessive fitness model , selection initially favors donor ancestry in the recipient subpopulation .', 'In all cases ( Models 0–4 , Fig 3 ) , the frequency of introgression-derived ancestry increases after admixture , regardless of whether the donor subpopulation’s fitness is less fit or more fit than the recipient .', 'This effect is explained by heterosis , which occurs when recessive deleterious variants are masked as heterozygotes in hybrid individuals ( S3 Fig ) , particularly in the generations immediately following admixture .', 'At this time point , recombination has had little chance to shuffle donor and recipient haplotypes and heterozygosity is maximized in admixed individuals .', 'Again , the recombination rate is a key parameter that determines patterns of introgressed ancestry .', 'As described previously , variants that are selected in the same direction remain linked when recombination is low ( r = 10−9 , Fig 3 ) , maximizing the effect of selection and minimizing selective interference between recombinant haplotypes .', 'When recombination is high ( r = 10−6 ) , the proportion of donor ancestry is unaffected by selection post-admixture ( long-term pI = 5% , Fig 3 ) , as recombination quickly decouples variants under selection from their ancestry backgrounds .', 'Importantly , when recombination rates are low ( r = 10−9 ) , the frequency of introgressed ancestry can increase substantially to up to 75% in the recipient population , despite the initial admixture proportion of 5% .', 'Even with higher recombination rates , when deleterious mutations are recessive and there is a population expansion at the time of admixture ( Model 4 ) , introgressed ancestry can increase up to 25% frequency .', 'So far , we have fixed the split time before admixture at 2N generations , a substantial time for differences in deleterious variation to accumulate between subpopulations .', 'To further examine the relationship between split time and selection on introgression-derived ancestry , we simulated with Models 0 and 4 but also varied the time between the split and admixture ( ts ) .', 'For simulations with a demography analogous to Model 0 , we simulated two divergent populations of equal size .', 'For those analogous to Model 4 , the recipient subpopulation’s size was reduced to 1 , 000 diploids immediately after the split and recovered to the original size at the same time that gene flow occurred .', 'The recombination rate was set to r = 10−9 in these simulations .', 'Fig 4 depicts the long-term proportion of introgressed ancestry , pI , 10 , 000 generations after the admixture event for these two sets of models .', 'We found that across our range of simulated ts , the long-term frequency of introgressed ancestry increases monotonically with ts regardless of the underlying demography .', 'Longer split times result in more deleterious variation being unique to each subpopulation , causing heterosis after admixture as private deleterious variants are masked by introgressed ancestry ( S4 Fig ) .', 'However , these differences appear to reach equilibrium after 20 , 000 generations ( Fig 4 ) , about when most deleterious variants are private to one subpopulation ( Fig 4 ) .', 'We also found as a bottleneck increases in duration , differences in subpopulation fitness become a significant contributor to the increase in long-term pI , but note the apparent equilibrium at 20 , 000 generations .', 'At a split time and thus bottleneck time of >20 , 000 generations , heterosis and differences in load increase long-term pI nearly 2-fold relative the model with no differences in load ( compare Model 0 to Model 4 in Fig 4 ) .', 'When parametrizing the population split times in terms of the realized FST values computed from the SNPs in the simulation output , we find that even for low levels of differentiation ( FST<0 . 05 ) , there is a pronounced increase in introgressed ancestry ( Fig 4 ) .', 'Interestingly , simulations with large long-term pI ( e . g . Model 4 at 1 , 000 generations or Model 0 at 5 , 000 generations ) can have a level of differentiation of FST<0 . 2 at the time of admixture , suggesting that even moderate levels of differentiation between subpopulations are sufficient to drive heterosis in low recombination regions ( Fig 4 ) .', 'So far , we have shown how selection on load shapes introgression-derived ancestry in a set of simple simulations .', 'However , recombination rates and gene density are heterogeneous across actual genomes , and our simulations suggest this variation also could influence the genomic landscape of introgression .', 'To investigate how a realistic genomic structure affects patterns of introgression , we simulated with three of the demographic models described previously ( Models 0 , 2 , and 4 ) using exon definitions and recombination map for a 100 Mb segment of human chromosome 1 .', 'We fixed the exon definitions and recombination map to be the same for all simulations .', 'Only new nonsynonymous mutations were assigned non-zero selection coefficients drawn from a gamma DFE .', 'In addition to simulating both additive and recessive fitness effects separately , we also simulated an inverse relationship between dominance coefficients and selection coefficients , which we will refer to as the h ( s ) relationship , using the function estimated by Henn et al . [14] .', 'We generated 100 simulation replicates for each of the three demographic models .', 'At the end of each simulation , we split the simulated chromosome into non-overlapping 100kb windows and computed the frequency of introgression-derived ancestry , exon density , and the average per base pair recombination rate in each window .', 'The frequency of introgression-derived ancestry generally exhibited genome-wide increases after admixture when mutations were partially or fully recessive and varied in accordance with differences in population size between subpopulations when mutations were additive .', 'In the model with equal subpopulation sizes ( Model 0 ) , we observed no average change in the frequency of introgression-derived ancestry when mutations were additive .', 'When new deleterious mutations were partially or fully recessive , we observed an overall genome-wide increase in the frequency of introgression-derived ancestry ( Fig 5 ) , with many regions reaching high frequency ( >50% ) in single simulation replicates ( S5 Fig ) .', 'This increase in frequency is only due to selection on recessive mutations and local variation in recombination rate , since no positively selected mutations were simulated .', 'In the model where introgressing haplotypes carried a larger deleterious burden ( Model 2 ) and when deleterious mutations were not all recessive , we observed an overall depletion of introgressed ancestry consistent with the effects of purifying selection upon introgressed ancestry ( Fig 5 ) .', 'However , in simulations with fully recessive mutations , the effects of heterosis were strong enough such that many genomic regions showed average increases in frequency of 1 . 5 to 2 times that of the initial introgression frequency of 5% .', 'Importantly , Harris and Nielsen [18] predicted that heterosis would increase the frequency of introgressed ancestry by only a few percent , but our simulations with a similar demographic model show that larger increases in the frequency of introgressed ancestry are possible , especially in exon-dense and low recombination regions .', 'Finally , when we simulated the introgression of haplotypes from a subpopulation with lower genetic load ( Model 4 ) , we observed drastic , genome-wide increases in the average frequency of introgressed ancestry in the recipient subpopulations ( Fig 5 ) as well as many fixed loci in individual simulations ( S5 Fig ) , regardless of whether fitness effects of mutations were additive or recessive .', 'For example , local regions of the simulated chromosome showed an average increase in introgressed ancestry from an initial frequency of 5% up to 50–60% frequency .', 'Furthermore , peaks of introgression are highly correlated between the simulations with different models of dominance , suggesting that the interplay between exon density and recombination strongly affects the way that selection acts on introgressed ancestry in this model .', 'This is the type of signature that is unlikely to be generated under neutral demographic models and could be mistakenly attributed to adaptive introgression .', 'It is also notable that the frequency of introgression-derived ancestry ( pI ) in each window appears to be driven not only by recombination but by exon density , or the local concentration of sites at which deleterious mutations can occur .', 'For recessive mutations , pI is greatly increased on the left-hand side of the simulated chromosome , which tends to be more gene-rich than the right-hand side of the chromosome ( Fig 5 and S5 Fig ) .', 'Importantly , the recombination rate was not significantly correlated with exon density ( Spearman’s ρ = -0 . 0457 , p = 0 . 149 ) in our simulations , showing these factors likely act independently to shape the landscape of introgression .', 'To more formally explore these relationships , we examine the correlations between genomic features and the average frequency of introgressed ancestry across 100 simulation replicates , measured in 100 kb windows ( Figs 6 and 7 ) .', 'In the model of equal subpopulation sizes ( Model 0 ) , the frequency of introgression-derived ancestry is not significantly related to the recombination rate or exon density when mutations have additive effects , but is positively correlated to exon density when fitness effects are fully or partially recessive ( Fig 7 ) .', 'The h ( s ) relationship results in intermediate levels of introgression relative to simulations with strictly additive or fully recessive new mutations .', 'For Model 2 , the frequency of introgression-derived ancestry is positively correlated to the recombination rate and negatively correlated to exon density when fitness is additive .', 'When fitness effects are fully recessive for this model , the frequency of introgressed ancestry is negatively correlated to recombination rate ( middle panel in middle row in Fig 6 ) and positively correlated to exon density ( middle panel in middle row in Fig 6 ) .', 'However , under the h ( s ) relationship , introgression derived ancestry is not significantly correlated to the recombination rate but is correlated with exon density .', 'Lastly , when introgressed ancestry comes from a larger subpopulation with a lower deleterious burden than the recipient subpopulation ( Model 4 ) , the frequency of introgression-derived ancestry is always negatively correlated with recombination rate , and positively correlated with exon density .', 'For Model 4 , these correlations are observed for all models of dominance .', 'Using these same simulations , we examined how selection on deleterious variation after admixture might influence the distribution of introgression deserts , or long stretches of the genome of the recipient population devoid of introgressed ancestry ( S6 Fig ) .', 'When subpopulation fitnesses are expected to be the same ( Model 0 ) , the distribution of introgression deserts for models with deleterious mutations is similar to a neutral model , suggesting that selection does not appreciably impact the distribution of deserts .', 'When introgression-derived ancestry is expected to be deleterious ( Model 2 ) , simulations with additive fitness are enriched for longer ancestry deserts , though only slightly so .', 'If instead introgression-derived ancestry is less deleterious than ancestry in the recipient population ( Model 4 ) , the length distribution of introgression deserts is shifted to be shorter , with the shortest introgression deserts occurring in models with recessive mutations ( h = 0 ) where both selection on load and heterosis act synergistically to increase the frequency of introgressed ancestry .', 'The observation that human X chromosomes are five-fold more resistant to introgression than the human autosome has been interpreted as a signature of genomic incompatibility between Neanderthals and humans , caused by an overrepresentation of male hybrid sterility genes on the X chromosome [24] .', 'However , the evolution of the X chromosome differs from the autosomes in a number of important aspects , particularly in the strength of selection on deleterious variants [52] , which may contribute to differences in patterns of introgression [18 , 19] .', 'It is additionally unclear how selection on recessive variants might contribute , or counteract , the apparent resistance of the X chromosome to introgression .', 'To investigate the expected patterns of introgression on the X chromosome , we modeled X chromosome admixture with the simulation framework previously described .', 'Although we used the same DFE for all these simulations , we utilized an analogous model of fitness that accounts for dosage compensation and the hemizygous sex [52 , 53] .', 'Chromosome structure , recombination rates , and the DFE were the same as the simulations of human chromosome 1 .', 'See Methods for additional details on the calculation of fitness in these simulations .', 'Our simulations show that deleterious variation alone can result in significant differences between introgression on the X and the autosomes ( Fig 8 ) .', 'When fitness is additive , stronger overall selection occurs on the X chromosome because males cannot be heterozygous .', 'This does not affect the X to autosome introgression ratio ( X/A ratio ) for Model 0 , since both populations carry a similar burden of deleterious variants .', 'For Model 2 , selection removes introgressed ancestry from the X more quickly ( X/A < 1 ) , and for Model 4 , selection increases the frequency of introgressed ancestry more on the X than on the autosomes ( X/A > 1 ) .', 'When fitness is recessive , the effect of heterosis is weaker for the X chromosome , since the hemizygous sex cannot be heterozygous .', 'This effect also results in less observed introgression on the X than the autosome ( X/A < 1 ) for all considered models .', 'Finally , under the h ( s ) relationship , our models predict amounts of introgression that are intermediate between strictly additive or strictly recessive models .', 'Human-like demography and genomic parameters may not generalize well for the purpose of understanding introgression in other species .', 'Functional density , recombination rates , effective population sizes , dominance , and the DFE can differ by an order of magnitude between species .', 'To provide an alternative picture of how introgression dynamics are driven by deleterious variation in a natural system where dominance and selection have been estimated , we simulated Models 0 , 2 , and 4 using the genomic structure of Arabidopsis thaliana .', 'While the simulated demography was similar to the ones described previously , we used exon definitions and a recombination map of most ( 29 . 1 out of 30 . 4 Mb ) of A . thaliana chromosome 1 , and chromosome structure was fixed to be the same in all 100 simulation replicates .', 'Both exon density and recombination rates are higher in A . thaliana ( medians of 100kb windows 4 . 8×10−1 and 3 . 2×10-8 , respectively ) than humans ( medians of 100kb windows 1 . 6×10−2 and 8 . 04×10−9 , respectively ) .', 'The ancestral population size was set to NA = 100 , 000 diploids , and the DFE to a gamma distribution with shape parameter 0 . 185 and E[s] = -0 . 0004866 [31] .', 'We also assumed that dominance coefficients followed the h ( s ) relationship estimated by Huber et al . and did not simulate scenarios with only additive or only recessive new mutations .', 'To the best of our knowledge , this is the only estimate of the h ( s ) relationship in a natural population other than humans .', 'We split the simulated chromosome into non-overlapping 100kb windows and computed the frequency of introgression-derived ancestry , exon density , and the average recombination rate in each window .', 'The genomic landscape of introgression in our simulated Arabidopsis population varied little ( Fig 9 ) , even in a single simulation replicate of the same demographic model ( S7 Fig ) .', 'For Model 0 , introgressed ancestry rose quickly from an initial frequency of 5% to about 24% , NA generations after admixture .', 'There was little spatial variation in the frequency of introgression-derived ancestry .', 'For example , pI did not appear to be affected by the paucity of exons near the centromere ( Fig 9 ) .', 'In Model 2 , introgression-derived ancestry was qui
['Introduction', 'Results', 'Discussion', 'Materials and methods']
['While it is appreciated that population size changes can impact patterns of deleterious variation in natural populations , less attention has been paid to how gene flow affects and is affected by the dynamics of deleterious variation .', 'Here we use population genetic simulations to examine how gene flow impacts deleterious variation under a variety of demographic scenarios , mating systems , dominance coefficients , and recombination rates .', 'Our results show that admixture between populations can temporarily reduce the genetic load of smaller populations and cause increases in the frequency of introgressed ancestry , especially if deleterious mutations are recessive .', 'Additionally , when fitness effects of new mutations are recessive , between-population differences in the sites at which deleterious variants exist creates heterosis in hybrid individuals .', 'Together , these factors lead to an increase in introgressed ancestry , particularly when recombination rates are low .', 'Under certain scenarios , introgressed ancestry can increase from an initial frequency of 5% to 30–75% and fix at many loci , even in the absence of beneficial mutations .', 'Further , deleterious variation and admixture can generate correlations between the frequency of introgressed ancestry and recombination rate or exon density , even in the absence of other types of selection .', 'The direction of these correlations is determined by the specific demography and whether mutations are additive or recessive .', 'Therefore , it is essential that null models of admixture include both demography and deleterious variation before invoking other mechanisms to explain unusual patterns of genetic variation .']
['Individuals from distinct populations sometimes will produce fertile offspring and will exchange genetic material in a process called hybridization .', 'Genomes of hybrid individuals often show non-random patterns of hybrid ancestry across the genome , where some regions have a high frequency of ancestry from the second population and other regions have less .', 'Typically , this pattern has been attributed to adaptive introgression , where beneficial genetic variants are passed from one population to the other , or to genomic incompatibilities between these distinct species .', 'However , other mechanisms could lead to these heterogeneous patterns of ancestry in hybrids .', 'Here we use simulations to investigate whether deleterious mutations affect the patterns of introgressed ancestry across genomes .', 'We show that when ancestry from a larger population is added to a smaller population , the ancestry from the larger population dramatically increases in frequency because it carries fewer deleterious mutations .', 'This occurs even in the absence of beneficial mutations in either population .', 'Additionally , we show that differences in sex chromosome evolution relative to autosomes , or differences in mating system , can affect patterns of introgression in similar ways .', 'Our study argues that deleterious mutations should be included in population genetic models used to identify unusual regions of the genome that appear to be under selection in hybrids .']
['biotechnology', 'deletion mutation', 'engineering and technology', 'population genetics', 'brassica', 'simulation and modeling', 'mutation', 'plant science', 'model organisms', 'experimental organism systems', 'plant genomics', 'population biology', 'plants', 'research and analysis methods', 'arabidopsis thaliana', 'bioengineering', 'animal studies', 'plant genetics', 'introgression', 'heterosis', 'eukaryota', 'plant and algal models', 'natural selection', 'heredity', 'genetics', 'biology and life sciences', 'gene flow', 'genomics', 'evolutionary biology', 'plant biotechnology', 'evolutionary processes', 'organisms']