Is the X chromosome a hot spot for sexually antagonistic polymorphisms? Biases in current empirical tests of classical theory

Růžička, Filip; Connallon, Tim

doi:10.1098/rspb.2020.1869

Cited by 28 publications

(49 citation statements)

References 84 publications

(166 reference statements)

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“…The total number of loci is relatively small however, which may limit power to identify such biases if they exist. We also did not find any examples of SA loci on the X-chromosome, which may or may not be a hotspot of sexual antagonism (Fry, 2010; Rice, 1984; Ruzicka and Connallon, 2020). This was expected given that it is commonly not included in genome-wide analyses (Wise et al, 2013), although most of the papers we reviewed were candidate gene studies.…”

Section: Discussionmentioning

confidence: 52%

Systematic review reveals multiple sexually antagonistic polymorphisms affecting human disease and complex traits

Harper

Janicke

Morrow

2020

Preprint

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Sex differences in human disease risk and incidence are widely documented but their origins are poorly understood. An evolutionary model for differential disease risk between the sexes posits that alleles that are a risk factor (deleterious) in one sex may actually be protective (beneficial) in the opposite sex, and as such these sexually antagonistic (SA) alleles may be maintained in the population at frequencies higher than expected under purifying selection against unconditionally deleterious alleles. Sexual antagonism at genetic loci is thought to arise due to fundamental differences in how Darwinian fitness is maximized in the two sexes. Evidence for the occurrence of SA alleles comes from a number of non-human vertebrate and invertebrate models, which indicate they are common, although only very few specific SA loci have been identified. While there are many examples of loci with sex-limited effects in humans, there are no known examples of specific genetic variants that experience opposing patterns of selection between the sexes in humans. We hypothesized that this may be due to a mismatch in terminology between scientific disciplines rather than a genuine lack of examples. We therefore undertook a two-stage review of the literature for evidence of genetic polymorphisms in human disease and complex traits that exert their effects in a SA pattern, extracting effect sizes and allele frequencies where possible. In the first stage, we used search terms from evolutionary biology that aimed to identify examples of genes specifically referred to as having SA effects or were implicated in intralocus sexual conflict. In the second, we used terminology that was designed to capture as many examples as possible from the biomedical literature (e.g. sex-dependent, sex-opposite, men/women, boys/girls), which may have been missed in the first stage due to differences in terminology between the disciplines. The two searches gave very different results. The first stage returned 34 papers in total, none of which included evidence from humans of genetic loci with opposite effects on the two sexes. The second stage returned 881 papers, which after screening resulted in 70 papers, 32 were deemed eligible, and described 51 different genetic loci or haplotypes with sex-opposite effects on complex traits or disease. Of these, 22 loci increase disease risk or severity in one sex but are protective in the other. These loci may therefore be considered SA loci if the effects on disease risk translate into marginal effects on fitness through fecundity selection or mortality, although in no case were they referred to in terms of sexual antagonism. As predicted, alleles with net positive effects across the sexes occurred at a higher frequency than those with net negative effects. Our review reveals that significant long-term barriers to communication are occurring between scientific fields as a result of discipline-specific terminology. Less specific search terms revealed evidence that SA variants are maintained at relatively high frequencies in humans, apparently because while they contribute to the propensity for one sex to develop a range of diseases and disorders, they protect the other.

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Section: Discussionmentioning

confidence: 52%

Systematic review reveals multiple sexually antagonistic polymorphisms affecting human disease and complex traits

Harper

Janicke

Morrow

2020

Preprint

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“…Similarly, whilst it has been suggested that the X chromosome should be relatively enriched for sexually antagonistic polymorphisms in eumendelian systems as compared to the autosomes (Rice 1984), again this depends on assumptions about dominance (Fry 2010; Ruzicka and Connallon 2020). We find here that the same is true of comparisons between PGE and X chromosomes/arrhenotoky, with arrhenotokous organisms ones having a higher potential for polymorphism under parallel dominance, but a smaller space for polymorphisms under dominance reversals (see Supplementary Material).…”

Section: Discussionmentioning

confidence: 99%

“…We find here that the same is true of comparisons between PGE and X chromosomes/arrhenotoky, with arrhenotokous organisms ones having a higher potential for polymorphism under parallel dominance, but a smaller space for polymorphisms under dominance reversals (see Supplementary Material). Additionally, such sexually antagonistic polymorphisms may be easier to detect in some haplodiploid species as compared to eumendelian ones, because the asymmetric transmission genetics means that allele frequency differences that build up between the sexes in one generation, will carry over to the next (Crow and Kimura 1970; Ruzicka and Connallon 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Sexual antagonism is one such example, whereby genetic variants may prove beneficial to one sex but detrimental to the other. This has motivated a large body of theoretical work considering when such sexually antagonistic alleles will be able to invade (Owen 1953), how this may vary across the genome (Parsons 1961; Kidwell et al 1977; Rice 1984; Frank and Hurst 1996; Frank and Patten 2020; Hitchcock and Gardner 2020), and how we may be able to detect such alleles from population genetic data (Cheng and Kirkpatrick 2016; Kasimatis et al 2019; Ruzicka and Connallon 2020; Ruzicka et al 2020). This theory has been complemented more recently by molecular and quantitative genetic studies of laboratory and wild populations, both estimating the extent of sexual antagonism, and identifying specific loci at which sexually antagonistic alleles reside (Poissant et al 2010; Mank 2017; Rowe et al 2018; Connallon and Matthews 2019).…”

Section: Introductionmentioning

confidence: 99%

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Sexual antagonism in haplodiploids

Hitchcock

Gardner

Ross

2021

Preprint

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Females and males may face different selection pressures, such that alleles conferring a benefit in one sex may be deleterious in the other. Such sexual antagonism has received a great deal of theoretical and empirical attention, almost all of which has focused on diploids. However, a sizeable minority of animals display an alternative haplodiploid mode of inheritance, encompassing both arrhenotoky, whereby males develop from unfertilized eggs, and paternal genome elimination (PGE), whereby males receive but do not transmit a paternal genome. Alongside unusual genetics, haplodiploids often exhibit social ecologies that modulate the relative value of females and males. Here we develop a series of evolutionary-genetic models of sexual antagonism for haplodiploids, incorporating details of their molecular biology and social ecology. We find that: 1) PGE promotes female-beneficial alleles more than arrhenotoky, and to an extent determined by the timing of elimination - and degree of silencing of - the paternal genome; 2) sib-mating relatively promotes female-beneficial alleles, as do other forms of inbreeding, including limited male-dispersal, oedipal-mating, and the pseudo-hermaphroditism of Icerya purchasi; 3) resource competition between related females relatively inhibits female-beneficial alleles; and 4) sexual antagonism foments conflicts between parents and offspring, endosymbionts and hosts, and maternal-origin and paternal-origin genes.

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“… 2007 ; Lucotte et al. 2016 ) (but see Ruzicka and Connallon 2020 ). SA selection can lead to the evolution of sex‐biased gene expression (Connallon and Clark 2010 ), leading to sexual dimorphism (Lande 1980 ).…”

Section: Introductionmentioning

confidence: 98%

Experimental evolution reveals sex-specific dominance for surviving bacterial infection in laboratory populations ofDrosophila melanogaster

et al. 2021

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Males and females are subjected to distinct kinds of selection pressures, often leading to the evolution of sex‐specific genetic architecture, an example being sex‐specific dominance. Sex‐specific dominance reversals (SSDRs), where alleles at sexually antagonistic loci are at least partially dominant in the sex they benefit, have been documented in Atlantic salmon, rainbow trout, and seed beetles. Another interesting feature of many sexually reproducing organisms is the asymmetric inheritance pattern of X chromosomes, which often leads to distinct evolutionary outcomes on X chromosomes compared to autosomes. Examples include the higher efficacy of sexually concordant selection on X chromosomes, and X chromosomes being more conducive to the maintenance of sexually antagonistic polymorphisms under certain conditions. Immunocompetence is a trait that has been extensively investigated for sexual dimorphism with growing evidence for sex‐specific or sexually antagonistic variation. X chromosomes have been shown to harbor substantial immunity‐related genetic variation in the fruit fly, Drosophila melanogaster. Here, using interpopulation crosses and cytogenetic cloning, we investigated sex‐specific dominance and the role of the X chromosome in improved postinfection survivorship of laboratory populations of D. melanogaster selected against pathogenic challenge by Pseudomonas entomophila. We could not detect any contribution of the X chromosome to the evolved immunocompetence of our selected populations, as well as to within‐population variation in immunocompetence. However, we found strong evidence of sex‐specific dominance related to surviving bacterial infection. Our results indicate that alleles that confer a survival advantage to the selected populations are, on average, partially dominant in females but partially recessive in males. This could also imply an SSDR for overall fitness, given the putative evidence for sexually antagonistic selection affecting immunocompetence in Drosophila melanogaster. We also highlight sex‐specific dominance as a potential mechanism of sex differences in immunocompetence, with population‐level sex differences primarily driven by sex differences in heterozygotes.

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Is the X chromosome a hot spot for sexually antagonistic polymorphisms? Biases in current empirical tests of classical theory

Cited by 28 publications

References 84 publications

Systematic review reveals multiple sexually antagonistic polymorphisms affecting human disease and complex traits

Systematic review reveals multiple sexually antagonistic polymorphisms affecting human disease and complex traits

Sexual antagonism in haplodiploids

Experimental evolution reveals sex-specific dominance for surviving bacterial infection in laboratory populations ofDrosophila melanogaster

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