The maintenance of genetic variance in fitness and the maintenance of sexual reproduction represent two mainstay evolutionary challenges that may, to some extent, have the same solution: sex-specific selection. Sex-specific selection inevitably leads to sexually antagonistic (SA) selection, which can maintain balanced polymorphisms for fitness (where alternative alleles pose opposite fitness effects in the two sexes). Alternatively, if/when the same alleles are favored in both sexes (i.e. sexually concordant (SC) selection) then sex-specific selection can account for the cost of sexual reproduction by enabling more efficient purifying selection via males at a negligible cost to population growth. At face value, these two processes seem at odds, but they likely act on largely independent sources of genetic variance, and therefore different loci in the genome. In order to fully understand how and why genetic variance and sexual reproduction are maintained so ubiquitously we need to study the mechanisms that enable the above processes to ensue. Current research foci are highlighted below. I study these and other questions using a broad range of techniques, including quantitative/statistical genetics, experimental evolution, genomics, transcriptomics, molecular genetics, and mathematical modeling.
Sexual conflict in the genome
Sexually antagonistic (SA) selection can generate balancing selection at loci underlying fitness, and therefore maintain genetic variance in fitness. However, theory shows that strictly additive SA polymorphisms on their own (without any additional mechanism) are vulnerable to becoming fixed for the more strongly selected allele. There are ca. 10 different mechanisms that can assist the stable maintenance of SA genetic variation. One of the most effective is sex-specific dominance reversal (SSDR), whereby the allele that benefits a given sex is also dominant in that sex. Dominance reversals enable heterozygotes to exhibit higher-than-intermediate fitness, which translates to a net heterozygote advantage at the population level and protects either allele from being lost.
There is now growing theoretical and empirical evidence for SSDR. As part of my PhD, I produced the first evidence of SSDR for the genetic variation underlying fitness, and the evidence points to it applying broadly throughout the genome of the seed beetle Callosobruchus maculatus (Grieshop and Arnqvist 2018). I am developing this method further (R package “DomRev” hopefully out soon) so that any diallel data set can be used to test for dominance reversals in loci underlying pairs of traits. Currently, I am using an evolve-and-resequence approach in Drosophila melanogaster to manipulate the sex-specific inheritance of whole chromosomes and reveal SA polymorphic sites in the genome. This genomic data will be combined with transcriptomic data to relate evolved differences in sex-biased gene expression to evolved changes in the genome. Future plans involve using allele-specific expression data and CRISPR/Cas9 genome editing to test for, and identify the mechanisms of, SSDR in candidate SA polymorphic genes.
Sex differences in (allele-specific) gene expression brought on by certain combinations of sex-specific trans-acting proteins, their concentrations, and/or cis-acting SNPs in their regulatory regions may be a common means by which SSDR is achieved. Currently, I am building a biophysical model of the gene regulatory machinery that could mediate/enable SSDR. The hope is that this will guide genomic and transcriptomic studies of SA genetic variation by showing which biologically explicit mechanisms are capable of mediating SSDRs, and therefore which genomic and transcriptomic patterns represent the signature of balanced SA polymorphisms. Such a bottom-up approach to detecting SA polymorphisms in the genome is an exciting new alternative to the current GWAS, gene expression, and genome-scan approaches because it side-steps one of the phenomena that obfuscates detection by those methods (i.e. dominance effects) whilst utilizing those dominance effects as the signature of interest. I have several ongoing projects that together represent a highly multidisciplinary effort to found and refine this bottom-up approach - blending quantitative genetics, genomics, transcriptomics, theory, molecular genetics, and genome editing.
Sexually reproducing females typically pay the so called two-fold cost of sex in that their male offspring do not produce any offspring themselves. So why is sexual reproduction the predominant mode of reproduction among eukaryotes? There are many explanations (e.g. recombination facilitates purifying selection against deleterious mutations), but one particularly under-explored hypothesis is that sexual reproduction enables very strong selection acting on males to purify the mutation load from the population at a negligible cost to population growth. That is, males carrying too many deleterious mutations would have almost zero fitness - purifying those mutations out of the population with little or no consequence to population growth because, again, males don’t directly contribute to offspring production. Thus, the precise nature of the cost of sex may actually enable one of its greatest benefits. For this benefit to actually pay off requires that (1) selection act more strongly via males than females, and (2) that the mutations that are selectively disadvantageous to males would also pose detriments to female/population offspring production. We know that selection does typically act more strongly via males than females, however, the extent to which this can facilitate the purging of mutation load depends on the extent to which selection targets SC versus SA genetic variation.
These predictions have been tested primarily by inducing mutations with ionizing radiation or other mutagens to see if those mutations are (1) selected against more strongly in males than females, and (2) detrimental to both male fitness and female/population offspring production. Colleagues and I have found support for these predictions using ionizing radiation (e.g. Grieshop et al. 2016), but this question remains under-explored with regard to natural standing genetic variation. I am currently reanalyzing some diallel data (mentioned above) in this light using sex-specific measures of heterosis - i.e. the increase in fitness of hybrids between two inbred strains relative to that of the inbred parent strains themselves. Heterosis is presumably attributable to, and therefore a measure of, the relative share of the mutation load in those parental genomes, which enables tests of the relationship between sex-specific outbred fitness and the mutation load carried in their genomes (with careful statistical consideration). Such studies get at the root of the remaining unresolved issues surrounding the role of sex-specific selection in accounting for the prevalence of sexual reproduction.