Biology subjects

Ming, M. J.

Publications and source records attributed to Ming, M. J..

4 recordsLinked to original sources

bioRxiv2026

Drivers of systemic male-female allele frequency divergence in humans

Allele frequency differences between males and females in genetic studies have been interpreted as suggestive of sex differences in natural selection. However, systemic differences may also arise through sex differences in study participation as well as bioinformatic artifacts. To mitigate these confounding effects, we performed a meta-analysis of sex differences in allele frequencies across three genetic studies. We identify twelve concordant genes with cross-study evidence of sex differences in allele frequency. Using previous literature about the twelve candidates, we propose four hypotheses for how and when sex differences in allele frequencies arise and suggest which hypotheses are plausible for each candidate. For example, beyond candidates that plausibly reflect sex differences in viability, we also find candidate loci potentially underlying fitness differences between X/Y-carrying sperm. Taken together, our results offer a clearer delineation of the factors driving sex differences in allele frequencies, including the timing and mechanisms of natural selection.

evolutionary biology↗

bioRxiv2024

Does Sex-Differential Gene Expression Drive Sex-Differential Selection in Humans?

Sex differences in human transcriptomes have been argued to drive sex-differential natural selection (SDS). Here, we show that previous evidence supporting this hypothesis has been largely unfounded. We develop a new method to test for a genome-wide relationship between sex differences in expression and selection on expression-influencing alleles (eQTLs). We apply it across 39 human tissues and find no evidence for a general relationship. We offer possible explanations for the lack of evidence, including that it is due in part to eQTL ascertainment bias towards sites under weak selection. We conclude that the drivers of ongoing SDS in humans remain to be identified.

evolutionary biology↗

bioRxiv2024

The battle of the sexes in humans is highly polygenic

Sex-differential selection (SDS), which occurs when the fitness effects of alleles differ between males and females, can have profound impacts on the maintenance of genetic variation, disease risk, and other key aspects of natural populations. Because the sexes mix their autosomal genomes each generation, quantifying SDS is not possible using conventional population genetic approaches. Here, we introduce a novel method that exploits subtle sex differences in haplotype frequencies resulting from SDS acting in the current generation. Using data from 300K individuals in the UK Biobank, we estimate the strength of SDS throughout the genome. While only a handful of loci under SDS are individually significant, we uncover polygenic signals of genome-wide SDS for both viability and fecundity. An interesting life-history tradeoff emerges: alleles that increase viability more in one sex increase fecundity more in the other sex. Lastly, we find evidence of SDS on fecundity acting on alleles affecting arm fat-free mass. Taken together, our findings connect the long-standing evidence of SDS acting on human phenotypes with its impact on the genome. Significance statementSelection often acts differently on females and males, as evidenced by the striking sexual dimorphism found in many taxa. As a result, alleles can have different fitness effects in each sex. Consequences can include higher levels of genetic variation and higher disease burdens in populations. This study introduces a novel method to quantify this sex-differential selection (SDS) and reveals that it acts throughout the human genome. We discovered a life history tradeoff between survival and fecundity in females and males and that SDS on fecundity acts on alleles affecting arm fat-free mass.

evolutionary biology↗

bioRxiv2022

Amplification is the Primary Mode of Gene-by-Sex Interaction in Complex Human Traits

Sex differences in complex traits are suspected to be in part due to widespread gene-by-sex interactions (GxSex), but empirical evidence has been elusive. Here, we infer the mixture of ways polygenic effects on physiological traits covary between males and females. We find that GxSex is pervasive but acts primarily through systematic sex differences in the magnitude of many genetic effects ("amplification"), rather than in the identity of causal variants. Amplification patterns account for sex differences in trait variance. In some cases, testosterone may mediate amplification. Finally, we develop a population-genetic test linking GxSex to contemporary natural selection and find evidence for sexually antagonistic selection on variants affecting testosterone levels. Taken together, our results suggest that the amplification of polygenic effects is a common mode of GxSex that may contribute to sex differences and fuel their evolution. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/490973v3_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@19c267eorg.highwire.dtl.DTLVardef@a32233org.highwire.dtl.DTLVardef@1a6daeorg.highwire.dtl.DTLVardef@116cbff_HPS_FORMAT_FIGEXP M_FIG C_FIG

genomics↗