Genome-wide study quantifies genetic “war between the sexes”

Humans and flies are still undergoing natural selection based on sex.

Genes with moderately different expression levels in males and females are subject to ongoing, sex-related natural selection, reports a new study by Changde Cheng and Mark Kirkpatrick at the University of Texas, Austin, published in PLOS Genetics.

Differences between males and females – whether humans or flies – come from differences in gene expression in the sexes, but exactly how evolution has shaped those differences is still a mystery. Scientists quantified the relationship between sex-biased expression, which are variations in gene expression between the sexes, and sex-specific selection, which is when natural selection favors different traits in different sexes, on a genome-wide scale in humans and flies. They observe a “Twin Peaks” pattern in both species where genes with intermediate differences in expression between the sexes are undergoing the greatest level of sex-specific selection, while genes that are either completely or not at all expressed differently undergo little selection. The pattern suggests that the “war between the sexes” is more than a metaphor: it contributes to measurable patterns in genes that affect mortality in humans.

The study’s results suggest that ongoing sex-specific selection commonly occurs in the genomes of humans and flies. These findings help inform our understanding of how differences between the sexes evolve, and factors affecting the evolution of entire genomes.

Graph depicting human autosomal genes with intermediate sex-biased expression
The strength of sex-specific selection is strongest on human autosomal genes with intermediate sex-biased expression. The white curve is the best-fit 4th degree polynomial and the intensity of red indicates the likelihood that the regression passes through a given value. The average FST for the SNPs in a gene is small at &#9651 = 0 (unbiased expression), increases to a peak as sex-bias grows, then decreases as &#9651 approaches -1 and 1. The numbers of genes with a given bias are visualized in the density plot in the lower part of the figure; dark gray denotes intermediate sex-biased expression
Image Credit: Cheng et al., 2016

Kirkpatrick says “In the last few years, human genetics has been revolutionized by the discovery of evidence for widespread and recent adaptive evolution across the human genome. This study brings that picture into real time: we now see evidence for selection on many genes working within the lifetimes of living individuals. Further, the type of selection involves gene variants (alleles) that improve survival in one sex while decreasing it in the other. What is good genetically for females is bad for males, and vice versa.”

This work was supported by the Swiss National Science Foundation Grant CRSII3-147625 to MK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The authors have declared that no competing interests exist.

Article: Sex-Specific Selection and Sex-Biased Gene Expression in Humans and Flies, Cheng C, Kirkpatrick M, PLOS Genetics, doi:10.1371/journal.pgen.1006170, published 22 September 2016.

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