Fast evolutionary turnover and overlapping variances of sex-biased gene expression patterns defy a simple binary classification of sexes

Abstract

Abstract The phenotypic differences between the sexes are generated by genes with sex-biased expression. These range from a few major regulators to large numbers of organ-specific effector genes in sexually mature individuals. We explore the variation and evolutionary patterns of these genes in a large dataset from natural populations of sub-species and species of mice across an evolutionary distance of two million years. Within these short phylogenetic distances, we find a faster evolutionary turnover of sex-biased gene expression compared to non-sex-biased genes and a faster adaptive protein evolution for the genes that are sex-biased in a given taxon. We show that sex-biased genes occur only in a subset of the co-expression modules of each organ and the turnover of genes between the taxa occurs often within the main modules. Given that our dataset is the first in animals that was generated in a combined population genetic and phylogenetic context, we were interested to study the within-group variances for sex-biased gene expression in somatic and gonadal tissues and their evolutionary turnover. To visualize the individual variances, we have developed a sex-biased gene expression index (SBI) that represents the cumulative expression of all sex-biased genes for each individual in each organ. We find that SBI distributions can range from close to binary patterns to overlapping patterns between the sexes. They do not correlate between organs of the same individuals, thus supporting a mosaic model of sex-determination of individuals. Comparison with data from humans shows fewer sex-biased genes compared to mice and strongly overlapping SBI distributions between the sexes. We conclude that sex-biased genes are subject to fast evolution, with no long-term stability for male or female expression characteristics.