Widespread male-female expression imbalance of X-linked genes across phrynosomatid lizards

Abstract

Classic theory on sex chromosome evolution predicts that selection should restore ancestral diploid expression for hemizygous X-linked genes in males. However, this dosage compensation is often incomplete, leaving X enriched for genes with female-biased expression. In this context, iguanian lizards are noteworthy among vertebrates because several species from separate families appear to exhibit both near-complete dosage compensation and male-female expression balance across their ancient, homologous X chromosomes. We tested for this pattern in a phrynosomatid iguanian, Sceloporus undulatus (Eastern Fence Lizard), and instead found that both ancient and more recently sex-linked regions of the X chromosome are enriched for genes with female-biased expression, regardless of age (neonate, maturing, adult) or tissue (brain, liver, muscle). By expanding our analysis across 10 phrynosomatid species spanning 4 genera, we found that male-female expression imbalance on the ancestral region of X is phylogenetically conserved. We also found that an inferred chromosomal rearrangement in the S. jarrovii lineage has resulted in the novel acquisition of female-biased expression by a formerly autosomal region. Whereas sex-biased expression of the ancestral region of X is primarily due to females overexpressing X-linked genes relative to autosomal genes, sex-biased expression of these formerly autosomal genes in S. jarrovii is primarily due to males underexpressing this putative neo-X region. We conclude that male-female expression imbalance on X is widespread across phrynosomatids, potentially reflecting both overexpression in females for ancestral regions that have evolved dosage compensation and underexpression in males for neo-X regions in which dosage compensation has yet to evolve.