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 the X chromosome 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 similar expression balance 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 ten phrynosomatid species spanning four genera, we found that male–female expression imbalance on the ancestral region of X is phylogenetically conserved in this family. We also found that an inferred chromosomal rearrangement in Sceloporus jarrovii has resulted in the evolution 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 genes in 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.