Evolutionarily Diverged Regulation of X-chromosomal Genes as a Primal Event in Mouse Reproductive Isolation

Improper gene regulation is implicated in reproductive isolation,but its genetic and molecular bases are unknown. we previously reported that a mouse inter-subspecific x chromosome substitution strain shows reproductive isolation characterized by male-specific sterility due to disruption of meiotic entry in spermatogenesis. here,we conducted comprehensive transcriptional profiling of the testicular cells of this strain by microarray. the results clearly revealed gross misregulation of gene expression in the substituted donor x chromosome. such misregulation occurred prior to detectable spermatogenetic impairment,suggesting that it is a primal event in reproductive isolation. the misregulation of x-linked genes showed asymmetry; more genes were disproportionally downregulated rather than upregulated. furthermore,this misregulation subsequently resulted in perturbation of global transcriptional regulation of autosomal genes,probably by cascading deleterious effects. remarkably,this transcriptional misregulation was substantially restored by introduction of chromosome 1 from the same donor strain as the x chromosome. this finding implies that one of regulatory genes acting in trans for x-linked target genes is located on chromosome 1. this study collectively suggests that regulatory incompatibility is a major cause of reproductive isolation in the x chromosome substitution strain. © 2014 oka et al.