Evolutionarily diverged regulation of X-chromosomal genes as a primal event in mouse reproductive isolation.

Ayako Oka,Hironori Fujisawa,Toyoyuki Takada,Toshihiko Shiroishi

doi:10.1371/journal.pgen.1004301

Abstract

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.

Highlights

Reproductive isolation is a typical consequence of deleterious epistatic interactions between genes that have evolutionarily diverged in species or subspecies [1,2,3]
Using hybrid animals between two mouse subspecies, Goncalves et al [5] reported that the expression of approximately 30% of non-imprinted autosomal genes expressed in the liver is diverged by variants in cis-regulatory elements and variants in regulatory factors acting in trans
Reproductive isolation characterized by male sterility and decreased viability is important for speciation, because it suppresses free genetic exchange between two diverged populations and accelerates the genetic divergence

Summary

Introduction

Reproductive isolation is a typical consequence of deleterious epistatic interactions between genes that have evolutionarily diverged in species or subspecies [1,2,3]. A confounding factor that makes it difficult to identify sterilitycausing genes is that these genes function properly in their parental pure species (or subspecies), and deleterious interactions (i.e., genetic incompatibility) between them only occur in the hybrid genetic background [4]. Using hybrid animals between two mouse subspecies, Goncalves et al [5] reported that the expression of approximately 30% of non-imprinted autosomal genes expressed in the liver is diverged by variants in cis-regulatory elements and variants in regulatory factors acting in trans. The rates of variants in cis-regulatory elements is higher than those in regulatory factors acting in trans. Such evolutionary divergence in transcriptional regulation may contribute to phenotypic differences and genetic incompatibilities underlying reproductive isolation

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Discussion

Conclusion