A Mouse Speciation Gene Encodes a Meiotic Histone H3 Methyltransferase

TLDR

Speciation genes restrict gene flow between incipient species and related taxa. The study identifies the mouse speciation gene Hst1 as Prdm9, a histone H3 lysine‑4 trimethyltransferase, and shows that introducing Prdm9 from a fertile allele rescues hybrid male infertility, restores normal chromatin organization, and implicates epigenetic regulation in hybrid sterility.

Abstract

Speciation genes restrict gene flow between the incipient species and related taxa. Three decades ago, we mapped a mammalian speciation gene, hybrid sterility 1 (Hst1), in the intersubspecific hybrids of house mouse. Here, we identify this gene as Prdm9, encoding a histone H3 lysine 4 trimethyltransferase. We rescued infertility in male hybrids with bacterial artificial chromosomes carrying Prdm9 from a strain with the "fertility" Hst1(f) allele. Sterile hybrids display down-regulated microrchidia 2B (Morc2b) and fail to compartmentalize gammaH2AX into the pachynema sex (XY) body. These defects, seen also in Prdm9-null mutants, are rescued by the Prdm9 transgene. Identification of a vertebrate hybrid sterility gene reveals a role for epigenetics in speciation and opens a window to a hybrid sterility gene network.