Insights into the Evolutionary History of the X-Linked Sex Reversal Mutation in Mus minutoides: Clues from Sequence Analyses of the Y-Linked Sry Gene

Abstract

The African pygmy mouse, Mus minutoides, is one of the very few mammal species that deviates from the classical mammalian XX/XY sex chromosome system by presenting a high proportion of fully fertile sex-reversed females. Since the still unknown sex reversal mutation is X-linked (X*), they are designated as X*Y females. Until now, X*Y females had only been identified in Southern Africa, but data were lacking for the rest of the vast sub-Saharan distribution range of this species. In this study, the PCR genotyping of the Y-linked Sry gene on 72 females from Western Africa (Guinea, Ivory Coast and Ghana) uncovered 10 sex-reversed females distributed in the 3 countries. This expands our understanding of the geographical distribution and temporal origin (dated at 0.9 mya) of the sex reversal mutation. In addition, we sequenced and analyzed a fragment of the Sry gene (including the complete high-mobility group, i.e. HMG box, and the partial C-terminal region). The results demonstrate the presence of multiple polymorphic copies of the gene as reported in other rodent species and reveal, more unexpectedly, an extremely high proportion of amino acid replacement within the HMG box. In effect, the predicted HMG box protein sequence similarity between some populations of M. minutoides is as low as 94.9%, and at the interspecific level (within genus), it drops to only 91.1% between M. minutoides and M. musculus.