Genetics, Vol. 167, 879-888, June 2004, Copyright © 2004
doi:10.1534/genetics.103.025072

Rapid Evolution of Mammalian X-Linked Testis-Expressed Homeobox Genes

Xiaoxia Wang and Jianzhi Zhang¹

Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan 48109

¹ Corresponding author: Department of Ecology and Evolutionary Biology, University of Michigan, 3003 Nat. Sci. Bldg., 830 N. University Ave., Ann Arbor, MI 48109.
E-mail: jianzhi{at}umich.edu

Homeobox genes encode transcription factors that function in various developmental processes and are usually evolutionarily conserved in their sequences. However, two X-chromosome-linked testis-expressed homeobox genes, one from rodents and the other from fruit flies, are known to evolve rapidly under positive Darwinian selection. Here we report yet another case, from primates. TGIFLX is an X-linked homeobox gene that originated by retroposition of the autosomal gene TGIF2, most likely in a common ancestor of rodents and primates. While TGIF2 is ubiquitously expressed, TGIFLX is exclusively expressed in adult testis. A comparison of the TGIFLX sequences among 16 anthropoid primates revealed a significantly higher rate of nonsynonymous nucleotide substitution (d_N) than synonymous substitution (d_S), strongly suggesting the action of positive selection. Although the high d_N/d_S ratio is most evident outside the homeobox, the homeobox has a d_N/d_S of 0.89 and includes two codons that are likely under selection. Furthermore, the rate of radical amino acid substitutions that alter amino acid charge is significantly greater than that of conservative substitutions, suggesting that the selection promotes diversity of the protein charge profile. More interestingly, an analysis of 64 orthologous homeobox genes from humans and mice shows substantially higher rates of amino acid substitution in X-linked testis-expressed genes than in other genes. These results suggest a general pattern of rapid evolution of mammalian X-linked testis-expressed homeobox genes. Although the physiological function of and the exact selective agent on TGIFLX and other rapidly evolving homeobox genes are unclear, the common expression pattern of these transcription factor genes led us to conjecture that the selection is related to one or more aspects of male reproduction and may contribute to speciation.

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