Rapid evolution of the embryonically-expressed homeobox gene LEUTX within primates

LEUTX is a homeodomain transcription factor expressed in the very early embryo with a function around embryonic genome activation. The LEUTX gene is found only in eutherian mammals, including humans, but unlike the majority of homeobox genes, the encoded amino acid sequence is very different between divergent mammalian species. However, whether dynamic evolution has also occurred between closely related mammalian species remains unclear. In this work, we perform a comparative genomics study of LEUTX within the primates, revealing dramatic evolutionary sequence change between closely related species. Positive selection has acted on sites in the LEUTX protein, including six sites within the homeodomain; this suggests that selection may have driven changes in the set of downstream targets. Transfection into cell culture followed by transcriptomic analysis reveals small functional differences between human and marmoset LEUTX, suggesting rapid sequence evolution has fine-tuned the role of this homeodomain protein within the primates. SignificanceHomeobox genes are key regulators of animal development and are therefore often highly conserved between divergent species. However, recent work has uncovered several apparently fast-evolving homeobox genes expressed during mammalian development, one of which is LEUTX. Here we show that the LEUTX genes of primates are highly variable, and that these sequence changes have resulted in small modifications to its protein function. This continued rapid divergence of an embryonic gene between closely related species is significant to the areas of evolutionary, developmental and genome biology.