Evolution of T-cell Receptor Gamma and Delta Constant Region and Other T-Cell-Related Proteins in the Human-Rodent-Artiodactyl Triplet

In this paper we report a detailed comparative and evolutionary analysis of the sequences of constant T-cell receptor (Tcr) Cγδ genes of artiodactyls compared to the homologous sequences of rodents and primates. Because of the frequency and physiological distribution of γδ T-cells in different animals, rodents and humans are defined as “γδ low” species and ruminants as “γδ high” species. Such a characteristic seems to be due to an adaptive role of γδ T-cell function. By analyzing the ruminant gene phylogeny of Tcr Cγ we were able to estimate the distance between cattle and sheep at 18 million years ago, a time that is in agreement with other nonmolecular estimates. For Tcr Cγδ genes a peculiar phylogenetic relationship was found, with human and mouse clustering together and leaving artiodactyls apart. By using appropriate outgroups, the same phylogenetic pattern was obtained with other T-cell related sequences: namely, Tcr Cα chain, CD3 γ and δ invariant subunits, Interleukin-2, Interleukin-2 receptor α chain and Interleukin-1β with the exception of Tcr Cβ chain and Interleukin-1α. In contrast, the analysis of all other T-cell nonrelated genes available in primary databases reveals a different tree, where primates and artiodactyls are sister taxa and rodents are apart in accordance with the current view of mammalian phylogeny. These data are relevant to important evolutionary issues. They show how misleading a phylogeny based on a single or on a few homologous genes may be. In addition they demonstrate that genes with correlated functions may evolve in a lineage specific manner probably in relation to environmental conditions.