Positive selection in the evolution of mammalian interleukin-2 genes.


In vertebrates, there are many secreted regulatory proteins that participate in host defense. Interleukin-2 (IL-2) is one of these proteins, and it is secreted primarily by activated T lymphocytes. Interaction between IL-2 and its receptor on the T cell membrane triggers several signal transduction pathways, resulting in clonal expansion of T cells. While this proliferation-promoting activity is believed to be its main function, IL-2 can stimulate the functional differentiation of T cells as well. IL-2 is also known to be a proliferation and differentiation factor for a variety of cell types, such as B cells, natural killer cells, and myeloid cells (reviewed in Goldsmith and Greene 1994; Gaulton and Williamson 1994). Due to its ability to upregulate the immune system, IL2 has been widely used in immunotherapy for a number of diseases, including cancers and AIDS (e.g., Macey and Johnston 1990; Zou et al. 1999). IL-2 has also been of interest to evolutionists for testing the molecularclock hypothesis (Gillespie 1989; Ohta 1995). Here, we analyze the sequences available in GenBank and report detection of positive Darwinian selection in ancestral IL-2 genes of artiodactyls and discuss its implications. The IL-2 gene sequences of 15 mammalian species were obtained from GenBank (see fig. 1A for species names) and were aligned using CLUSTAL V (Higgins, Bleasby, and Fuchs 1992) with some visual adjustments. The number of codons in the alignment was 152 after the gaps were removed. (GenBank accession numbers and the alignment are available on request). We assumed that the phylogenetic tree of the species used was as that shown in figure 1A, which is generally accepted by molecular evolutionists (Hayasaka, Fujii, and Horai 1996 and references therein; de Jong 1998) and is also supported by the IL-2 gene. We first estimated the numbers of synonymous (dS) and nonsynonymous (dN) substitutions per site between 105 pairs of the 15 IL-2 sequences by the modified NeiGojobori method (Nei and Gojobori 1986; Zhang, Rosenberg, and Nei 1998) (table 1). The Jukes-Cantor corrected dS values were all smaller than 0.7, suggesting that there was no serious saturation of synonymous substitutions. This was particularly so for comparisons among the nonrodent species, for which the dS values were generally smaller than 0.2. It was observed that dN

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@article{Zhang2000PositiveSI, title={Positive selection in the evolution of mammalian interleukin-2 genes.}, author={Jason Y. Zhang and Masatoshi Nei}, journal={Molecular biology and evolution}, year={2000}, volume={17 9}, pages={1413-6} }