Molecular evolution of PKD2 gene family in mammals
PKD2 gene encodes a critical cation channel protein that plays important roles in various developmental processes and is usually evolutionarily conserved. In the present study, we analyzed the evolutionary patterns of PKD2 and its homologous genes (PKD2L1, PKD2L2) from nine mammalian species. In this study, we demonstrated the orthologs of PKD2 gene family evolved under a dominant purifying selection force. Our results in combination with the reported evidences from functional researches suggested the entire PKD2 gene family are conserved and perform essential biological roles during mammalian evolution. In rodents, PKD2 gene family members appeared to have evolved more rapidly than other mammalian lineages, probably resulting from relaxation of purifying selection. However, positive selection imposed on synonymous sites also potentially contributed to this case. For the paralogs, our results implied that PKD2L2 genes evolved under a weaker purifying selection constraint than PKD2 and PKD2L1 genes. Interestingly, some loop regions of transmembrane domain of PKD2L2 exhibited higher P N/P S ratios than expected, suggesting these regions are more functional divergent in organisms and worthy of special attention.
KeywordsPKD2 gene family Mammalian Evolutionary patterns Rodents
This work was supported by a grant of the National Key Basic Research Program of China to Prof. Qin Zhou (2005CB522506) and a grant of the National Key Basic Research Program of China to academician Yuquan Wei (2004CB518800). The work was also supported by a grant of the S&T Bureau of Sichuan Province to Qin Zhou.
- Gonzalez-Perrett S, Kim K, Ibarra C, Damiano AE, Zotta E, Batelli M, Harris PC, Reisin IL, Arnaout MA, Cantiello HF (2001) Polycystin-2, the protein mutated in autosomal dominant polycystic kidney disease (ADPKD), is a Ca2+-permeable nonselective cation channel. Proc Natl Acad Sci USA 98:1182–1187. doi: 10.1073/pnas.021456598 PubMedCrossRefGoogle Scholar
- Hateboer N, Veldhuisen B, Peters D, Breuning MH, San-Millan JL, Bogdanova N, Coto E, van Dijk MA, Afzal AR, Jeffery S, Saggar-Malik AK, Torra R, Dimitrakov D, Martinez I, de Castro SS, Krawczak M, Ravine D (2000) Location of mutations within the PKD2 gene influences clinical outcome. Kidney Int 57:1444–1451. doi: 10.1046/j.1523-1755.2000.00989.x PubMedCrossRefGoogle Scholar
- Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B, Saris JJ, Reynolds DM, Cai Y, Gabow PA, Pierides A, Kimberling WJ, Breuning MH, Deltas CC, Peters DJ, Somlo S (1996) PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272:1339–1342. doi: 10.1126/science.272.5266.1339 PubMedCrossRefGoogle Scholar
- Wu G, Markowitz GS, Li L, D’Agati VD, Factor SM, Geng L, Tibara S, Tuchman J, Cai Y, Park JH, van Adelsberg J, Hou H Jr, Kucherlapati R, Edelmann W, Somlo S (2000) Cardiac defects and renal failure in mice with targeted mutations in PKD2. Nat Genet 24:75–78. doi: 10.1038/71724 PubMedCrossRefGoogle Scholar