RACE-SPECIFIC DISTRIBUTION OF THE TRPM8 GENE VARIANTS: SIGNS OF SELECTION
Race-Specific Distribution of the TRPM8 Gene Variants: Signs of Selection
Voevoda M.I.,1,2,3 Potapova T.A.,1 Romashchenko A.G.,1 Yudin N.S.,1,2,3 Babenko V.N.,1 Pilipenko I.V.1 Kobzev V.F.,1 Maksimov V.N.,2 Rogaev E.I.1,4,5,6
1Center for Brain Neurobiology and Neurogenetics, The Federal Research Center Institute of Cytology and Genetics the Siberian Branch of the Russian Academy of Sciences, Russia; 2Federal State Budgetary of Scientific Institution «Institution of Internal and Preventive Medicine», Russia; 3Novosibirsk State University, Russia; 4Lomonosov Moscow State University, Russia; 5Vavilov Institute of General Genetics, Russia; 6BNRI, Department of Psychiatry, University of Massachusetts Medical School, USA
A frequency distribution of the haplotypes at six SNPs in the TRPM8 gene sequences in Eurasia human populations, including Russians, Altai Kazakhs and Tundra Chukchi has been studied. Four of six SNPs are in exon 7 and one disposes in exon 11. Both exons encode TRPM8 NH2 domain fragments. The sixth SNP is localized in exon 23, encoding COOH domain fragment. The Chukchi and Russians display the most pronounced differences in pattern of diversity and frequencies of the some haplotypes. The main difference between the haplotype variants is determined by the SNP of exon 11, which gives the substitution Ser/Asn in the protein. The frequency of the overrepresentative Ser haplotype (H1) differ in the examined populations, amounting to 72% in Russians, 42.9% in Kazakhs and 24.6% in Chukchi. The Asn haplotypes carrying additionally the minor alleles at synonymous SNPs of exon 7 are characteristic for Asian populations: they spread with a total frequency about 31.2% in the Chukchi versus 10.2% in the Kazakhs and only 2,4% in the Russians. The frequency of all Asn haplotypes in the Africans is comparable to Chukchi; however, they have lesser 10% of the synonymous SNPs of exon 7. Molecular analysis of the six TRPM8 mRNA isoforms has shown that they are transcribed from the TRPM8 gene H1 variant but have the different translation initiation sites which are generated by alternative splicing from TRPM8 pro-mRNA.
It is possible to assume that the prevalent fixation of the haplotypes with minor alleles of exon 7 in Asians is a Eurasian acquisition, which is more characteristic of the Eastern Asians as compared with the Western Asians. The separation of the European branch of the anatomically modern man out of Africa with a relatively low haplotype diversity at the TRPM8 gene (mainly, with H1 haplotype) was likely started in the Mesolithic and was fixed later.