SummaryIn multicellular organisms, telomerase is required to maintain telomere length in the germline but is dispensable in the soma. Mice, for example, express telomerase in somatic and germline tissues, while humans express telomerase almost exclusively in the germline. As a result, when telomeres of human somatic cells reach a critical length the cells enter irreversible growth arrest called replicative senescence. Replicative senescence is believed to be an anticancer mechanism that limits cell proliferation. The difference between mice and humans led to the hypothesis that repression of telomerase in somatic cells has evolved as a tumor-suppressor adaptation in large, long-lived organisms. We tested whether regulation of telomerase activity coevolves with lifespan and body mass using comparative analysis of 15 rodent species with highly diverse lifespans and body masses. Here we show that telomerase activity does not coevolve with lifespan but instead coevolves with body mass: larger rodents repress telomerase activity in somatic cells. These results suggest that large body mass presents a greater risk of cancer than long lifespan, and large animals evolve repression of telomerase activity to mitigate that risk.
HLA class-II proteins are cell-surface molecules that present antigens to T cells, and their expressional regulation is crucial to the immune reaction. Sequence variation at the regulatory region can directly affect the gene expression level. We cloned and sequenced a 4.7-kb region containing the regulatory region, exon1, and partial intron1 of both HLA-DPA1 and DPB1 genes in 25 variable sequences from southern Chinese ethnic groups and got a high-density map of 162 single nucleotide polymorphisms (SNPs): seven in 5¢-flanking regions, four in 5¢-untranslated regions, and four in the coding regions. By comparing these data with SNPs in dbSNP database in the NCBI, 145 SNPs (89.5%) were novel. In addition, eight genetic variations of insertion-deletion polymorphisms (INDELs) were discovered within the 4.7-kb region. These high-resolution maps can be used as resources of markers for association studies of complex diseases, assessment of individuals' predisposition to diseases, and tailoring of therapies, as well as research markers for population genetics and evolution.
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