Evolution Study On Part Of Positve-Selection Genes Expressed In Primate Btain And Evolutionary Analysis On TTL.6 Gene

Base on Darwinian evolution theory and rencent molecular evolution theory, positive selection may contribute to human brain evolution, and such progress may embed some impression on gene or genomic substitution pattern. In our former study, we cataloged genes expressed in human brain (about 10,000 gnes), and sequenced the orthologous sequence of these genes in chimpazee. In this study, we selected 16 of these positive-selection genes and then using PCR and Sequencing technique we acquired orthologous sequence in another two representative primates: white-brown ape and macaca, and then took further evolutionary analysis. Among these 16 positive selected genes we further analysised a tubulin ligase family member TTL.6 gene. This gene is primarily expressed in testis except for brain. We sequenced samples from chimpanzee,gorilla,orangutan,while-brown gibbon,maca and human samples from Asian,African,Europe and Melanecian. Sequence data included coding region (1710bps) and noncoding region (289bps). Base on phylogenetic relationship among these primates construced by Goodman (1998), we conducted phylogenetic-based evolution rate analysis,positive selection sites analysis,allele frequency distribution among human population and neutrality test. Our results are listed as followed. 1. Some of these 16 genes are pseudogene in certain lineages. This is caused by insert/delete (in/del) mutation that contributed shift frame, or nonsense mutation that produce unmature protein. 2. Ka/Ks is significantly greater than 1 in human and chimpanzee, this is signal of positive selection in human or chimpanzee lineage. Variable evolution rate was also detected on other lineage because of variable selection pressure, since Ka/Ks is significantly smaller or greater than 1, or can not reject hypothesis that Ka/Ks equal to 1. 3. The sequence substitution patterns of TTL.6 in primates demonstrated a sharp difference in evolutionary rates among different primate lineages. Base on Z-test and Fisher's exact test, Ka/Ks is significantly greater than 1 in human, indicated accelerated evolution of TTL.6 in the human lineage, which was caused by Darwinian positive selection, was observed. While in other lineage such as less ape,macaca, it was negative selection caused slow evolution (Ka/Ks<1) worked. 4. Further analysis on sequence variations in human populations demonstrated an excess of derived common alleles, which was likely caused by genetic hitchhiking, also an implication of recent positive selection on TTL.6 in human populations. 5. Base on Yang's (2000) method we detected two human specific amino acid substitutions that were caused by Darwinian positive selection. Sliding-Window analysis also detected a region (800bp to 1300bp) own higher Ka/Ks ratio than other region. This region is concide with the two positive selected sites detected by Yang's (2000) method. These two substitution may contributed to adaptive evolution of this gene.