More than a hundred years ago Huxley and Darwin predicted the closest evolutionary relationship between humans and the African apes. Whereas the precise timing of the speciation events remains uncertain, there is a general agreement that Homo sapiens shared a common ancestor with Panpaniscwand (bonobo) and Pan troglodytes (chimpanzee) about 5-6 million years (Mya) ago. Compared with the billions of years of evolutionary history, 5-6 million years is just a short time. However, the hominoid evolution was at rapid pace and characterized by a dramatic increase in brain size and cognitive complexity, and eventually led to the emergence of our own species. What makes us different at the genetic level from other primates and particularly from our closest relatives, the great apes? This essential question in biology, with major consequences on our social life, ethical and philosophical perception of ourselves, has puzzled us for decades and yet attracted many geneticists and evolutionary biologists. DNA sequence comparison between human and chimpanzee revealed a strong similarity, up to nearly 99% in the gene coding region. We hypothesized that the differences in cognitive skills between primate species may be attributable to two primary aspects of genetic divergences, the sequence divergence of genes controlling the fine patterns of brain development and the differences in gene expression within the brain. Genetic differences may lie at different levels including gross alterations in cytogenetic architecture, local chromosomal rearrangements, gene family duplication, single gene modifications and differences in gene transcription and alternative splicing of mRNA. More than 55% of human genes are suggested alternatively spliced, which is one of the major mechanisms in generating protein diversity. Moreover, compared with other tissues and organs, the brain has the most number of genes with alternative splice forms. Using Polony (polymerase colony) technique, we intend to detect the difference of exon profile of brain-expressed genes between human and nonhuman primates, especially the human specific splice isoforms, which might be involved in the origin of human cognition. In addition, we aim to identify genes under strong Darwinian positive selection in the human lineage, which potentially contributed to the origin of humans. CXCRl is a G protein coupled receptor. We sequenced the complete coding region of the CXCRl gene in worldwide human populations and five representative nonhuman primate species. Our result indicated accelerated protein evolution in the human lineage, which was likely caused by Darwinian positive selection. The sliding window analysis and the codon-based neutrality test identified signatures of positive selection at the N-terminal ligand/receptor recognition domain of human CXCRl.
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