| Research Abstract |
We have investigated and obtained significant results with respect to altered expression or loss of genes in the following cases. These results substantiate our hypothesis that the human has evolved not by gain of new genes, but by altered expression or loss of existing genes in the genome.
(1)Urate oxidase gene (UOX) : UOX is a single copy gene and the product plays an important role in the purine metabolism. However, the gene has become nonfunctional in the stem lineage leading to Great Apes and to Lesser Apse independently. These independent nonfunctionalizations are found to result from the fact that the primate UOX frequently uses a codon of CAG which is prone to a stop-codon. It is also found that, prior to the deterioration of UOX, the expression of XOR that encodes the enzyme producing a substrate for UOX has been suppressed. Thus we have provided an instance of molecular coevolution involved in a metabolic pathway.
(2)Sialic acid hydroxylase (CMAH) gene : CMAH is one of human sp
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ecific pseudogenes. It became a psuedogene owing to an exon deletion mediated through an Alu insertion. This deletion is estimated to be about 3 million years ago, just before the human cranium capacity began to expand. It is therefore speculated that loss of gene might have played important roles in human evolution. We have also carried out population surveys of CMAH haplotypes. The phylogeographic analysis suggests strong population structure within Africa well before modem humans orginated.
(3)Differentiation of sex chromosomes : We have demonstrated from the human genome analysis that the existence and location of male-determining genes on the Y-chromosome has been responsible for the step-wise differentiation of mammalian sex chromosomes by suppression of recombination. We have argued that prevention of recombination between sex chromosomes has allowed for deleterious mutations to accumulate on the Y chromosome and that this accounts for constant deterioration and loss of genes on the Y chromosome.
(4)Major histocompatibility complex (MHC) class I gene : We have studied MHC class I genes in New World monkeys. The comparison with human class I genes showed that most of them are shared by New World monkeys and that the subsequent evolution of class I genes in simian primates has been shaped mainly by loss of existing genes. We also argued that the number of functional class I loci has been well regulated by natural selection reflecting the dual function of class I molecules, T cell restriction the thymus and presentation of processed peptides of invading pathogens. Less
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