Post-genomics toward understanding of mutually sustainable biodiversity

我们在以下案例中调查并获得了关于基因表达改变或丢失的显著结果。这些结果证实了我们的假设，即人类的进化不是通过获得新的基因，而是通过改变基因组中现有基因的表达或丢失来实现的。(1)尿酸氧化酶基因(UOX)：UOX是一个单拷贝基因，其产物在嘌呤代谢中起着重要作用。然而，该基因在导致大猩猩和小猩猩独立进化的干细胞谱系中已经变得不起作用。这些独立的非功能化被发现是由于灵长类UOX经常使用CAG密码子，而CAG密码子容易出现终止密码子。还发现，在UOX恶化之前，编码产生UOX底物的酶的XOR的表达已经被抑制。因此，我们提供了一个涉及代谢途径的分子协同进化的实例。(2)唾液酸羟基酶基因：唾液酸羟基酶是人类sp…中的一种。更多特定的假基因。由于Alu插入介导的外显子缺失，该基因成为假基因。据估计，这一缺失发生在大约300万年前，就在人类头骨容量开始扩大之前。因此推测，基因缺失可能在人类进化过程中发挥了重要作用。我们还进行了CMAH单倍型的群体调查。系统地理分析表明，早在现代人组织之前，非洲就存在着强大的种群结构。(3)性染色体的分化：我们从人类基因组分析中证明，Y染色体上男性决定基因的存在和位置是哺乳动物性染色体通过抑制重组而逐步分化的原因。我们认为，阻止性染色体之间的重组允许有害突变在Y染色体上积累，这是Y染色体上基因不断退化和丢失的原因。(4)主要组织相容性复合体(MHC)I类基因：我们研究了新大陆猴子的MHC I类基因。与人类I类基因的比较表明，新大陆猴子分享了大部分I类基因，而猴灵长类动物I类基因随后的进化主要是由现有基因的丢失决定的。我们还认为，功能I类基因座的数量受到自然选择的很好的调节，反映了I类分子的双重功能，T细胞限制胸腺和入侵病原体的加工肽的呈递。较少

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 … More 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