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Post-genomics toward understanding of mutually sustainable biodiversity

后基因组学有助于理解相互可持续的生物多样性

基本信息

批准号：
12304046
负责人：
TAKAHATA Naoyuki
金额：
$ 25.41万
依托单位：
The Graduate University for Advanced Studies (SOKENDAI)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2003
项目状态：
已结题

项目摘要

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

我们在以下情况下对基因表达改变或丢失进行了调查并获得了显着结果。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基因，而是通过改变基因组中现有基因的表达或丢失。（1）尿酸氧化酶基因（UOX）：UOX是单拷贝基因，其产物在嘌呤代谢中发挥重要作用。然而，该基因在独立导致大猿和小后殿的茎谱系中已失去功能。这些独立的非功能化被发现是由于灵长类 UOX 经常使用容易出现终止密码子的 CAG 密码子这一事实造成的。还发现，在UOX劣化之前，编码产生UOX底物的酶的XOR的表达已被抑制。因此，我们提供了参与代谢途径的分子协同进化的实例。(2)唾液酸羟化酶(CMAH)基因：CMAH是人类特异性假基因之一。由于 Alu 插入介导的外显子缺失，它变成了假基因。据估计，这种缺失发生在大约 300 万年前，就在人类颅骨容量开始扩大之前。因此推测基因的丢失可能在人类进化中发挥了重要作用。我们还开展了 CMAH 单倍型的人群调查。谱系地理学分析表明，早在现代人类出现之前，非洲就存在强大的人口结构。（3）性染色体的分化：我们从人类基因组分析中证明，Y染色体上雄性决定基因的存在和位置通过抑制重组导致了哺乳动物性染色体的逐步分化。我们认为，阻止性染色体之间的重组会导致有害突变在 Y 染色体上积累，从而导致 Y 染色体上的基因不断恶化和丢失。 (4) 主要组织相容性复合体 (MHC) I 类基因：我们研究了新世界猴的 MHC I 类基因。与人类 I 类基因的比较表明，其中大部分是新世界猴所共有的，并且猿猴灵长类 I 类基因的后续进化主要是通过现有基因的丢失而形成的。我们还认为，功能性 I 类基因座的数量受到自然选择的良好调节，反映了 I 类分子的双重功能、T 细胞限制胸腺和呈递入侵病原体的加工肽。较少的