摘要
尿酸氧化酶(尿酸酶;EC1.7.3.3;UOX)是一种在嘌呤代谢途径中催化尿酸氧化生成尿囊素的酶。在灵长类动物漫长的进化过程中,人科动物尿酸氧化酶基因因突变失活,成为假基因。通过来源于10种不同生物尿酸氧化酶蛋白质序列比对,鉴别出发生在人科动物的共同祖先的尿酸氧化酶基因上的3个能够引起尿酸分解活性降低甚至丧失的初级突变位点以及发生在人尿酸氧化酶基因上的12个次级突变位点,同时运用定点突变技术对发生在人科动物共同祖先尿酸氧化酶基因上的初级突变位点进行了验证研究。根据这15个突变位点在人科动物尿酸氧化酶基因上出现的频率和灵长类动物的物种进化分支树,判断出上述突变位点在人尿酸氧化酶基因上发生的先后顺序,最终阐明了人尿酸氧化酶的进化轨迹。
Urate oxidase（ uricase; EC 1. 7. 3. 3; UOX） is an enzyme that catalyzes oxidation of uric acid to allantoin in purine metabolism. During the primate evolution,hominoids lose urate oxidase activity and become pseudogene. Protein sequence alignment of urate oxidases from 10 organisms enables the identification of 3 original mutations that could potentially diminish and abolish uricolytic activity in ancestors to hominoids and 12 secondary mutations in human. Rational site-directed mutagenesis led to the further identification of original mutations responsible for the inactivation of human urate oxidase. Based on to occurrence frequency of the15 mutations in hominid uric acid oxidase pseudogene and primate cladogram,we have determined the occurrence orders of these mutations on human urate oxidase pseudogene and illustrated the evolution trajectory of human urate oxidase.
出处
《药物生物技术》
CAS
2014年第4期287-292,共6页
Pharmaceutical Biotechnology
基金
国家自然科学基金(No.81072560)
关键词
人尿酸氧化酶
人科动物
假基因
初级突变
次级突变
猪尿酸氧化酶
定点突变技术
Human urate oxidase, Hominoids, Pseudogene, Original mutation, Secondary mutation, Porcine urate oxidase, Rationalsite-directed mutagenesis
