Macfarlane Catriona, Simmonds Peter
Center for Infectious Diseases, University of Edinburgh, Summerhall, Edinburgh, Scotland EH9 1QH, UK.
J Mol Evol. 2004 Nov;59(5):642-56. doi: 10.1007/s00239-004-2656-1.
Human endogenous retroviruses (HERVs) are the remnants of ancient germ cell infection by exogenous retroviruses and occupy up to 8% of the human genome. It has been suggested that HERV sequences have contributed to primate evolution by regulating the expression of cellular genes and mediating chromosome rearrangements. After integration approximately 28 million years ago, members of the HERV-K (HML-2) family have continued to amplify and recombine. To investigate the utility of HML-2 polymorphisms as markers for the study of more recent human evolution, we compiled a list of the structure and integration sites of sequences that are unique to humans and screened each insertion for polymorphism within the human genome databases. Of the total of 74 HML-2 sequences, 18 corresponded to complete or near-complete proviruses, 49 were solitary long terminal repeats (LTRs), 6 were incomplete LTRs, and 1 was a SVA retrotransposon. A number of different allelic configurations were identified including the alternation of a provirus and solitary LTR. We developed polymerase chain reaction-based assays for seven HML-2 loci and screened 109 human DNA samples from Africa, Europe, Asia, and Southeast Asia. Our results indicate that the diversity of HML-2 elements is higher in African than non-African populations, with population differentiation values ranging from 0.6 to 9.8%. These findings denote a recent expansion from Africa. We compare the phylogenetic relationships of HML-2 sequences that are unique to humans and consider whether these elements have played a role in the remodeling of the hominid genome.
人类内源性逆转录病毒(HERVs)是外源性逆转录病毒对古代生殖细胞感染的残余物,占据人类基因组的比例高达8%。有人提出,HERV序列通过调节细胞基因表达和介导染色体重排,对灵长类动物的进化做出了贡献。在大约2800万年前整合之后,HERV-K(HML-2)家族的成员持续进行扩增和重组。为了研究HML-2多态性作为研究更近人类进化标记的效用,我们编制了一份人类特有序列的结构和整合位点清单,并在人类基因组数据库中筛选每个插入片段的多态性。在总共74个HML-2序列中,18个对应完整或近乎完整的前病毒,49个是单独的长末端重复序列(LTRs),6个是不完整的LTRs,1个是SVA逆转座子。鉴定出了许多不同的等位基因构型,包括前病毒和单独LTR的交替。我们针对7个HML-2基因座开发了基于聚合酶链反应的检测方法,并对来自非洲、欧洲、亚洲和东南亚的109份人类DNA样本进行了筛选。我们的结果表明,非洲人群中HML-2元件的多样性高于非非洲人群,群体分化值在0.6%至9.8%之间。这些发现表明最近有从非洲扩张的情况。我们比较了人类特有的HML-2序列的系统发育关系,并考虑这些元件是否在原始人类基因组的重塑中发挥了作用。