人类内源性逆转录病毒HERV-K14家族:其他细胞序列的状态、变体、进化及动员

Human endogenous retrovirus HERV-K14 families: status, variants, evolution, and mobilization of other cellular sequences.

作者信息

Flockerzi Aline, Burkhardt Stefan, Schempp Werner, Meese Eckart, Mayer Jens

机构信息

Department of Human Genetics, Building 60, University of Saarland, 66421 Homburg, Germany.

出版信息

J Virol. 2005 Mar;79(5):2941-9. doi: 10.1128/JVI.79.5.2941-2949.2005.

Abstract

The human genome harbors many distinct families of human endogenous retroviruses (HERVs) that stem from exogenous retroviruses that infected the germ line millions of years ago. Many HERV families remain to be investigated. We report in the present study the detailed characterization of the HERV-K14I and HERV-K14CI families as they are represented in the human genome. Most of the 68 HERV-K14I and 23 HERV-K14CI proviruses are severely mutated, frequently displaying uniform deletions of retroviral genes and long terminal repeats (LTRs). Both HERV families entered the germ line approximately 39 million years ago, as evidenced by homologous sequences in hominoids and Old World primates and calculation of evolutionary ages based on a molecular clock. Proviruses of both families were formed during a brief period. A majority of HERV-K14CI proviruses on the Y chromosome mimic a higher evolutionary age, showing that LTR-LTR divergence data can indicate false ages. Fully translatable consensus sequences encoding major retroviral proteins were generated. Most HERV-K14I loci lack an env gene and are structurally reminiscent of LTR retrotransposons. A minority of HERV-K14I variants display an env gene. HERV-K14I proviruses are associated with three distinct LTR families, while HERV-K14CI is associated with a single LTR family. Hybrid proviruses consisting of HERV-K14I and HERV-W sequences that appear to have produced provirus progeny in the genome were detected. Several HERV-K14I proviruses harbor TRPC6 mRNA portions, exemplifying mobilization of cellular transcripts by HERVs. Our analysis contributes essential information on two more HERV families and on the biology of HERV sequences in general.

摘要

人类基因组中存在许多不同的人类内源性逆转录病毒(HERV)家族,这些家族起源于数百万年前感染种系的外源性逆转录病毒。许多HERV家族仍有待研究。我们在本研究中报告了HERV-K14I和HERV-K14CI家族在人类基因组中的详细特征。68个HERV-K14I和23个HERV-K14CI前病毒大多发生了严重突变,经常出现逆转录病毒基因和长末端重复序列(LTR)的一致缺失。这两个HERV家族大约在3900万年前进入种系,这一点在类人猿和旧世界灵长类动物中的同源序列以及基于分子钟计算的进化年龄中得到了证明。这两个家族的前病毒都是在一段短暂的时期内形成的。Y染色体上的大多数HERV-K14CI前病毒模拟了更高的进化年龄,表明LTR-LTR分歧数据可能会显示错误的年龄。生成了编码主要逆转录病毒蛋白的完全可翻译的共有序列。大多数HERV-K14I基因座缺乏env基因,在结构上让人联想到LTR逆转座子。少数HERV-K14I变体显示有env基因。HERV-K14I前病毒与三个不同的LTR家族相关,而HERV-K14CI与一个单一的LTR家族相关。检测到由HERV-K14I和HERV-W序列组成的杂交前病毒,这些序列似乎在基因组中产生了前病毒后代。几个HERV-K14I前病毒含有TRPC6 mRNA部分,例证了HERV对细胞转录本的动员作用。我们的分析为另外两个HERV家族以及一般HERV序列的生物学提供了重要信息。

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