Human-specific integrations of the HERV-K endogenous retrovirus family
Human-specific integrations of the HERV-K endogenous retrovirus family
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DOI：
10.1128/jvi.72.12.9782-9787.1998
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发表时间：
1998-12-01
影响因子：
5.4
通讯作者：
Mager, DL
中科院分区：
文献类型：
--
作者：
Medstrand, P;Mager, DL
人类和其他灵长类动物的基因组中存在几个不同的内源性逆转录病毒样序列（HERV）家族。这些家族之一，HERV-K 家族，包含编码功能蛋白的成员，并且与胰岛素依赖型糖尿病 (IDDM) 的病因学有关。由于潜在的功能和疾病相关性，确定个体之间是否存在 HERV-K 相关的遗传差异非常重要。在这项研究中，我们研究了 HERV-K 长末端重复序列 (LTR) 的分歧和进化年龄，主要取自 GenBank 中的随机人类克隆的 37 个 LTR 被比对并分为九个簇，序列分歧逐渐减小。簇 1 序列平均有 8.6% 的差异，而簇 9 LTR（以完全测序的 HERV-K10 克隆的 LTR 为代表）之间的平均差异仅为 1.1%。然后通过基因组 PCR 研究来自不同簇的 18 个 LTR 的进化年龄，以确定不同灵长类物种中是否存在逆转录病毒元件。在猴子和猿中检测到来自较高分歧簇的 LTR，而来自较低分歧簇的 LTR 是在进化后期获得的。值得注意的是，第 9 簇的 LTR 仅在人类的所有 9 个检查基因座中被发现。使用针对簇 9 LTR 的寡核苷酸探针进行的基因组 Southern 分析表明，具有此类 LTR 的 HERV-K 元件在人类和类人猿的基因组中独立扩增。这是人类特异性内源性逆转录病毒整合的第一份报告，并表明一些 HERV 的扩增时间比之前认为的要晚得多。这些元件可能仍然活跃地转座，因此可能代表与疾病发展相关的遗传变异的来源。
Several distinct families of endogenous retrovirus-like sequences (HERVs) exist in the genomes of humans and other primates. One of these families, the HERV-K group, contains members that encode functional proteins and that have been implicated in the etiology of insulin-dependent diabetes mellitus (IDDM), Because of potential functional and disease relevance, it is important to determine if there are HERV-K-associated genetic differences between individuals. In this study, we have investigated the divergence and evolutionary age of HERV-K long terminal repeats (LTRs), Thirty-seven LTRs, taken Primarily from random human clones in GenBank, were aligned and grouped into nine clusters with decreasing sequence divergence. Cluster 1 sequences are 8.6% divergent, on average, whereas cluster 9 LTRs, represented by the LTRs of the fully sequenced HERV-K10 clone, show an average of only 1.1% divergence from each other, The evolutionary age of 18 LTRs from different clusters was then investigated by genomic PCR to determine presence or absence of the retroviral element in different primate species. LTRs from clusters of higher divergence were detected in monkeys and apes, whereas LTRs in clusters with lower divergence were acquired later in evolution. Notably, LTRs of cluster 9 were found only in humans at all nine loci examined. Genomic Southern analysis with an oligonucleotide probe specific for cluster 9 LTRs suggests that HERV-K elements with this type of LTR expanded independently in the genomes of humans and the great apes, This is the first report of endogenous retroviral integrations that are specific to humans and indicates that some HERVs have amplified much later than previously thought. These elements may still be actively transposing and may therefore represent a source of genetic variation linked to disease development.