Evolution of a hypervariable region of the low density lipoprotein receptor (LDLR) gene in humans and other hominoids.
Evolution of a hypervariable region of the low density lipoprotein receptor (LDLR) gene in humans and other hominoids.
复制标题
人类和其他类人猿低密度脂蛋白受体（LDLR）基因高变区的进化。
DOI：
10.1023/b:gene.0000040387.14317.98
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发表时间：
2004
期刊：
影响因子：
1.5
通讯作者：
Deininger,PrescottL
中科院分区：
文献类型：
--
作者：
Kass,DavidH;Knight,Alec;Deininger,PrescottL
灵长类动物中的重复序列已被证明以中性突变率进化，正如非编码常染色体基因座所预期的那样。然而，我们在低密度脂蛋白受体（LDLR）基因的3'非翻译区（UTR）内发现了具有高度加速进化速率的转录因子。在人类中，基于对8个不同种族背景的个体的序列分析，估计上游Alu（AluU）和下游Alu（AluD）的平均分歧分别增加了100倍和25倍。这些人都没有表现出相同的序列内的950个碱基的区域组成的这两个元件。核基因组中这一遗传区域的高变异性为人类人口研究、法医学和亲子鉴定提供了一个潜在的强大工具。此外，在非人类类人猿中，cDNAU的突变率也加快了，尽管程度较低，大约是其他类人猿元素的3倍。不同的Hominoidea物种的序列分析表明，它作为一个系统发育的工具。突变率高变的机制尚不清楚，但可能是由于人类谱系中的突变介导的基因转换而加速的。
Alurepeats in primates have been shown to evolve at a neutral mutation rate, as anticipated for non-coding autosomal loci. However, we have identifiedAluelements within the 3' untranslated region (UTR) of the low density lipoprotein receptor (LDLR) gene that exhibited highly accelerated rates of evolution. In humans, a 100- and 25-fold increase in average divergence, for an upstreamAlu(AluU) and a downstreamAlu(AluD) respectively, was estimated based on sequence analysis among eight individuals of diverse ethnic backgrounds. None of these individuals demonstrated identical sequences within a 950 base region consisting of these twoAluelements. The hypervariability of this genetic region in the nuclear genome yields a potentially powerful tool for human population studies, forensics and paternity. Additionally, the mutation rate ofAluU among non-human hominoids was also accelerated, although to a lesser extent of roughly 3-fold that of otherAluelements. Sequence analysis of various Hominoidea species demonstrated its utility as a phylogenetic tool. The mechanism for the hypervariability in mutation rates is unclear, but may be accelerated as a result ofAlu-mediated gene conversion in the human lineage.