Duplication and positive selection among hominin-specific PRAME genes.
Duplication and positive selection among hominin-specific PRAME genes.
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DOI：
10.1186/1471-2164-6-120
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发表时间：
2005-09-13
期刊：
影响因子：
4.4
通讯作者：
Ponting C
中科院分区：
文献类型：
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作者：
Birtle Z;Goodstadt L;Ponting C
人类和黑猩猩之间的身体和表型差异在很大程度上是由我们的基因组差异指定的。染色体1的区域，它是人类之间的拷贝数多态性，其中至少包含32个亮度（优先表达）黑色素瘤）基因和假基因的抗原。
使用外显子和内含子的核替代率估计，我们表明，在过去的300万年中，有两个大的分段重复，分别是六个和七个人类启动基因。由于黑猩猩的分歧是我们发现的大约95-85万年前的易位在人类或小鼠的启发序列中，这些位点在预测的蛋白质结构的一个面上呈现出阳性选择的强烈证据。
我们预测，由于精子发生和卵子发生过程中快速分散的细胞之间的强烈竞争，普雷姆基因的演变为自适应。
The physiological and phenotypic differences between human and chimpanzee are largely specified by our genomic differences. We have been particularly interested in recent duplications in the human genome as examples of relatively large-scale changes to our genome. We performed an in-depth evolutionary analysis of a region of chromosome 1, which is copy number polymorphic among humans, and that contains at least 32 PRAME (Preferentially expressed antigen of melanoma) genes and pseudogenes. PRAME-like genes are expressed in the testis and in a large number of tumours, and are thought to possess roles in spermatogenesis and oogenesis. Using nucleotide substitution rate estimates for exons and introns, we show that two large segmental duplications, of six and seven human PRAME genes respectively, occurred in the last 3 million years. These duplicated genes are thus hominin-specific, having arisen in our genome since the divergence from chimpanzee. This cluster of PRAME genes appears to have arisen initially from a translocation approximately 95–85 million years ago. We identified multiple sites within human or mouse PRAME sequences which exhibit strong evidence of positive selection. These form a pronounced cluster on one face of the predicted PRAME protein structure. We predict that PRAME genes evolved adaptively due to strong competition between rapidly-dividing cells during spermatogenesis and oogenesis. We suggest that as PRAME gene copy number is polymorphic among individuals, positive selection of PRAME alleles may still prevail within the human population.