High divergence in primate-specific duplicated regions:: Human and chimpanzee Chorionic Gonadotropin Beta genes
High divergence in primate-specific duplicated regions:: Human and chimpanzee Chorionic Gonadotropin Beta genes
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DOI：
10.1186/1471-2148-8-195
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发表时间：
2008-07-07
影响因子：
3.4
通讯作者：
Laan, Maris
中科院分区：
文献类型：
--
作者：
Hallast, Pille;Saarela, Janna;Laan, Maris
背景：人类和黑猩猩之间的低核苷酸差异并不能充分解释物种特异性的形态、生理和行为特征。由于基因复制是新基因和新生物过程出现的主要先决条件，因此对人类和黑猩猩复制基因的比较研究可能有助于理解灵长类动物进化背后的机制。我们通过使用黄体生成素 Beta (LHB)/绒毛膜促性腺激素 Beta (CGB) 基因簇作为模型来解决人类和黑猩猩重复基因组区域之间的差异。对着床至关重要的胎盘 CGB 基因是通过灵长类谱系中的复制从祖先垂体 LHB 基因进化而来的。结果：我们对人类 (45,165 bp) 和黑猩猩 (39,876 bp) LHB/CGB 区域进行了鸟枪法测序和比较，并在此提供了导致 CGB 基因数量不一致的结构变异的证据（人类 6 个，黑猩猩 5 个）。支持物种特异性平行复制的方案（i）作为最简约的解决方案，需要最少的重排事件来解释物种间的结构差异； (ii) 通过用基因间区域片段构建的系统发育树； (iii)通过序列相似性计算。在 LHB/CGB 簇的直系同源区域中，替换和插入缺失对种间差异的贡献大致相同，并且核苷酸同一性的分布与区域重复内容相关。种内基因转换可能塑造了 LHB/CGB 基因簇。取代分歧 (1.8-2.59%) 超过单拷贝基因座估计值的两到三倍，并且与独特序列相比，颠换突变的比例有所增加（43% 与相似的 30%）。尽管 LHB/CGB 基因之间具有很高的序列同一性，但基因拷贝之间存在功能分化的迹象。对 d(n)/d(s) 比率的估计表明 LHB 和 CGB8 的纯化选择，以及 CGB1 的正向进化。结论：如果概括的话，我们的数据表明，除了物种特异性的删除和重复之外，平行的重复事件可能导致了人类与其近亲之间的遗传差异。与独特的基因组片段相比，重复区域的特点是物种内基因转换和物种特异性染色体重排（包括基因拷贝数的改变）促进的高度分歧。
Background: Low nucleotide divergence between human and chimpanzee does not sufficiently explain the species-specific morphological, physiological and behavioral traits. As gene duplication is a major prerequisite for the emergence of new genes and novel biological processes, comparative studies of human and chimpanzee duplicated genes may assist in understanding the mechanisms behind primate evolution. We addressed the divergence between human and chimpanzee duplicated genomic regions by using Luteinizing Hormone Beta (LHB)/Chorionic Gonadotropin Beta (CGB) gene cluster as a model. The placental CGB genes that are essential for implantation have evolved from an ancestral pituitary LHB gene by duplications in the primate lineage.Results: We shotgun sequenced and compared the human (45,165 bp) and chimpanzee (39,876 bp) LHB/CGB regions and hereby present evidence for structural variation resulting in discordant number of CGB genes (6 in human, 5 in chimpanzee). The scenario of species-specific parallel duplications was supported (i) as the most parsimonious solution requiring the least rearrangement events to explain the interspecies structural differences; (ii) by the phylogenetic trees constructed with fragments of intergenic regions; (iii) by the sequence similarity calculations. Across the orthologous regions of LHB/CGB cluster, substitutions and indels contributed approximately equally to the interspecies divergence and the distribution of nucleotide identity was correlated with the regional repeat content. Intraspecies gene conversion may have shaped the LHB/CGB gene cluster. The substitution divergence ( 1.8-2.59%) exceeded two-three fold the estimates for single-copy loci and the fraction of transversional mutations was increased compared to the unique sequences (43% versus similar to 30%). Despite the high sequence identity among LHB/CGB genes, there are signs of functional differentiation among the gene copies. Estimates for d(n)/d(s) rate ratio suggested a purifying selection on LHB and CGB8, and a positive evolution of CGB1.Conclusion: If generalized, our data suggests that in addition to species-specific deletions and duplications, parallel duplication events may have contributed to genetic differences separating humans from their closest relatives. Compared to unique genomic segments, duplicated regions are characterized by high divergence promoted by intraspecies gene conversion and species-specific chromosomal rearrangements, including the alterations in gene copy number.