Characterization and evolution of the novel gene family FAM90A in primates originated by multiple duplication and rearrangement events
Characterization and evolution of the novel gene family FAM90A in primates originated by multiple duplication and rearrangement events
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DOI：
10.1093/hmg/ddm209
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发表时间：
2007-11-01
影响因子：
3.5
通讯作者：
Estivill, Xavier
中科院分区：
文献类型：
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作者：
Bosch, Nina;Caceres, Mario;Estivill, Xavier
人类染色体8p23.1区域的基因组可塑性受到两组复杂的片段重复（SDs）的高度影响，称为REPD和REPP，它们介导不同类型的重排。解释与8p23.1重排相关的广泛表型的困难部分在于REPP和REPD尚未得到很好的表征，可能是由于它们的多态性状态。在这里，我们描述了一个新的灵长类动物特异性基因家族，命名为FAM 90 A（家庭与序列相似性90），发现在这些SD。根据目前的人类参考序列组装，FAM 90 A家族包括沿着8p23.1区域的24个成员加上染色体12p13.31上的单个成员，显示个体之间的拷贝数变异（copy number variation，CNV）。这些基因可分为亚家族I和II，它们的上游和5 '-非翻译区序列不同，但两者共享相同的开放阅读框架，并且普遍表达。序列分析和比较荧光原位杂交研究表明，FAM 90 A亚家族II遭受了很大的扩张，在类人猿谱系，而亚家族I成员可能产生的猩猩和非洲大猿的分歧，通过融合过程的某个时候。此外，Ka/Ks比值的分析提供了一些FAM 90 A基因在所有物种中的功能限制的证据。FAM 90 A基因家族的表征有助于更好地理解人类8p23.1区域的结构多态性，并构成了SD、CNV和自身重排如何促进具有潜在功能后果的新基因序列形成的良好实例。
Genomic plasticity of human chromosome 8p23.1 region is highly influenced by two groups of complex segmental duplications (SDs),termed REPD and REPP, that mediate different kinds of rearrangements. Part of the difficulty to explain the wide range of phenotypes associated with 8p23.1 rearrangements is that REPP and REPD are not yet well characterized, probably due to their polymorphic status. Here, we describe a novel primate-specific gene family, named FAM90A (family with sequence similarity 90), found within these SDs. According to the current human reference sequence assembly, the FAM90A family includes 24 members along 8p23.1 region plus a single member on chromosome 12p13.31, showing copy number variation (CNV) between individuals. These genes can be classified into subfamilies I and II, which differ in their upstream and 5 '-untranslated region sequences, but both share the same open reading frame and are ubiquitously expressed. Sequence analysis and comparative fluorescence in situ hybridization studies showed that FAM90A subfamily II suffered a big expansion in the hominoid lineage, whereas subfamily I members were likely generated sometime around the divergence of orangutan and African great apes by a fusion process. In addition, the analysis of the Ka/Ks ratios provides evidence of functional constraint of some FAM90A genes in all species. The characterization of the FAM90A gene family contributes to a better understanding of the structural polymorphism of the human 8p23.1 region and constitutes a good example of how SDs, CNVs and rearrangements within themselves can promote the formation of new gene sequences with potential functional consequences.