Identification and Characterization of Lineage-Specific Highly Conserved Noncoding Sequences in Mammalian Genomes
Identification and Characterization of Lineage-Specific Highly Conserved Noncoding Sequences in Mammalian Genomes
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脊椎动物基因组比较显示，有高度保守的非编码序列（HCNSs）之间的广泛的物种，其中许多含有调控元件。然而，最近出现的特定谱系中保守的序列尚未得到很好的研究。为此，我们分别从人-绒猴和小鼠-大鼠的比较中确定了艾德8，198种灵长类动物和21，128种特异性HCNS作为哺乳动物中的代表性HCNS。灵长类特异性HCNSs的衍生等位基因频率分析表明，这些HCNSs处于纯化选择中，表明它们可能具有重要功能。我们选择了前1,000个最大的HCNS，并将谱系特异性HCNS-测序基因（LHF基因）与超保守元件（UCE）-测序基因进行了比较。有趣的是，大多数LHF基因与UCE-标记基因不同。这种谱系特异性的LHF基因集在蛋白结合功能方面更加丰富。相反，UCE共享的LHF基因数量很少，但明显大于随机预期，并且这些基因中的许多基因作为转录调节因子参与解剖发育，这表明某些基因组除了在脊椎动物中保守的旧HCNS之外，还优先招募新的HCNS。这组LHF基因可能参与脊椎动物、哺乳动物、灵长类动物和啮齿类动物之间不同水平的谱系特异性进化。如果是这样的话，在这两组LHF基因中及其周围出现的HCNSs就形成了谱系特异性特征。我们的研究结果通过HCNSs与其LHF基因之间的相互作用为谱系特异性进化提供了新的见解。
Vertebrate genome comparisons revealed that there are highly conserved noncoding sequences (HCNSs) among a wide range of species and many of which contain regulatory elements. However, recently emerged sequences conserved in specific lineages have not been well studied. Toward this end, we identified 8,198 primate and 21,128 specific HCNSs as representative ones among mammals from human–marmoset and mouse–rat comparisons, respectively. Derived allele frequency analysis of primate-specific HCNSs showed that these HCNSs were under purifying selection, indicating that they may harbor important functions. We selected the top 1,000 largest HCNSs and compared the lineage-specific HCNS-flanking genes (LHF genes) with ultraconserved element (UCE)-flanking genes. Interestingly, the majority of LHF genes were different from UCE-flanking genes. This lineage-specific set of LHF genes was more enriched in protein-binding function. Conversely, the number of LHF genes that were also shared by UCEs was small but significantly larger than random expectation, and many of these genes were involved in anatomical development as transcriptional regulators, suggesting that certain groups of genes preferentially recruit new HCNSs in addition to old HCNSs that are conserved among vertebrates. This group of LHF genes might be involved in the various levels of lineage-specific evolution among vertebrates, mammals, primates, and rodents. If so, the emergence of HCNSs in and around these two groups of LHF genes developed lineage-specific characteristics. Our results provide new insight into lineage-specific evolution through interactions between HCNSs and their LHF genes.