Interleukin-37 gene variants segregated anciently coexist during hominid evolution
Interleukin-37 gene variants segregated anciently coexist during hominid evolution
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在原始人类进化过程中，白细胞介素 37 基因变体在古代是共存的。
DOI：
10.1038/ejhg.2014.302
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发表时间：
2015-10-01
影响因子：
5.2
通讯作者：
Zhang, Shuye
中科院分区：
文献类型：
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作者：
Kang, Bin;Cheng, Shimeng;Zhang, Shuye
IL 37是IL-1细胞因子家族的成员，但具有抗炎功能。IL 37的生物学特性和遗传异质性尚未完全清楚。在这里，我们使用1000个基因组计划的全基因组测序数据，对人类IL 37基因进行了群体和进化遗传学分析。首先，从不同人群中检索到2184个IL 37基因序列。从编码DNA序列推断IL 37蛋白序列，并进行多物种比对。构建了IL 37的系统发育树，计算了各进化分支的dN/dS比值，并进行了经典的McDonald和Kreitman检验。接下来，我们进行了种内进化遗传分析，并通过中位数连接网络分析建立了116个独特的IL 37单倍型的系谱网络。最后，我们比较了现代人和古代人之间的IL 37序列。我们的研究结果首次提供了坚实的证据，证明除NCBI参考序列外，世界范围内存在常见的IL 37变体。我们的数据还支持IL 37变体是通过选择而不是中性进化形成和维持的。我们进一步鉴定了人IL 37变体由两个主要单倍型群组成，并且它们在古人类中的存在证实了其在原始人类进化中的古老起源。总之，这些数据表明，通过选择力在人群中维持常见的IL 37变体，表明它们可能参与免疫调节和人类疾病。此外，IL 37变体的古老历史揭示了对复杂的人类进化史的有趣见解。
IL37 is a member of IL-1 cytokine family but conveys anti-inflammatory functions. The biological characteristic and genetic heterogeneity of IL37 are not fully understood yet. Here using the whole-genome sequencing data from 1000 Genomes Project, we performed population and evolutionary genetic analysis of human IL37 gene. First, 2184 IL37 gene sequences from different human populations were retrieved. The IL37 protein sequences were inferred from the coding DNA sequences and multiple species alignment was made. Then, the phylogenetic tree of IL37 was built and dN/dS ratios were calculated for each evolutionary branch, the classic McDonald and Kreitman test was also performed. Next, we conducted intraspecific evolutionary genetic analysis and built the genealogy network of 116 unique IL37 haplotypes through median-joining network analysis. Finally, we compared IL37 sequences between the modern and archaic humans. Our results for the first time provide solid evidence that common IL37 variants other than NCBI reference sequence are present worldwide. Our data also supports that IL37 variants are shaped and maintained by selection instead of neutral evolution. We further identified that human IL37 variants consist of two major haplogroups and their presence in archaic humans corroborates its ancient origin in hominid evolution. In conclusion, these data indicate that common IL37 variants are maintained among human populations by selective force, suggesting their potential involvements in immune regulation and human diseases. In addition, the ancient history of IL37 variants reveals interesting insight into the complicated human evolutionary history.