Immune System Promiscuity in Human and Nonhuman Primate Evolution
Immune System Promiscuity in Human and Nonhuman Primate Evolution
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DOI：
10.13110/humanbiology.90.4.01
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发表时间：
2018-11
期刊：
影响因子：
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通讯作者：
Jessica F. Brinkworth;C. Babbitt
中科院分区：
文献类型：
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作者：
Jessica F. Brinkworth;C. Babbitt
摘要 许多对感染做出反应的基因具有免疫之外的功能，并且已被发现处于自然选择之下。因此，病原体可能通过与免疫系统基因的接触而偶然改变非免疫生理学。这就提出了一个逻辑问题：免疫系统在遗传上有多混杂，这里定义为免疫系统与其他生理系统的交叉引用程度。这项工作通过评估关键组织和细胞类型的基线（未受干扰）表达的差异以及灵长类基因组的选择特征来检查灵长类动物生理系统中的免疫基因混杂性。这些努力揭示了“免疫”基因表达可以在灵长类动物的其他生理系统中广泛交叉引用。当免疫组织和非免疫组织的表达出现差异时，基线时差异表达的基因会因细胞生物学活性而富集，而不能立即识别为基于免疫功能。对灵长类动物免疫和非免疫组织的个体比较显示，除全血外，组织之间的基因表达差异较小。随着进化时间的推移，免疫基因混杂性不断增加，类人猿在灵长类动物中表现出最多的此类基因的交叉引用。对基因序列的评估还发现，与免疫功能相关的组织之间差异表达基因的编码区存在正向选择。这表明，随着混杂性的增加，免疫系统和其他生理系统之间的不同基因表达往往会适应并丰富类人猿的免疫功能。
abstract Many genes that respond to infection have functions outside of immunity and have been found to be under natural selection. Pathogens may therefore incidentally alter nonimmune physiology through engagement with immune system genes. This raises a logical question of how genetically promiscuous the immune system is, here defined as how heavily cross-referenced the immune system is into other physiological systems. This work examined immune gene promiscuity across physiological systems in primates by assessing the baseline (unperturbed) expression of key tissue and cell types for differences, and primate genomes for signatures of selection. These efforts revealed “immune” gene expression to be cross-referenced extensively in other physiological systems in primates. When immune and nonimmune tissues diverge in expression, the differentially expressed genes at baseline are enriched for cell biological activities not immediately identifiable as immune function based. Individual comparisons of immune and nonimmune tissues in primates revealed low divergence in gene expression between tissues, with the exception of whole blood. Immune gene promiscuity increases over evolutionary time, with hominoids exhibiting the most cross-referencing of such genes among primates. An assessment of genetic sequences also found positive selection in the coding regions of differentially expressed genes between tissues functionally associated with immunity. This suggests that, with increasing promiscuity, divergent gene expression between the immune system and other physiological systems tends to be adaptive and enriched for immune functions in hominoids.