Department of Ophthalmology, Center for Translational Immunology, University Medical Center Utrecht, University of Utrecht, Utrecht, The Netherlands.
Genes Immun. 2023 Dec;24(6):295-302. doi: 10.1038/s41435-023-00225-8. Epub 2023 Nov 4.
Endoplasmic reticulum aminopeptidase 2 (ERAP2) is a proteolytic enzyme involved in adaptive immunity. The ERAP2 gene is highly polymorphic and encodes haplotypes that confer resistance against lethal infectious diseases, but also increase the risk for autoimmune disorders. Identifying how ERAP2 influences susceptibility to these traits requires an understanding of the selective pressures that shaped and maintained allelic variation throughout human evolution. Our review discusses the genetic regulation of haplotypes and diversity in naturally occurring ERAP2 allotypes in the global population. We outline how these ERAP2 haplotypes evolved during human history and highlight the presence of Neanderthal DNA sequences in ERAP2 of modern humans. Recent evidence suggests that human adaptation during the last ~10,000 years and historic pandemics left a significant mark on the ERAP2 gene that determines susceptibility to infectious and inflammatory diseases today.
内质网氨肽酶 2（ERAP2）是一种参与适应性免疫的蛋白水解酶。ERAP2 基因高度多态性，其编码的单倍型既能抵抗致命的传染病，又能增加自身免疫性疾病的风险。要了解 ERAP2 如何影响这些特征的易感性，就需要了解塑造和维持人类进化过程中等位基因变异的选择压力。我们的综述讨论了全球人群中 ERAP2 自然发生的同种型的遗传调控和多样性。我们概述了这些 ERAP2 单倍型在人类历史上是如何进化的，并强调了现代人类 ERAP2 中存在尼安德特人 DNA 序列。最近的证据表明，人类在过去约 10000 年的适应过程和历史大流行对 ERAP2 基因留下了显著的印记，该基因决定了人类对传染性和炎症性疾病的易感性。
