Evolutionary immuno-genetics of endoplasmic reticulum aminopeptidase II (ERAP2)

• Published in: Genes and immunity Vol. 24; no. 6; pp. 295 - 302
• Main Authors: Raja, Aroosha, Kuiper, Jonas J W
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.12.2023
• Subjects: Adaptation; Adaptive immunity; Adaptive Immunity - genetics; Allotypes; Amino acids; Aminopeptidase; Aminopeptidases - genetics; Aminopeptidases - immunology; Antigens; Autoimmune diseases; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Disease; Endoplasmic reticulum; Endoplasmic Reticulum - enzymology; Enzymes; Evolution; Evolution, Molecular; Genes; Genomes; Haplotypes; Humans; Infectious diseases; Inflammatory diseases; Lymphocytes; Minor Histocompatibility Antigens - genetics; Nucleotide sequence; Peptides; Proteins; Proteolysis
• ISSN: 1476-5470; 1466-4879; 1476-5470
• DOI: 10.1038/s41435-023-00225-8

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.