Did variants in inborn errors of immunity genes contribute to the extinction of Neanderthals?

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Abstract

Background: Neanderthals were a species of archaic humans that became extinct around 40,000 years ago. Modern humans have inherited 1-6% of Neanderthal DNA as a result of interbreeding. These inherited Neanderthal genes have paradoxical influences, while some can provide protection to viral infections, some others are associated with autoimmune/auto-inflammatory diseases. Objective: We aim to investigate whether genetic variants with strong detrimental effects on the function of the immune system could have potentially contributed to the extinction of the Neanderthal population. Methods: We used the publically available genome information from an Altai Neanderthal and filtered for potentially damaging variants present in genes associated with inborn errors of immunity (IEI) and checked whether these variants were present in the genomes of the Denisovan, Vindija and Chagyrskaya Neanderthals. Results: We identified 24 homozygous variants and 15 heterozygous variants in IEI-related genes in the Altai. Neanderthal. Two homozygous variants in the UNC13D gene and one variant in the MOGS gene were present in all archaic genomes. Defects in the UNC13D gene are known to cause a severe and often fatal disease called. hemophagocytic lymphohistiocystosis (HLH). One of these variants p.(N943S) has been reported in patients with HLH. Variants in MOGS are associated with glycosylation defects in the immune system affecting the susceptibility for infections. Conclusion: Although the exact functional impact of these three variants needs further elucidation, we speculate that they could have resulted in an increased susceptibility to severe diseases and may have contributed to the extinction of Neanderthals after exposure to specific infections.

Original languageEnglish
Pages (from-to)422-434
Number of pages13
JournalAsian Pacific Journal of Allergy and Immunology
Volume40
Issue number4
DOIs
Publication statusPublished - 1 Dec 2022

Bibliographical note

Funding Information:
The research for this manuscript was performed within the framework of the Erasmus Postgraduate School of Molecular Medicine. This work was supported by the China Scholarship Council for funding PhD fellowships. (No.201908440363 Z.Z). The authors have no conflict of interest.

Publisher Copyright:
© 2022, Allergy and Immunology Society of Thailand. All rights reserved.

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