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Title: The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation

item SCHWARTZ, JOHN - Pirbright Laboratory
item GIBSON, MARK - Pirbright Laboratory
item HEIMEIER, DOROTHEA - Pirbright Laboratory
item KOREN, SERGEY - National Institutes Of Health (NIH)
item PHILLIPPY, ADAM - National Institutes Of Health (NIH)
item Bickhart, Derek
item Smith, Timothy - Tim
item MEDRANO, JUAN - University Of California
item HAMMOND, JOHN - Pirbright Laboratory

Submitted to: Immunogenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2017
Publication Date: 2/7/2017
Citation: Schwartz, J.C., Gibson, M.S., Heimeier, D., Koren, S., Phillippy, A.M., Bickhart, D.M., Smith, T.P., Medrano, J.F., Hammond, J.A. 2017. The evolution of the natural killer complex; a comparison between mammals using new high-quality genome assemblies and targeted annotation. Immunogenetics. 69(2):255-269.

Interpretive Summary: Mammalian immune gene regions control a large portion of innate and adaptive immunity to bacterial and viral pathogens; however, their polymorphic nature and diversity in animal populations makes them very difficult to assemble into a reference dataset. Use of new sequencing technologies has improved our ability to identify and characterize these regions, and may result in the development of new methods of tracking particularly effective variants of these regions. This manuscript compares and contrasts older reference assemblies with newer assemblies that use these new sequencing methods and shows a clear improvement of characterization.

Technical Abstract: Natural killer (NK) cells are a diverse population of lymphocytes with a range of biological roles including essential immune functions. NK cell diversity is created by the differential expression of cell surface receptors which modulate activation and function, including multiple subfamilies of C-type lectin receptors encoded within the NK gene complex (NKC). Little is known about the gene content of the NKC beyond rodent and primate lineages, other than it appears to be extremely variable between mammalian groups. We compared the NKC structure between mammalian species using new high quality draft genome assemblies for cattle and goat, re-annotated sheep, pig and horse genome assemblies and the published human, rat and mouse lemur NKC. The major NKC genes are largely in syntenic positions in all eight species, with significant independent expansions and deletions between species, allowing us to present a model for NKC evolution during mammalian radiation. The ruminant species, cattle and goats, have independently evolved a second KLRC locus flanked by KLRA and KLRJ and a novel KLRH-like gene has acquired an activating tail. This novel gene has duplicated several times within cattle, while other activating receptor genes have been selectively disrupted. Targeted genome enrichment in cattle identified varying levels of allelic polymorphism between these NKC genes concentrated in the predicted extracellular ligand binding domains. This novel recombination and allelic polymorphism is consistent with NKC evolution under balancing selection, suggesting this diversity influences individual immune responses and may impact on differential outcomes of pathogen infection and vaccination.