HLA-G genetic diversity and evolutive aspects in worldwide populations.

Castelli, ECORCID logo; de Almeida, BS; Muniz, YC; Silva, NS; Passos, MR; Souza, AS; Page, AEORCID logo; Dyble, M; Smith, D; Aguileta, G; +10 more...Bertranpetit, J; Migliano, AB; Duarte, YA; Scliar, MO; Wang, J; Passos-Bueno, MR; Naslavsky, MS; Zatz, M; Mendes-Junior, CT; Donadi, EA and (2021) HLA-G genetic diversity and evolutive aspects in worldwide populations. Scientific reports, 11 (1). 23070-. ISSN 2045-2322 DOI: 10.1038/s41598-021-02106-4
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HLA-G is a promiscuous immune checkpoint molecule. The HLA-G gene presents substantial nucleotide variability in its regulatory regions. However, it encodes a limited number of proteins compared to classical HLA class I genes. We characterized the HLA-G genetic variability in 4640 individuals from 88 different population samples across the globe by using a state-of-the-art method to characterize polymorphisms and haplotypes from high-coverage next-generation sequencing data. We also provide insights regarding the HLA-G genetic diversity and a resource for future studies evaluating HLA-G polymorphisms in different populations and association studies. Despite the great haplotype variability, we demonstrated that: (1) most of the HLA-G polymorphisms are in introns and regulatory sequences, and these are the sites with evidence of balancing selection, (2) linkage disequilibrium is high throughout the gene, extending up to HLA-A, (3) there are few proteins frequently observed in worldwide populations, with lack of variation in residues associated with major HLA-G biological properties (dimer formation, interaction with leukocyte receptors). These observations corroborate the role of HLA-G as an immune checkpoint molecule rather than as an antigen-presenting molecule. Understanding HLA-G variability across populations is relevant for disease association and functional studies.


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