HLA diversity, differentiation, and haplotype evolution in Mesoamerican Natives

Area of Science:

• Immunogenetics
• Population Genetics
• Human Evolutionary Genetics

Background:

• The Human Leukocyte Antigen (HLA) region is crucial for immune response and exhibits high genetic diversity.
• Understanding HLA variation in indigenous populations like those in Oaxaca provides insights into human migration and adaptation.
• Previous studies on Amerindian populations have shown unique HLA profiles, but comprehensive analysis across multiple loci is often limited.

Purpose of the Study:

• To investigate the genetic variation and evolutionary forces shaping the HLA region in three distinct Amerindian groups from Oaxaca, Mexico: Zapotec, Mixtec, and Mixe.
• To identify novel HLA alleles and assess the extent of European admixture in these populations.
• To determine whether selection (balancing or directional) or random genetic drift has shaped the observed allele frequency distributions.

Main Methods:

• Genotyping of Human Leukocyte Antigen (HLA) class I (HLA-A, -B, -C) and class II (DRB1, DQA1, DQB1, DPB1) loci using Polymerase Chain Reaction Sequence-Specific Oligonucleotide Probes (PCR-SSOP).
• Analysis of genotype and allele frequencies, Hardy-Weinberg equilibrium, and linkage disequilibrium.
• Statistical tests were employed to detect deviations from neutrality and identify signatures of selection.

Main Results:

• New alleles were identified at class I HLA loci. European admixture was estimated between 1% and 10% and excluded from further analysis.
• Allele frequencies at DRB1, DQA1, DQB1, and HLA-A loci showed distributions more even than expected under neutrality, suggesting balancing selection.
• Evidence for directional selection was found at the DPB1 locus due to significantly higher than expected homozygosity. HLA-B and HLA-C loci did not significantly deviate from neutrality.
• Strong linkage disequilibrium was observed across the HLA region, indicating non-random associations between alleles at different loci, except for those involving DPB1.

Conclusions:

• The HLA region in Oaxacan Amerindians is shaped by a combination of evolutionary forces, including balancing selection at several loci and directional selection at DPB1.
• The observed linkage disequilibrium patterns suggest strong selective pressures maintaining specific haplotypes across the HLA region.
• These findings contribute to understanding the genetic history and adaptive processes within indigenous Mexican populations.