Strong Selection at MHC in Mexicans since Admixture.

Area of Science:

• Human genetics
• Population genetics
• Evolutionary biology

Background:

• Mexicans represent a recent admixture of Indigenous American, European, and African ancestries.
• Previous genetic studies in Latino populations faced challenges due to inaccurate ancestral training data.
• The Major Histocompatibility Complex (MHC) region is crucial for immune function and is known to be under selection.

Purpose of the Study:

• To investigate local ancestry and identify recent selection signals in the Mexican population.
• To address concerns regarding the accuracy of ancestral inference in admixed populations.
• To determine if strong selection is present in the MHC region of Mexicans.

Main Methods:

• Local ancestry analysis was performed on Mexican samples from two genome-wide association studies.
• A novel statistical model was developed to infer Amerindian haplotypes directly from admixed samples, using only European and African training data.
• Selection coefficients were estimated to quantify the strength of observed selection signals.

Main Results:

• Mexicans exhibit a significantly higher proportion of African ancestral alleles in the MHC region compared to other genomic regions.
• Estimated selection coefficients (0.05 and 0.07) indicate selection pressures in the MHC region comparable to strong known human adaptations.
• The robust MHC selection signal persisted even when Amerindian training samples were excluded from the analysis.

Conclusions:

• Recent and strong positive selection acting on African ancestry has occurred in the MHC region of the Mexican population.
• The developed statistical method overcomes limitations of previous ancestral inference techniques in admixed groups.
• The findings suggest a potential adaptive advantage related to immune function in the MHC region for Mexicans, supported by medical history.