Role of gene conversion in generating polymorphisms at major histocompatibility complex loci

Area of Science:

• Population Genetics
• Molecular Evolution
• Immunogenetics

Background:

• Multigene families, including major histocompatibility complex (MHC) loci, evolve through processes like unequal crossing-over and gene conversion.
• Understanding the evolutionary dynamics of MHC genes is crucial due to their role in immune response and disease susceptibility.

Purpose of the Study:

• To investigate the effects of diversifying selection and gene conversion on MHC polymorphisms using population genetic models.
• To explore mechanisms driving rapid allelic turnover in MHC genes, particularly in the context of South American Indian populations.

Main Methods:

• Computer simulations of population genetic models incorporating intra- and inter-locus gene conversion.
• Modeling of both global and endemic types of diversifying selection, including scenarios with strong selection leading to lethal alleles.

Main Results:

• Weak selection at individual amino acid sites effectively enhances polymorphism when gene conversion is present, promoting coadapted mutation segments.
• Periodic endemic selection can accelerate allelic turnover via intralocus gene conversion, explaining rapid changes in MHC allele frequencies.
• The interplay between selection and gene conversion profoundly influences MHC polymorphism levels.

Conclusions:

• Gene conversion is a key evolutionary force shaping MHC diversity, particularly when acting in concert with selection.
• Specific selection pressures, such as endemic balancing selection, can drive rapid MHC allelic turnover.
• These findings provide insights into the complex evolutionary mechanisms maintaining high MHC diversity.