A General Model of Negative Frequency Dependent Selection Explains Global Patterns of Human ABO Polymorphism

Area of Science:

• Human population genetics
• Evolutionary biology
• Molecular anthropology

Background:

• The ABO blood group locus exhibits high heterozygosity and uniform allele frequencies globally.
• Understanding the evolutionary forces shaping ABO polymorphism is crucial for human population studies.

Purpose of the Study:

• To model the maintenance and loss of ABO polymorphism using asymmetric negative frequency-dependent selection and genetic drift.
• To correlate model outcomes with observed global ABO allele frequencies and patterns in specific populations.

Main Methods:

• Developed a computational model incorporating selection and genetic drift.
• Simulated ABO allele frequency dynamics across various effective population sizes.
• Compared model predictions with empirical data from human populations.

Main Results:

• Large effective population sizes maintain ABO allele frequencies similar to global observations.
• Moderate population sizes (N(e) ≤ 50) lead to loss of A or B alleles.
• Small population sizes (N(e) ≤ 25) result in near-complete loss of ABO diversity, often with O allele fixation.

Conclusions:

• The model successfully explains global ABO polymorphism and allele loss in small populations.
• Observed low heterozygosity in Native American populations aligns with model predictions for small populations.
• Results provide insights into population sizes relevant to the peopling of the Americas.