A General Model of Negative Frequency Dependent Selection Explains Global Patterns of Human ABO Polymorphism - PubMed (original) (raw)

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

Fernando A Villanea et al. PLoS One. 2015.

Abstract

The ABO locus in humans is characterized by elevated heterozygosity and very similar allele frequencies among populations scattered across the globe. Using knowledge of ABO protein function, we generated a simple model of asymmetric negative frequency dependent selection and genetic drift to explain the maintenance of ABO polymorphism and its loss in human populations. In our models, regardless of the strength of selection, models with large effective population sizes result in ABO allele frequencies that closely match those observed in most continental populations. Populations must be moderately small to fall out of equilibrium and lose either the A or B allele (N(e) ≤ 50) and much smaller (N(e) ≤ 25) for the complete loss of diversity, which nearly always involved the fixation of the O allele. A pattern of low heterozygosity at the ABO locus where loss of polymorphism occurs in our model is consistent with small populations, such as Native American populations. This study provides a general evolutionary model to explain the observed global patterns of polymorphism at the ABO locus and the pattern of allele loss in small populations. Moreover, these results inform the range of population sizes associated with the recent human colonization of the Americas.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1

Fig 1. Pattern of isolation by distance at neutral markers and the ABO locus.

The dashed grey line is based upon a regression analysis of heterozygosity at 678 autosomal short tandem repeats with migration distance from East Africa43. A similar regression was conducted using expected ABO heterozygosity, given allele frequencies at this locus (S2 Table). Native American populations (grey solid line) present a slope significantly different than zero (β = -2.532 x 10–5, P<<0.05), while non-Native American (black solid line) populations do not (β = -2.171 x 10–6, P = 0.0895).

Fig 2

Fig 2. Reduction in ABO expected heterozygosity for different strengths of selection (z = 0.00 denotes neutrality).

Results after 100 generations of selection and drift are shown across a range of log-transformed population sizes (N e). Simulations were conducted at untransformed N e values of N e = 10, 25, 50, 100, 250, 500, and 1,000.

Fig 3

Fig 3. The relationship between ABO heterozygosity and log-transformed N e based upon model expectations for weak selection (z = 0.25), moderate selection (z = 0.5) and strong selection (z = 0.75).

Simulations were conducted at untransformed N e values of N e = 10, 25, 50, 100, 250, 500, and 1,000. Expected values of ABO heterozygosity are also shown for various non-Native American, North Native American, and South Native American populations.

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