Heterozygote advantage cannot explain MHC diversity, but MHC diversity can explain heterozygote advantage
- Computational Biology Branch, Division of Intramural Research, National Library of Medicine, National Institutes of Health, United States
Figures
Figure 1
Haplotype expansion can increase mean fitness and elimate heterozygote advantage.
(A) A population with polymorphism and heterozygote advantage. The population includes high-fitness heterozygotes and low-fitness homozygotes. (B) A haplotype bearing two alleles in tandem forms high-fitness homozygotes. A population monomorphic for such a haplotype consists of only high-fitness individuals.
Figure 2 with 1 supplement
Small changes to parameter values largely eliminate MHC diversity in the Gaussian model.
The plot shows diversity over time in simulations with parameter values that lead to high diversity (red curve) and with slightly altered parameter values but no compensatory adjustment of cmax. The bottom panel is a vertical zoom of the top panel.
Figure 2—figure supplement 1
Simulation results for the bitstring model with various values of parameters m and v and identical values of other parameters, including cmax.
One hundred simulation runs are represented in each plot. Equilibrium diversity is high with m=100 and v=20 (A), but low if these parameters are changed slightly (B–E). The thick black curve in some of the plots (B), (D), and (E) represents the harmonic mean among runs.
Figure 3
Gene family expansion in the Gaussian model.
Top: diversity over time in 20 simulation runs. In each run, haplotypes bearing two alleles come to predominate, leading to a sudden loss of any diversity that has accumulated. Bottom: the distribution of time until such an event in 10,000 simulation runs.
Figure 4
Diversity over time in simulations of the bitstring model with gene family expansion.
20 simulation runs are shown. Diversity becomes and remains low when expanded haplotypes come to predominate.
Figure 5
Diversity over time in simulations with gene family expansion but only weak expression of additional alleles carried by a haplotype.
Top: Gaussian model. Bottom: bitstring model.
Figure 6 with 2 supplements
Simulation results for a model in which mutation can alter the breadth of peptides presented.
The initial allele specifies v=9, and cmax is set accordingly. Mutation can change v to 8.12 (top) or 8.9 (bottom). Results of one hundred simulation runs are shown in each plot.
Figure 6—figure supplement 1
Simulations like those in Figure 6, top, except that diversity is allowed to accumulate for 1 million generations before mutations affecting the breadth of presentation are allowed.
In all 20 runs, diversity collapses quickly once such mutations are allowed. The bottom panel is a horizontal zoom of the top panel.
Figure 6—figure supplement 2
Simulations incorporating a 50% decrease in all peptide detection probabilities in individuals with certain genotypes.
Other conditions are as in Figure 6, top. Despite the inclusion of this effect, alleles with higher presentation breadth quickly come to predominate, preventing the development of high diversity.
Figure 7
Diversity over time in simulations of the bitstring model in which v can evolve between 9 and 8.12 and overly wide presentation breadth is lethal.
The initial allele has narrow presentation breadth (v=9) in the top panel and broader presentation breadth (v=8.12) in the bottom panel. One hundred simulation runs are shown for each. Note that many curves in both plots fall on top of each other, with effective number of alleles close to 1 throughout the simulations.
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Heterozygote advantage cannot explain MHC diversity, but MHC diversity can explain heterozygote advantage
eLife 14:RP107256.
https://doi.org/10.7554/eLife.107256.3
