So far, at least six models have been suggested to explain the maintenance of MHC variability, the two most prominent ones being a) balancing selection and b) the rare allele model [ 25].
Each of the genomes of this heteroplasmic line has a defect complemented by the other so that the line is healthy but neither genomes is lost, a balancing selection (Ma et al., 2014).
Alternatively, it could be maintained by a balancing selection process [ 36, 37].
Interestingly, we also found a much less marked divergence between Asian and European haplotypes than found with genome wide markers; that, together with the high variability, may be indicative of a balancing selection at these loci, in particular for bitter taste receptors.
From the point of view of the selective forces driving evolution, a significantly positive value of D is compatible with a balancing selection preventing a single allele from being fixed in the population and maintaining an higher than expected level of diversity.
As the majority of functionally important sites in the best model variant belongs to the intersection between the DNase I accessibility region and experimentally characterized CRMs, we conclude that there should be a balance in binding site selection for modeling gene regulation.
The binding energy distributions show that for a general genotype phenotype map fitness is not maximized, but instead there is a balance between selection for higher fitness and the tendency to undergo drift toward those phenotypes that correspond to the largest number of sequences.
The likelihood ratio test of hypotheses (M2a vs M1a and M8 vs M7) showed statistically significant values (P < 0.001), suggesting a balancing selection model is a better fit to the data compared to other models.
The majority of clear evidence for selection was found to be balancing selection in these genes, with the exception of RPS4, which has undergone a recent selective sweep [ 40].
For example a polymorphism underlying a robustness QTL could be under balancing selection, or could be currently undergoing a selective sweep; different alleles could have been fixed in different (normally isolated) populations that were each advantageous to their own environments; or the robustness QTL observed in laboratory settings might not be expressed as such in the wild.
