The fitness consequences of genetic divergence between polymorphic gene arrangements

Abstract

Inversions restrict recombination when heterozygous with standard arrangements, but often have few noticeable phenotypic effects. Nevertheless, there are several examples of inversions that can be maintained polymorphic by strong selection under laboratory conditions. A long-standing model for the source of such selection is divergence between arrangements with respect to recessive or partially recessive deleterious mutations, resulting in a selective advantage to heterokaryotypic individuals over homokaryotypes. This paper uses a combination of analytical and numerical methods to investigate this model, for the simple case of an autosomal inversion with multiple independent nucleotide sites subject to mildly deleterious mutations. A complete lack of recombination in heterokaryotypes is assumed, as well as constancy of the frequency of the inversion over space and time. It is shown that a significantly higher mutational load will develop for the less frequent arrangement. A selective advantage to heterokaryotypes is only expected when the two alternative arrangements are nearly equal in frequency, so that their mutational loads are very similar in size. The effects of some Drosophila pseudoobscura polymorphic inversions on fitness traits seem to be too large to be explained by this process, although it may contribute to some of the observed effects. Several population genomic statistics can provide evidence for signatures of a reduced efficacy of selection associated with the rarer of two arrangements, but there is currently little published data that are relevant to the theoretical predictions.

Extensive haplotype diversity in a butterfly colour pattern supergene is fuelled by incomplete recombination suppression

“…It has also been suggested that load may promote polymorphism through associative overdominance, in which heterokaryotypes carrying different sets of deleterious recessive alleles have increased fitness relative to homokaryotypes due to masking of the deleterious recessives [23]. While examples of heterokaryotype advantage are known [24], it is difficult to prove that associative overdominance is the cause, especially given that the conditions under which it is likely to evolve are highly restrictive [25]. In D. chrysippus, there is no compelling evidence for heterozygote advantage: the three most common haplotype groups each occur in large regions of monomorphism, and broad clines suggest that polymorphism in the hybrid zone reflects a balance between selection (local adaptation) and extensive dispersal [37] rather than heterokaryotype advantage.…”

“…The fitness consequences of a supergene could also change if selective pressures change over time or across space, potentially limiting the value of a supergene in a changing environment or during dispersal into a new environment [22]. Even in a stable environment, inversion supergenes may be subject to accumulation of increased mutational load compared to the rest of the genome due to their reduced opportunities for recombination and reduced effective population size (Ne) (due to the effective subdivision of the population in that part of the genome) [23][24][25]. Some theoretical models suggest that this may lead to heterokaryotype advantage through sheltering of recessive deleterious mutations (associative overdominance) [23][24][25], or failure of locally adapted inversions to reach high frequency [26].…”