Mutation load at a mimicry supergene sheds new light on the evolution of inversion polymorphisms

Abstract

Chromosomal inversions are ubiquitous in genomes and often coordinate complex phenotypes, such as the covariation of behavior and morphology in many birds, fishes, insects or mammals [1][2][3][4][5][6][7][8][9][10][11] . However, why and how inversions become associated with polymorphic traits remains obscure. Here we show that despite a strong selective advantage when they form, inversions accumulate recessive deleterious mutations that generate frequency-dependent selection and promote their maintenance at intermediate frequency. Combining genomics and in vivo fitness analyses in a model butterfly for wing-pattern polymorphism, Heliconius numata, we reveal that three ecologically advantageous inversions have built up a heavy mutational load from the sequential accumulation of deleterious mutations and transposable elements. Inversions associate with sharply reduced viability when homozygous, which prevent them from replacing ancestral chromosome arrangements. Our results suggest that other complex polymorphisms, rather than representing adaptations to competing ecological optima, could evolve because chromosomal rearrangements are intrinsically prone to carrying recessive harmful mutations.Many organisms display concerted variation in their phenotypic traits. Consistent association of multiple phenotypic features, combining differences in behavior, morphology and physiology, may result in so-called syndromes, or complex traits with clear adaptive significance. This coordination is often controlled by chromosomal rearrangements. Examples include dimorphic social organization in several ant species 7 , color displays and mating behaviors in many birds and butterflies [3][4][5][6]12 , dimorphic flower morphology in plants 13 , as well as the extreme cases provided by sexual dimorphism in numerous animals. Why and how these structurally-delimited complex polymorphisms arise is a long-standing puzzle in biology 11,14-17 . The so-called supergenes controlling the coordination of the multiple phenotypic features are characterized by suppression of recombination, often through polymorphic chromosomal rearrangements, which preserve alternative combinations of alleles at linked genes 4,7,11,13 . The encoded multi-feature phenotypes are often assumed to reflect the existence of multiple, distinct adaptive optima, and their maintenance in polymorphisms to result from antagonistic ecological factors such as differential survival or mating success 8,12,18,19 . Yet why and how polymorphic

The Genomic Architecture and Evolutionary Fates of Supergenes

“…Furthermore, Jay et al (2021) found that the inversions P 1 , P 2 , and P 3 show an elevated proportion of nonsynonymous relative to synonymous polymorphism ( p N /p S ) in comparison to genome-wide estimates and estimates for noninverted homologous regions. Interestingly, experiments have shown strongly reduced larval survivorship of individuals homozygous for the same derived inverted arrangement at the supergene ( Jay et al 2021 ). Thus, the accumulation of mutations in H. numata may also contribute to maintenance of the supergene polymorphism, as heterozygotes for alternative recessive deleterious mutations are fitter than homozygotes.…”

“…Initial genetic work determined that the complex mimicry polymorphism in H. numata is governed by the P locus, a genomic region that harbors a set of genomic rearrangements that guarantee the joint inheritance of loci involved in color patterning due to the presence of a 400-kb inversion (P 1 ) containing 21 genes ( Joron et al 2006 , 2011 ; Jay et al 2021 ). The P 1 inversion includes cortex , a gene involved in pigmentation patterning in many butterfly lineages ( Nadeau et al 2016 ).…”

“…This result suggests that introgression of the inverted haplotype contributed to the initial establishment of the supergene, without the evolution of close linkage in response to interactions among loci. Once established in H. numata , the P 1 -carrying allele not only spread but also diversified through the occurrence of two sequential chromosomal rearrangements known as P 2 (200 kb, 15 genes) and P 3 (1,150 kb, 71 genes) ( Jay et al 2018 , 2021 ) ( fig. 2 C ).…”

“…Several lines of evidence suggest that purifying selection may be weaker in the inverted arrangement compared with the standard arrangement of the P locus. For instance, the inverted regions have experienced a recent accumulation of transposable elements (TEs), which contributed to an approximately 9% size increase compared with the noninverted regions on the ancestral Hn0 arrangement ( Jay et al 2021 ). Furthermore, Jay et al (2021) found that the inversions P 1 , P 2 , and P 3 show an elevated proportion of nonsynonymous relative to synonymous polymorphism ( p N /p S ) in comparison to genome-wide estimates and estimates for noninverted homologous regions.…”

“…For instance, the inverted regions have experienced a recent accumulation of transposable elements (TEs), which contributed to an approximately 9% size increase compared with the noninverted regions on the ancestral Hn0 arrangement ( Jay et al 2021 ). Furthermore, Jay et al (2021) found that the inversions P 1 , P 2 , and P 3 show an elevated proportion of nonsynonymous relative to synonymous polymorphism ( p N /p S ) in comparison to genome-wide estimates and estimates for noninverted homologous regions. Interestingly, experiments have shown strongly reduced larval survivorship of individuals homozygous for the same derived inverted arrangement at the supergene ( Jay et al 2021 ).…”