An Ancestral Balanced Inversion Polymorphism Confers Global Adaptation

Abstract

Since the pioneering work of Dobzhansky in the 1930s and 1940s, many chromosomal inversions have been identified but how they contribute to adaptation remains poorly understood. In Drosophila melanogaster, the widespread inversion polymorphism In(3R)Payne underpins latitudinal clines in fitness traits on multiple continents. Here, we use single-individual whole-genome sequencing, transcriptomics and published sequencing data to study the population genomics of this inversion on four continents: in its ancestral African range and in derived populations in Europe, North America, and Australia. Our results confirm that this inversion originated in sub-Saharan Africa and subsequently became cosmopolitan; we observe marked monophyletic divergence of­­­­­­­ inverted and non-inverted karyotypes, with some substructure among inverted chromosomes between continents. Despite divergent evolution of this inversion since its out-of-Africa migration, derived non-African populations exhibit similar patterns of long-range linkage disequilibrium between the inversion breakpoints and major peaks of divergence in its center, consistent with balancing selection and suggesting that the inversion harbors alleles that are maintained by selection on several continents. Using RNA-seq we identify overlap between inversion-linked SNPs and loci that are differentially expressed between inverted and non-inverted chromosomes. Expression levels are higher for inverted chromosomes at low temperature, suggesting loss of buffering or compensatory plasticity and consistent with higher inversion frequency in warm climates. Our results suggest that this ancestrally tropical balanced polymorphism spread around the world and became latitudinally assorted along similar but independent climatic gradients, always being frequent in subtropical/tropical areas but rare or absent in temperate climates.

A cosmopolitan inversion facilitates seasonal adaptation in overwintering Drosophila

“…By showing that seasonal loci in In(2L)t are both young and old, our findings showcase that adaptive inversions that evolve by capturing old beneficial alleles often continue to accumulate adaptive mutation on existing inversion karyotypes ( Kirkpatrick and Barton 2006 ). This exemplifies instances of the action of ancient balancing selection across large spatial scales, and fine-tuning local adaptation within spatially structured populations (also see Kapun et al 2023 ). Furthermore, our work infers and experimentally validates the phenotypic effects of alternate alleles at a candidate locus linked to In(2L)t. Overall, this work is an example of evolution in action and provides new insights into the biology of adaptive cosmopolitan inversions.…”

“…Nonetheless, in a recent analysis of seasonal sampling across 2 continents, Machado et al (2021) identified the breakpoints of cosmopolitan inversions, particularly of the 10 Mb In(2L)t inversion, as regions enriched for loci that evolve by seasonal adaptive tracking. This is a notable finding given that adaptive loci that exist as chromosomal inversions have been extensively studied for decades and were among the first examples of loci underlying adaptations to a fluctuating environment ( Dobzhansky and Wright 1943 ; Charlesworth 2016 ; Kapun et al 2023 ).…”

The fitness consequences of genetic divergence between polymorphic gene arrangements

“…One of the best-studied D. melanogaster inversions is In(3R)P , with a frequency of 0.1 in populations in its ancestral range in Africa (Kapun and Flatt 2019), which are the most relevant populations for comparisons with the theoretical predictions. It is in the middle of the size range for polymorphic inversions in this species and covers approximately 8 Mb of sequence (Kapun et al 2023); This corresponds to approximately 1000 protein coding sequences, i.e., 10 6 nonsynonymous sites rather than the 10 5 selected sites illustrated in the figures. Functional noncoding sequences may also contribute to the mutational load, and these appear to be under weaker selective constraints than nonsynonymous mutations (Andolfatto 2005; Casillas et al 2007; Campos et al 2017).…”

The fitness consequences of genetic divergence between polymorphic gene arrangements

“…This has a frequency of 0.1 in populations in its ancestral range in Africa ( Kapun and Flatt 2019 ), which are the most relevant populations for comparisons with the theoretical predictions. It is in the middle of the size range for polymorphic inversions in this species, covering approximately 8 Mb of sequence ( Kapun et al . 2023 ).…”