Multiple chromosomal inversions modulate continuous local adaptation along a steep thermal cline.

Chromosomal inversions are often implicated in divergence between distinct ecotypes, but their role in maintaining continuous adaptive divergence in complex traits remains poorly understood. Using quantitative and population genetics, transcriptomics, and artificial selection experiments, we demonstrate how inversions enable clinal adaptive divergence along a steep environmental gradient despite extensive gene flow in a widely distributed marine fish. We show that three inversions are associated with multiple adaptive traits and harbor the strongest signatures of divergent selection in the genome, implying a crucial adaptive role. These inversions exhibit contrasting selection signatures across latitudes, suggesting that they control distinct aspects of the same complex traits and facilitate adaptation in a modular way to different environmental pressures despite gene flow. Editor's summary: When chromosomal inversions link beneficial alleles, they can serve as potent targets of selection. However, determining which genes are of interest in inversions can be difficult. To identify the genetic basis of nine traits in the Atlantic silverside (Menidia menidia), Akopyan et al. examined the offspring of crosses between two geographically distant populations of these fish. They found that three inversions contributed to many of these traits, and both the traits and the inversions varied in frequency across populations despite active gene flow between them. Using gene expression data, the authors identified genes of interest in these regions that showed differential expression, including under different temperatures that would be experienced over the species' range. —Corinne Simonti INTRODUCTION: Adaptation to local environments is a hallmark of evolution, but gene flow between populations can erode adaptive differences. Resolving this classic evolutionary tension remains a major goal in biology that requires understanding the genetic basis of adaptation despite gene flow. Chromosomal inversions have emerged as important facilitators of this process by suppressing recombination and preserving beneficial allele combinations. Although a central role for inversions in mediating divergence between two ecotypes is well-established, how these inherently binary genetic elements might sustain continuous variation in multiple traits along environmental gradients remains a fundamental puzzle. RATIONALE: The Atlantic silverside (Menidia menidia) is a marine fish spanning Earth's steepest latitudinal gradient in coastal sea surface temperature and exhibits clinal genetic variation in multiple traits locally adapted across this environmental gradient. Many traits, such as growth rate, lipid storage, vertebral count, swimming speed, and metabolic rate gradually change with latitude, adaptations that enable populations to cope with decreasing length in growing season. We combine quantitative trait locus (QTL) mapping, range-wide population genomics, and experimental transcriptomic and lab-induced selection datasets to examine the genetic basis of local adaptation, assess genotype-phenotype links across independent contexts, and characterize patterns of selection and differentiation across the species' distribution. RESULTS: QTL mapping revealed that the strongest trait associations coincided with three large inversions (inv11, inv18, and inv24), each associated with multiple traits, suggesting they function as coadapted gene complexes. All three inversions were associated with growth and together explained ~40% of the trait variance. Inv24 was also significantly associated with body size in selection experiments and in wild populations, whereas inv11 and inv18 showed expected but nonsignificant trends, likely due to environmental variation and reduced genetic variation from artificial selection. Transcriptomic analyses revealed temperature-dependent differential expression of genes within inversions, enriched for functions related to growth and thermal stress. Genome-wide scans revealed that these inversions harbored the strongest signatures of divergent selection across the genome. All showed strong latitudinal clines with near fixation for opposite orientations at range extremes, with varying cline centers and widths, indicating different selection pressures and strengths. Genotype-environment associations and selective sweep analyses revealed that inversions respond to distinct environmental pressures and exhibit contrasting patterns of selection, with some showing consistent selection across populations and others displaying region-specific effects or distinct selection signatures across latitudes. The results show how multiple inversions provide a mechanism for modular adaptation across continuous environmental gradients. CONCLUSION: We demonstrate that multiple inversions maintain continuous adaptive trait variation along a steep environmental gradient. Three inversions show the strongest associations with adaptive traits and genome-wide signatures of divergent selection. These inversions exhibit contrasting selection patterns across latitudes and respond to distinct environmental pressures, suggesting that they control different aspects of complex traits in a modular fashion. This modular architecture enables fine-tuned responses to environmental heterogeneity despite gene flow, challenging the view of inversions as simple binary switches between ecotypes. Such flexibility may be particularly important for widely distributed species facing environmental changes as it could facilitate more rapid evolutionary responses. Inversions show distinct geographic patterns associated with multiple locally adapted traits in Atlantic silverside fish.: Three large chromosomal inversions (inv11, inv18, and inv24) are each associated with clinal variation in multiple adaptive traits—growth rate, body shape, lipid content, and vertebral number in Atlantic silversides. These inversions show distinct clinal patterns along the steepest coastal sea surface temperature gradient on Earth—the latitudinal gradient of the North American Atlantic coast. All three inversions show opposite haplotypes fixed (or nearly fixed) at the northern and southern range limits, but the latitude where haplotype frequencies shift differs for each inversion. [ABSTRACT FROM AUTHOR]