Evolution of stickleback spines through independent cis-regulatory changes at HOXDB

Abstract

Understanding the mechanisms leading to new traits or additional features in organisms is a fundamental goal of evolutionary biology. We show that HOXDB regulatory changes have been used repeatedly in different fish genera to alter the length and number of the prominent dorsal spines used to classify stickleback species. In Gasterosteus aculeatus (typically ‘three-spine sticklebacks’), a variant HOXDB allele is genetically linked to shortening an existing spine and adding an additional spine. In Apeltes quadracus (typically ‘four-spine sticklebacks’), a variant HOXDB allele is associated with lengthening a spine and adding an additional spine in natural populations. The variant alleles alter the same non-coding enhancer region in the HOXDB locus but do so by diverse mechanisms, including single-nucleotide polymorphisms, deletions and transposable element insertions. The independent regulatory changes are linked to anterior expansion or contraction of HOXDB expression. We propose that associated changes in spine lengths and numbers are partial identity transformations in a repeating skeletal series that forms major defensive structures in fish. Our findings support the long-standing hypothesis that natural Hox gene variation underlies key patterning changes in wild populations and illustrate how different mutational mechanisms affecting the same region may produce opposite gene expression changes with similar phenotypic outcomes.

Whole-genome comparisons identify repeated regulatory changes underlying convergent appendage evolution in diverse fish lineages

“…Most previous examples of hotspot loci reused between distant phylogenetic groups have involved repeated amino acid changes in particular proteins (Courtier-Orgogozo et al ., 2020). PelA is one of a single-digit number of cis -regulatory regions now known to underlie naturally evolved convergent traits spanning intergeneric distances and above (Sagai et al ., 2004; Miller et al ., 2007; Guerreiro et al ., 2013; Kvon et al ., 2016; Wucherpfennig et al ., 2022).…”

The role of plastic and evolvedDNAmethylation in parallel adaptation of threespine stickleback (Gasterosteus aculeatus)

“…Two main alternatives have been proposed for the genetic basis of plasticity: (1) the plasticity is influenced by environmentally sensitive genes ( cis ‐acting) that have evolved as a byproduct of divergent natural selection (Via, 1993; Via et al, 1995) and (2) the mean and plasticity of a phenotype are influenced by separate ( trans ‐acting) genes (Scheiner, 1993; Signor & Nuzhdin, 2018). It has been suggested that both cis ‐ and trans ‐acting SNPs can play important roles in morphological (e.g., gill pigmentation, dorsal spine length and numbers, tooth numbers), gene expression, and methylation divergence between marine and freshwater ecotypes, but the relative contribution of cis ‐ versus trans ‐acting SNPs to ecotype divergence has been inconsistent between studies (Hart et al, 2018; Hu et al, 2021; Ishikawa et al, 2017; Reid et al, 2021; Verta & Jones, 2019; Wucherpfennig et al, 2022). In this study we found that although DMCs were much more likely to be associated with trans ‐acting SNPs than cis ‐acting SNPs, the relative proportion of trans ‐ vs. cis ‐ associations was in‐line with neutral expectations given the much greater number of trans ‐acting SNPs in the data set.…”

Inferring the evolution of reproductive isolation in a lineage of fossil threespine stickleback, Gasterosteus doryssus

“…The association between dorsal spine and pelvic phenotypes in this sample is not random (analysis below); having three dorsal spines was perfectly associated with having a full pelvis. In extant G. aculeatus, dorsal spine number and pelvic structure often do not map to the same genes [27][28][29][30]; but see [31]. Thus, if a similar genetic basis underlies trait divergence in both ancient G. doryssus and extant G. aculeatus (see Methods as well as [26,[31][32][33][34][35][36][37]), then any interbreeding among high-and low-armoured G. doryssus in the depositional environment should have produced a random association between the two armour traits.…”