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

• Published in: Nature ecology & evolution Vol. 6; no. 10; pp. 1537 - 1552
• Main Authors: Wucherpfennig, Julia I., Howes, Timothy R., Au, Jessica N., Au, Eric H., Roberts Kingman, Garrett A., Brady, Shannon D., Herbert, Amy L., Reimchen, Thomas E., Bell, Michael A., Lowe, Craig B., Dalziel, Anne C., Kingsley, David M.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2022; Nature Publishing Group
• Subjects: 38; 38/23; 38/77; 38/91; 45; 45/22; 45/90; 59; 631/181/2474; 631/208/182; 64; Alleles; Animals; Biological and Physical Anthropology; Biomedical and Life Sciences; Developmental biology; DNA Transposable Elements; Ecology; Evolutionary Biology; Fish; Gene expression; Genes, Homeobox; HOX gene; Life Sciences; Natural populations; Nucleotides; Paleontology; Phenotype; Population genetics; Populations; Single-nucleotide polymorphism; Smegmamorpha - genetics; Species classification; Spines; Transposons; Zoology
• ISSN: 2397-334X; 2397-334X
• DOI: 10.1038/s41559-022-01855-3

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. Differences in a non-coding enhancer region of the HOXDB locus underlie the differences between stickleback species in dorsal spine length and number. These differences include single-nucleotide polymorphisms, deletions and transposable element insertions.