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Accession IconSRP188258

A beneficial genomic rearrangement creates multiple versions of calcipressin in C. elegans

Organism Icon Caenorhabditis elegans
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Technology Badge IconNextSeq 500

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Gene duplication is a major source of genetic novelty and evolutionary adaptation, providing a molecular substrate that can generate biological complexity and diversity (Ohno 1967, Taylor and Raes 2004). Despite an abundance of genomic evidence from extant organisms to the importance of gene duplication, consensus about how they arise and fix in a species is lacking (Innan and Kondrashov 2010). In the process of studying the adaptation of laboratory strains of C. elegans to new food sources, we identified a recombinant inbred line (RIL) with higher relative fitness and hyperactive exploration behavior compared to either parental strain. Using bulked segregant analysis and short read resequencing, we identified a de novo beneficial, complex rearrangement of the rcan-1 gene, which we resolved into five new unique tandem inversion/duplications using Oxford Nanopore long-read sequencing. rcan-1 encodes an ortholog to the human RCAN1/DSCR1 gene, which has been implicated as a causal gene for Down syndrome (Fuentes, Genesca et al. 2000). The genomic rearrangement in rcan-1 results in two complete and two truncated versions of the rcan-1 coding region, with a variety of modified promoter and 3' regions, resulting in reduced whole-body expression. This rearrangement does not phenocopy a loss-of-function allele, indicating the rearrangement was necessary for the fitness gains. Our results demonstrate that adaptation can occur through unexpectedly complex genetic changes that can provide the molecular substrate for future evolutionary change.
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