A spontaneous complex structural variant in rcan-1 increases exploratory behavior and laboratory fitness of Caenorhabditis elegans

Autoři: Yuehui Zhao aff001;  Lijiang Long aff001;  Jason Wan aff003;  Shweta Biliya aff001;  Shannon C. Brady aff004;  Daehan Lee aff004;  Akinade Ojemakinde aff001;  Erik C. Andersen aff004;  Fredrik O. Vannberg aff001;  Hang Lu aff005;  Patrick T. McGrath aff001
Působiště autorů: School of Biological Sciences, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff001;  Interdisciplinary Graduate Program in Quantitative Biosciences, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff002;  The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, United States of America aff003;  Department of Molecular Biosciences, Northwestern University, Evanston, Illinois, United States of America aff004;  Parker H. Petit Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff005;  School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff006;  School of Physics, Georgia Institute of Technology, Atlanta, Georgia, United States of America aff007
Vyšlo v časopise: A spontaneous complex structural variant in rcan-1 increases exploratory behavior and laboratory fitness of Caenorhabditis elegans. PLoS Genet 16(2): e32767. doi:10.1371/journal.pgen.1008606
Kategorie: Research Article
doi: 10.1371/journal.pgen.1008606


Over long evolutionary timescales, major changes to the copy number, function, and genomic organization of genes occur, however, our understanding of the individual mutational events responsible for these changes is lacking. In this report, we study the genetic basis of adaptation of two strains of C. elegans to laboratory food sources using competition experiments on a panel of 89 recombinant inbred lines (RIL). Unexpectedly, we identified a single RIL with higher relative fitness than either of the parental strains. This strain also displayed a novel behavioral phenotype, resulting in higher propensity to explore bacterial lawns. Using bulk-segregant analysis and short-read resequencing of this RIL, we mapped the change in exploration behavior to a spontaneous, complex rearrangement of the rcan-1 gene that occurred during construction of the RIL panel. We resolved this rearrangement into five unique tandem inversion/duplications using Oxford Nanopore long-read sequencing. rcan-1 encodes an ortholog to human RCAN1/DSCR1 calcipressin gene, which has been implicated as a causal gene for Down syndrome. The genomic rearrangement in rcan-1 creates two complete and two truncated versions of the rcan-1 coding region, with a variety of modified 5’ and 3’ non-coding regions. While most copy-number variations (CNVs) are thought to act by increasing expression of duplicated genes, these changes to rcan-1 ultimately result in the reduction of its whole-body expression due to changes in the upstream regions. By backcrossing this rearrangement into a common genetic background to create a near isogenic line (NIL), we demonstrate that both the competitive advantage and exploration behavioral changes are linked to this complex genetic variant. This NIL strain does not phenocopy a strain containing an rcan-1 loss-of-function allele, which suggests that the residual expression of rcan-1 is necessary for its fitness effects. Our results demonstrate how colonization of new environments, such as those encountered in the laboratory, can create evolutionary pressure to modify gene function. This evolutionary mismatch can be resolved by an unexpectedly complex genetic change that simultaneously duplicates and diversifies a gene into two uniquely regulated genes. Our work shows how complex rearrangements can act to modify gene expression in ways besides increased gene dosage.

Klíčová slova:

Behavior – Caenorhabditis elegans – Evolutionary genetics – Gene expression – Genome complexity – Inbred strains – Polymerase chain reaction – Sequence alignment


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