Large changes in detected selection signatures after a selection limit in mice bred for voluntary wheel-running behavior.

Autor: Hillis DA; Genetics, Genomics, and Bioinformatics Graduate Program, University of California, Riverside, California, United States of America., Yadgary L; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Weinstock GM; The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States of America.; Department of Genetics and Genome Science, University of Connecticut Health Center, Farmington, Connecticut, United States of America., de Villena FP; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Pomp D; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America., Garland T Jr; Department of Evolution, Ecology, and Organismal Biology, University of California, Riverside, California, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Aug 01; Vol. 19 (8), pp. e0306397. Date of Electronic Publication: 2024 Aug 01 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0306397
Abstrakt: In various organisms, sequencing of selectively bred lines at apparent selection limits has demonstrated that genetic variation can remain at many loci, implying that evolution at the genetic level may continue even if the population mean phenotype remains constant. We compared selection signatures at generations 22 and 61 of the "High Runner" mouse experiment, which includes 4 replicate lines bred for voluntary wheel-running behavior (HR) and 4 non-selected control (C) lines. Previously, we reported multiple regions of differentiation between the HR and C lines, based on whole-genome sequence data for 10 mice from each line at generation 61, which was >31 generations after selection limits had been reached in all HR lines. Here, we analyzed pooled sequencing data from ~20 mice for each of the 8 lines at generation 22, around when HR lines were reaching limits. Differentiation analyses of allele frequencies at ~4.4 million SNP loci used the regularized T-test and detected 258 differentiated regions with FDR = 0.01. Comparable analyses involving pooling generation 61 individual mouse genotypes into allele frequencies by line produced only 11 such regions, with almost no overlap among the largest and most statistically significant peaks between the two generations. These results implicate a sort of "genetic churn" that continues at loci relevant for running. Simulations indicate that loss of statistical power due to random genetic drift and sampling error are insufficient to explain the differences in selection signatures. The 13 differentiated regions at generation 22 with strict culling measures include 79 genes related to a wide variety of functions. Gene ontology identified pathways related to olfaction and vomeronasal pathways as being overrepresented, consistent with generation 61 analyses, despite those specific regions differing between generations. Genes Dspp and Rbm24 are also identified as potentially explaining known bone and skeletal muscle differences, respectively, between the linetypes.
Competing Interests: The authors have no competing interests.
(Copyright: © 2024 Hillis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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