PLOS Genetics

Autor: Schwochow Thalmann, Doreen, Ring, Henrik, Sundström, Elisabeth, Cao, Xiaofang, Larsson, Mårten, Kerje, Susanne, Höglund, Andrey, Fogelholm, Jesper, Wright, Dominic, Jemth, Per, Hallböök, Finn, Bed’Hom, Bertrand, Dorshorst, Ben, Tixier-Boichard, Michèle, Andersson, Leif
Přispěvatelé: Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Department of Animal Breeding and Genetics, Institute of Agricultural Sciences for Southern Vietnam, Department of Neuroscience, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Department of Physics, Chemistry and Biology [Linköping] (IFM), Linköping University (LIU), Department of Animal and Poultry Sciences [Blacksburg] (APSC), Virginia Tech [Blacksburg], Department of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University System, Animal and Poultry Sciences
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: PLoS Genetics
PLoS Genetics, Public Library of Science, 2017, 13 (4), pp.1-22. ⟨10.1371/journal.pgen.1006665⟩
PLoS Genetics, Vol 13, Iss 4, p e1006665 (2017)
ISSN: 1553-7390
1553-7404
Popis: Sex-linked barring is a fascinating plumage pattern in chickens recently shown to be associated with two non-coding and two missense mutations affecting the ARF transcript at the CDKN2A tumor suppressor locus. It however remained a mystery whether all four mutations are indeed causative and how they contribute to the barring phenotype. Here, we show that Sex-linked barring is genetically heterogeneous, and that the mutations form three functionally different variant alleles. The B0 allele carries only the two non-coding changes and is associated with the most dilute barring pattern, whereas the B1 and B2 alleles carry both the two non-coding changes and one each of the two missense mutations causing the Sex-linked barring and Sex-linked dilution phenotypes, respectively. The data are consistent with evolution of alleles where the non-coding changes occurred first followed by the two missense mutations that resulted in a phenotype more appealing to humans. We show that one or both of the non-coding changes are cis-regulatory mutations causing a higher CDKN2A expression, whereas the missense mutations reduce the ability of ARF to interact with MDM2. Caspase assays for all genotypes revealed no apoptotic events and our results are consistent with a recent study indicating that the loss of melanocyte progenitors in Sex-linked barring in chicken is caused by premature differentiation and not apoptosis. Our results show that CDKN2A is a major locus driving the differentiation of avian melanocytes in a temporal and spatial manner.
Author summary Barring patterns on individual feathers are widespread phenomena in a number of wild bird species. Still, the genetic background and molecular mechanisms that give rise to barring remains poorly understood. Sex-linked barring is a striping pattern present on individual feathers in domestic chickens, which can be utilized as a model species to gain an understanding of the underlying ‘mode of action’ of biological pattern formation. Our findings suggest that regulatory mutations in the tumor suppressor gene CDKN2A first resulted in a primitive barring pattern and that two missense mutations in the same gene occurred later and independently, causing the more distinct barring pattern of extant chicken breeds. A plausible mechanism is that the altered expression of CDKN2A causes melanocyte progenitor cells to prematurely stop dividing and instead differentiate into pigment-producing cells. The temporary lack of melanocytes expresses itself as a white bar until the progenitor cells are replenished and pigment is produced to form a pigmented bar. It is remarkable that a good proportion of the world-wide production of animal protein is based on chicken that are carrying a functionally important missense mutation in the CDKN2A tumor suppressor gene.
Databáze: OpenAIRE
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