A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken.
The biochemical pathway regulating the synthesis of yellow/red pheomelanin is less well characterized than the synthesis of black/brown eumelanin. Inhibitor of gold (IG phenotype) is a plumage colour variant in chicken that provides an opportunity to further explore this pathway since the recessive...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-04-01
|
| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1010724 |
| _version_ | 1797832274656362496 |
|---|---|
| author | Huijuan Bi Jonas Tranell Dawn C Harper Weifeng Lin Jingyi Li Anders R Hellström Mårten Larsson Carl-Johan Rubin Chao Wang Shumaila Sayyab Susanne Kerje Bertrand Bed'hom David Gourichon Shosuke Ito Kazumasa Wakamatsu Michèle Tixier-Boichard Michael S Marks Daniel Globisch Leif Andersson |
| author_facet | Huijuan Bi Jonas Tranell Dawn C Harper Weifeng Lin Jingyi Li Anders R Hellström Mårten Larsson Carl-Johan Rubin Chao Wang Shumaila Sayyab Susanne Kerje Bertrand Bed'hom David Gourichon Shosuke Ito Kazumasa Wakamatsu Michèle Tixier-Boichard Michael S Marks Daniel Globisch Leif Andersson |
| author_sort | Huijuan Bi |
| collection | DOAJ |
| description | The biochemical pathway regulating the synthesis of yellow/red pheomelanin is less well characterized than the synthesis of black/brown eumelanin. Inhibitor of gold (IG phenotype) is a plumage colour variant in chicken that provides an opportunity to further explore this pathway since the recessive allele (IG) at this locus is associated with a defect in the production of pheomelanin. IG/IG homozygotes display a marked dilution of red pheomelanin pigmentation, whilst black pigmentation (eumelanin) is only slightly affected. Here we show that a 2-base pair insertion (frame-shift mutation) in the 5th exon of the Catechol-O-methyltransferase containing domain 1 gene (COMTD1), expected to cause a complete or partial loss-of-function of the COMTD1 enzyme, shows complete concordance with the IG phenotype within and across breeds. We show that the COMTD1 protein is localized to mitochondria in pigment cells. Knockout of Comtd1 in a mouse melanocytic cell line results in a reduction in pheomelanin metabolites and significant alterations in metabolites of glutamate/glutathione, riboflavin, and the tricarboxylic acid cycle. Furthermore, COMTD1 overexpression enhanced cellular proliferation following chemical-induced transfection, a potential inducer of oxidative stress. These observations suggest that COMTD1 plays a protective role for melanocytes against oxidative stress and that this supports their ability to produce pheomelanin. |
| first_indexed | 2024-04-09T14:05:11Z |
| format | Article |
| id | doaj.art-26f9c941897443029cc17bdb2ccab876 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-04-09T14:05:11Z |
| publishDate | 2023-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-26f9c941897443029cc17bdb2ccab8762023-05-07T05:31:49ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042023-04-01194e101072410.1371/journal.pgen.1010724A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken.Huijuan BiJonas TranellDawn C HarperWeifeng LinJingyi LiAnders R HellströmMårten LarssonCarl-Johan RubinChao WangShumaila SayyabSusanne KerjeBertrand Bed'homDavid GourichonShosuke ItoKazumasa WakamatsuMichèle Tixier-BoichardMichael S MarksDaniel GlobischLeif AnderssonThe biochemical pathway regulating the synthesis of yellow/red pheomelanin is less well characterized than the synthesis of black/brown eumelanin. Inhibitor of gold (IG phenotype) is a plumage colour variant in chicken that provides an opportunity to further explore this pathway since the recessive allele (IG) at this locus is associated with a defect in the production of pheomelanin. IG/IG homozygotes display a marked dilution of red pheomelanin pigmentation, whilst black pigmentation (eumelanin) is only slightly affected. Here we show that a 2-base pair insertion (frame-shift mutation) in the 5th exon of the Catechol-O-methyltransferase containing domain 1 gene (COMTD1), expected to cause a complete or partial loss-of-function of the COMTD1 enzyme, shows complete concordance with the IG phenotype within and across breeds. We show that the COMTD1 protein is localized to mitochondria in pigment cells. Knockout of Comtd1 in a mouse melanocytic cell line results in a reduction in pheomelanin metabolites and significant alterations in metabolites of glutamate/glutathione, riboflavin, and the tricarboxylic acid cycle. Furthermore, COMTD1 overexpression enhanced cellular proliferation following chemical-induced transfection, a potential inducer of oxidative stress. These observations suggest that COMTD1 plays a protective role for melanocytes against oxidative stress and that this supports their ability to produce pheomelanin.https://doi.org/10.1371/journal.pgen.1010724 |
| spellingShingle | Huijuan Bi Jonas Tranell Dawn C Harper Weifeng Lin Jingyi Li Anders R Hellström Mårten Larsson Carl-Johan Rubin Chao Wang Shumaila Sayyab Susanne Kerje Bertrand Bed'hom David Gourichon Shosuke Ito Kazumasa Wakamatsu Michèle Tixier-Boichard Michael S Marks Daniel Globisch Leif Andersson A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken. PLoS Genetics |
| title | A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken. |
| title_full | A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken. |
| title_fullStr | A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken. |
| title_full_unstemmed | A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken. |
| title_short | A frame-shift mutation in COMTD1 is associated with impaired pheomelanin pigmentation in chicken. |
| title_sort | frame shift mutation in comtd1 is associated with impaired pheomelanin pigmentation in chicken |
| url | https://doi.org/10.1371/journal.pgen.1010724 |
| work_keys_str_mv | AT huijuanbi aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT jonastranell aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT dawncharper aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT weifenglin aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT jingyili aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT andersrhellstrom aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT martenlarsson aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT carljohanrubin aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT chaowang aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT shumailasayyab aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT susannekerje aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT bertrandbedhom aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT davidgourichon aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT shosukeito aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT kazumasawakamatsu aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT micheletixierboichard aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT michaelsmarks aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT danielglobisch aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT leifandersson aframeshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT huijuanbi frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT jonastranell frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT dawncharper frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT weifenglin frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT jingyili frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT andersrhellstrom frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT martenlarsson frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT carljohanrubin frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT chaowang frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT shumailasayyab frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT susannekerje frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT bertrandbedhom frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT davidgourichon frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT shosukeito frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT kazumasawakamatsu frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT micheletixierboichard frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT michaelsmarks frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT danielglobisch frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken AT leifandersson frameshiftmutationincomtd1isassociatedwithimpairedpheomelaninpigmentationinchicken |