@article{4cef7e231081461e9b7dc7e51c755f35,
title = "A mechanism for red coloration in vertebrates",
abstract = "Red coloration is a salient feature of the natural world. Many vertebrates produce red color by converting dietary yellow carotenoids into red ketocarotenoids via an unknown mechanism. Here, we show that two enzymes, cytochrome P450 2J19 (CYP2J19) and 3-hydroxybutyrate dehydrogenase 1-like (BDH1L), are sufficient to catalyze this conversion. In birds, both enzymes are expressed at the sites of ketocarotenoid biosynthesis (feather follicles and red cone photoreceptors), and genetic evidence implicates these enzymes in yellow/red color variation in feathers. In fish, the homologs of CYP2J19 and BDH1L are required for ketocarotenoid production, and we show that these enzymes are sufficient to produce ketocarotenoids in cell culture and when ectopically expressed in fish skin. Finally, we demonstrate that the red-cone-enriched tetratricopeptide repeat protein 39B (TTC39B) enhances ketocarotenoid production when co-expressed with CYP2J19 and BDH1L. The discovery of this mechanism of ketocarotenoid biosynthesis has major implications for understanding the evolution of color diversity in vertebrates.",
author = "Toomey, {Matthew B.} and Marques, {Cristiana I.} and Ara{\'u}jo, {Pedro M.} and Delai Huang and Siqiong Zhong and Yu Liu and Schreiner, {Gretchen D.} and Myers, {Connie A.} and Paulo Pereira and Sandra Afonso and Pedro Andrade and Gazda, {Ma{\l}gorzata A.} and Lopes, {Ricardo J.} and Ivan Viegas and Koch, {Rebecca E.} and Haynes, {Maureen E.} and Smith, {Dustin J.} and Yohey Ogawa and Daniel Murphy and Kopec, {Rachel E.} and Parichy, {David M.} and Miguel Carneiro and Corbo, {Joseph C.}",
note = "Funding Information: We thank members of the Corbo laboratory for feedback and discussion. We also thank Jocelyn Hudon, Charles Brown, Bruno Ara{\'u}jo, Miguel Monteiro, and V{\'i}tor Lopes for feather or blood samples. We thank Meadow Hansen, Desirae Gonzales, Brooke Joski, and Hannah Reeb for laboratory assistance, and we also thank Erica Lantelme and the Flow Cytometry Core in the Department of Pathology and Immunology at Washington University in St. Louis for FACS method development and services. The Genome Technology Access Core (GTAC) in the Department of Genetics at Washington University in St. Louis provided next-generation sequencing services. This work was supported by R01 EY030075 (to J.C.C.), NIH R35 GM122471 (to D.M.P.), NSF IOS 2037739 (to M.B.T.), as well as lab startup funds, Faculty Development Summer Fellowships, and the Undergraduate Research Challenge program at the University of Tulsa (to M.B.T.). Part of the carotenoid sample analysis was supported by USDA NIFA Hatch #W4122 (to R.E. Kopec) and NIH grant P30 CA016058 (to the Ohio State University and OSUCCC). This work was also supported by research contracts from the Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia (FCT) CEECINST/00014/2018/CP1512/CT0002 (to M.C.), 2020.01405.CEECIND/CP1601/CT0011 (to P.A.), and 2020.01494.CEECIND (to P.M.A.); by the European Research Council (ERC; to M.C.) under the European Union's Horizon 2020 research and innovation programme (grant agreement no. 101000504); by Portuguese national funds Transitory Norm contract (DL57/2016/CP1440/CT0006; to R.J.L.); and by research fellowships PD/BD/114042/2015 (to M.A.G.), SFRH/BD/147030/2019 (to C.I.M.), and PD/BD/128492/2017 (to P.P.) under the auspices of the Biodiversity, Genetics, and Evolution (BIODIV) PhD program. M.B.T. M.C. and J.C.C. conceived the project. M.B.T. D.J.S. M.E.H. M.C. C.I.M. P.M.A. P.P. S.A. P.A. M.A.G. R.J.L. I.V. S.Z. R.E. Kopec, R.E. Koch, D.H. D.M.P. Y.L. G.D.S. C.A.M. Y.O. D.M. and J.C.C. performed the experiments and/or analyzed the data. M.B.T. M.C. and J.C.C. supervised and administered the project. M.B.T. M.C. R.E. Kopec, D.M.P. and J.C.C. acquired funding for the project. M.B.T. M.C. and J.C.C. wrote the manuscript with input from all authors. The authors declare no competing interests. Funding Information: We thank members of the Corbo laboratory for feedback and discussion. We also thank Jocelyn Hudon, Charles Brown, Bruno Ara{\'u}jo, Miguel Monteiro, and V{\'i}tor Lopes for feather or blood samples. We thank Meadow Hansen, Desirae Gonzales, Brooke Joski, and Hannah Reeb for laboratory assistance, and we also thank Erica Lantelme and the Flow Cytometry Core in the Department of Pathology and Immunology at Washington University in St. Louis for FACS method development and services. The Genome Technology Access Core (GTAC) in the Department of Genetics at Washington University in St. Louis provided next-generation sequencing services. This work was supported by R01 EY030075 (to J.C.C.), NIH R35 GM122471 (to D.M.P.), NSF IOS 2037739 (to M.B.T.), as well as lab startup funds, Faculty Development Summer Fellowships, and the Undergraduate Research Challenge program at the University of Tulsa (to M.B.T.). Part of the carotenoid sample analysis was supported by USDA NIFA Hatch # W4122 (to R.E. Kopec) and NIH grant P30 CA016058 (to the Ohio State University and OSUCCC). This work was also supported by research contracts from the Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia (FCT) CEECINST/00014/2018/CP1512/CT0002 (to M.C.), 2020.01405.CEECIND/CP1601/CT0011 (to P.A.), and 2020.01494.CEECIND (to P.M.A.); by the European Research Council (ERC; to M.C.) under the European Union{\textquoteright}s Horizon 2020 research and innovation programme (grant agreement no. 101000504 ); by Portuguese national funds Transitory Norm contract ( DL57/2016/CP1440/CT0006 ; to R.J.L.); and by research fellowships PD/BD/114042/2015 (to M.A.G.), SFRH/BD/147030/2019 (to C.I.M.), and PD/BD/128492/2017 (to P.P.) under the auspices of the Biodiversity, Genetics, and Evolution (BIODIV) PhD program. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = oct,
day = "10",
doi = "10.1016/j.cub.2022.08.013",
language = "English",
volume = "32",
pages = "4201--4214.e12",
journal = "Current Biology",
issn = "0960-9822",
number = "19",
}