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Nat Genet. 2017 Jan;49(1):119-124. doi: 10.1038/ng.3732. Epub 2016 Dec 5.

The genome and transcriptome of Japanese flounder provide insights into flatfish asymmetry.

Shao C1,2, Bao B3, Xie Z4, Chen X3, Li B4, Jia X1,2, Yao Q4, Ortí G5, Li W4, Li X1,2, Hamre K6,7, Xu J3, Wang L1,2, Chen F4, Tian Y1,2, Schreiber AM8, Wang N1,2, Wei F3, Zhang J4, Dong Z1,2, Gao L3, Gai J3, Sakamoto T9, Mo S1,2, Chen W3, Shi Q4, Li H3, Xiu Y1,2, Li Y1,2, Xu W1,2, Shi Z3, Zhang G4, Power DM10,11, Wang Q1,2, Schartl M12,13, Chen S1,2.

Author information

Yellow Sea Fisheries Research Institute, CAFS, Key Laboratory for Sustainable Development of Marine Fisheries, Ministry of Agriculture, Qingdao, China.
Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China.
The Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of Education, Shanghai, China.
BGI-Shenzhen, Shenzhen, China.
Department of Biological Sciences, George Washington University, Washington, DC, USA.
National Institute of Nutrition and Seafood Research (NIFES), Bergen, Norway.
Department of Biology, University of Bergen, Bergen, Norway.
St. Lawrence University, Biology Department, Canton, New York, USA.
Graduate School of Marine Science and Technology, Tokyo University of Marine Science and Technology, Tokyo, Japan.
Centro de Ciências do Mar (CCMAR), Comparative Endocrinology and Integrative Biology, Universidade do Algarve, Faro, Portugal.
College of Fisheries and Life Science, Shanghai Ocean University, Ministry of Education, Shanghai, China.
Physiologische Chemie, University of Würzburg, Biozentrum, Am Hubland, and Comprehensive Cancer Center Mainfranken, University Clinic Würzburg, Würzburg, Germany.
Institute for Advanced Studies, Texas A&M University, College Station, Texas, USA.


Flatfish have the most extreme asymmetric body morphology of vertebrates. During metamorphosis, one eye migrates to the contralateral side of the skull, and this migration is accompanied by extensive craniofacial transformations and simultaneous development of lopsided body pigmentation. The evolution of this developmental and physiological innovation remains enigmatic. Comparative genomics of two flatfish and transcriptomic analyses during metamorphosis point to a role for thyroid hormone and retinoic acid signaling, as well as phototransduction pathways. We demonstrate that retinoic acid is critical in establishing asymmetric pigmentation and, via cross-talk with thyroid hormones, in modulating eye migration. The unexpected expression of the visual opsins from the phototransduction pathway in the skin translates illumination differences and generates retinoic acid gradients that underlie the generation of asymmetry. Identifying the genetic underpinning of this unique developmental process answers long-standing questions about the evolutionary origin of asymmetry, but it also provides insight into the mechanisms that control body shape in vertebrates.

[Indexed for MEDLINE]

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