Rabbits display a wide range of coat colors, with yellow being a particular phenotype that aids in exploring the molecular mechanisms of coat pigmentation. The Fujian yellow (FJY) rabbit, as China's only indigenous breed with a yellow coat, serves as a valuable genetic resource. Fujian yellow rabbits have predominantly yellow fur, with a diluted white hue on the distal limbs and tail. However, the genetic mechanism underlying yellow coat color remains unclear. To address this, we conducted selection signature analysis to identify candidate genes and potential casual mutations underlying the yellow phenotype in rabbits. Utilizing whole-genome resequencing, a total of 22 486 177 high-quality SNPs were identified from 30 individuals belonging to three Chinese indigenous rabbit breeds featured with yellow or non-yellow phenotype. The results revealed that the ASIP gene on chromosome 4 and the SNAI2 gene on chromosome 3 were under strong selection pressure, both of which play pivotal roles in determining coat color phenotypes. The ASIP gene is involved in melanogenesis across various livestock species, while the SNAI2 gene is linked to hypopigmentation in the distal regions such as the limbs and tail. We further identified two SNP variants, g.23870943C>T in the fourth intron of the ASIP gene, which is closely associated with the yellow phenotype, and g.73725380A>G downstream of the SNAI2 gene, probably contributing to the white shading in Fujian yellow rabbits' limb and tail regions. These variants are key determinants in the development of the yellow coat color in rabbits. These findings advance the understanding of coat color pigmentation in domestic animals.
Bannasch, D.L., Kaelin, C.B., Letko, A., Loechel, R., Hug, P., Jagannathan, V. et al. (2021) Dog colour patterns explained by modular promoters of ancient canid origin. Nature Ecology & Evolution, 5, 1415–1423.
Beauvois, H., De Citres, C.D., Gache, V. & Abitbol, M. (2021) Siberian cats help in solving part of the mystery surrounding golden cats. Animal Genetics, 52, 482–491.
Bolger, A.M., Lohse, M. & Usadel, B. (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics, 30, 2114–2120.
Chavez, D.E., Gronau, I., Flains, T., Kliver, S., Koepfli, K.P. & Wayne, R.K. (2019) Comparative genomics provides new insights into the remarkable adaptations of the African wild dog (Lycaon pictus). Scientific Reports, 9, 14.
Danecek, P., Auton, A., Abecasis, G., Albers, C.A., Banks, E., Depristo, M.A. et al. (2011) The variant call format and VCFtools. Bioinformatics, 27, 2156–2158.
Fontanesi, L., Forestier, L., Allain, D., Scotti, E., Beretti, F., Deretz‐Picoulet, S. et al. (2010) Characterization of the rabbit agouti signaling protein (ASIP) gene: transcripts and phylogenetic analyses and identification of the causative mutation of the nonagouti black coat colour. Genomics, 95, 166–175.
Guo, J.Z., Tao, H.X., Li, P.F., Li, L., Zhong, T., Wang, L.J. et al. (2018) Whole‐genome sequencing reveals selection signatures associated with important traits in six goat breeds. Scientific Reports, 8(1), 10405.
Gurao, A., Vasisth, R., Singh, R., Dige, M.S., Vohra, V., Mukesh, M. et al. (2022) Identification of differential methylome signatures of white pigmented skin patches in Nili Ravi buffalo of India. Environmental and Molecular Mutagenesis, 63, 408–417.
Kaelin, C.B., Xu, X., Hong, L.Z., David, V.A., Mcgowan, K.A., Schmidt‐Küntzel, A. et al. (2012) Specifying and sustaining pigmentation patterns in domestic and wild cats. Science, 337, 1536–1541.
Letko, A., Ammann, B., Jagannathan, V., Henkel, J., Leuthard, F., Schelling, C. et al. (2020) A deletion spanning the promoter and first exon of the hair cycle‐specific ASIP transcript isoform in black and tan rabbits. Animal Genetics, 51, 137–140.
Li, F. (2016) Rabbit production science. China: China Agricultural Press.
Li, H. & Durbin, R. (2009) Fast and accurate short read alignment with Burrows‐Wheeler transform. Bioinformatics, 25, 1754–1760.
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N. et al. (2009) The sequence alignment/map format and SAMtools. Bioinformatics, 25, 2078–2079.
Mckenna, A., Hanna, M., Banks, E., Sivachenko, A., Cibulskis, K., Kernytsky, A. et al. (2010) The genome analysis toolkit: a MapReduce framework for analyzing next‐generation DNA sequencing data. Genome Research, 20, 1297–1303.
Michaud, E.J., Bultman, S.J., Klebig, M.L., Vanvugt, M.J., Stubbs, L.J., Russell, L.B. et al. (1994) A molecular model for the genetic and phenotypic characteristics of the mouse lethal yellow (Ay) mutation. Proceedings of the National Academy of Sciences of the United States of America, 91, 2562–2566.
Miller, M.W., Duhl, D.M.J., Vrieling, H., Cordes, S.P., Ollmann, M.M., Winkes, B.M. et al. (1993) Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation. Genes & Development, 7, 454–467.
Norris, B.J. & Whan, V.A. (2008) A gene duplication affecting expression of the ovine ASIP gene is responsible for white and black sheep. Genome Research, 18, 1282–1293.
Ollmann, M.M., Lamoreux, M.L., Wilson, B.D. & Barsh, G.S. (1997) Interaction of Agouti protein with the melanocortin 1 receptor in vitro and in vivo. Genes & Development, 12, 316–330.
Pérez‐Losada, J., Sánchez‐Martín, M., Rodríguez‐García, A., Sánchez, M.L., Orfao, A., Flores, T. et al. (2002) Zinc‐finger transcription factor Slug contributes to the function of the stem cell factor c‐kit signaling pathway. Blood, 100, 1274–1286.
Pingault, V., Ente, D., Dastot‐Le Moal, F., Goossens, M., Marlin, S. & Bondurand, N. (2010) Review and update of mutations causing Waardenburg syndrome. Human Mutation, 31, 391–406.
Purcell, S., Neale, B., Todd‐Brown, K., Thomas, L., Ferreira, M.A.R., Bender, D. et al. (2007) PLINK: a tool set for whole‐genome association and population‐based linkage analyses. American Journal of Human Genetics, 81, 559–575.
Quinlan, A.R. & Hall, I.M. (2010) BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics, 26, 841–842.
Robic, A., Morisson, M., Leroux, S., Gourichon, D., Vignal, A., Thebault, N. et al. (2019) Two new structural mutations in the 5′ region of the ASIP gene cause diluted feather color phenotypes in Japanese quail. Genetics Selection Evolution, 51, 12.
Sánchez‐Martín, M., Rodríguez‐García, A., Pérez‐Losada, J., Sagrera, A., Read, A.P. & Sánchez‐García, I. (2002) SLUG (SNAI2) deletions in patients with Waardenburg disease. Human Molecular Genetics, 11, 3231–3236.
Sani, M.B., Harofte, J.Z., Banabazi, M.H., Faraz, A., Esmaeilkhanian, S., Naderi, A.S. et al. (2022) Identification of candidate genes for pigmentation in camels using genotyping‐by‐sequencing. Animals, 12(9), 1095.
Schmutz, S.M. & Berryere, T.G. (2007) Genes affecting coat colour and pattern in domestic dogs: a review. Animal Genetics, 38, 539–549.
Tribulo, C., Aybar, M.J., Sanchez, S.S. & Mayor, R. (2004) A balance between the anti‐apoptotic activity of Slug and the apoptotic activity of msx1 is required for the proper development of the neural crest. Developmental Biology, 275, 325–342.
Zhou, W., Gross, K.M. & Kuperwasser, C. (2019) Molecular regulation of Snai2 in development and disease. Journal of Cell Science, 132(23), jcs235127. Available from: https://doi.org/10.1242/jcs.235127