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The key role of myostatin b in somatic growth in fishes derived from distant hybridization

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Abstract

The basic mechanism of heterosis has not been systematically and completely characterized. In previous studies, we obtained three economically important fishes that exhibit rapid growth, WR (WCC ♀ × RCC ♂), WR-II (WR ♀ × WCC ♂), and WR-III (WR-II ♀ × 4nAU ♂), through distant hybridization. However, the mechanism underlying this rapid growth remains unclear. In this study, we found that WR, WR-II, and WR-III showed muscle hypertrophy and higher muscle protein and fat contents compared with their parent species (RCC and WCC). Candidate genes responsible for this rapid growth were then obtained through an analysis of 12 muscle transcriptomes. Notably, the mRNA level of mstnb (myostatin b), which is a negative regulator of myogenesis, was significantly reduced in WR, WR-II, and WR-III compared with the parent species. To verify the function of mstnb, a mstnb-deficient mutant RCC line was generated using the CRISPR-Cas9 technique. The average body weight of mstnb-deficient RCC at 12 months of age was significantly increased by 29.57% compared with that in wild-type siblings. Moreover, the area and number of muscle fibers were significantly increased in mstnb-deficient RCC, indicating hypertrophy and hyperplasia. Furthermore, the muscle protein and fat contents were significantly increased in mstnb-deficient RCC. The molecular regulatory mechanism of mstnb was then revealed by transcription profiling, which showed that genes related to myogenesis (myod, myog, and myf5), protein synthesis (PI3K-AKT-mTOR), and lipogenesis (pparγ and fabp3) were highly activated in hybrid fishes and mstnb-deficient RCC. This study revealed that low expression or deficiency of mstnb regulates somatic growth by promoting myogenesis, protein synthesis, and lipogenesis in hybrid fishes and mstnb-deficient RCC, which provides evidence for the molecular mechanism of heterosis via distant hybridization.

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Data availability statement

The complete clean reads for these libraries have been uploaded to the NCBI Sequence Read Archive site (http://www.ncbi.nlm.nih.gov/sra/; Accession Nos. SRR25395549, SRR25395550, SRR25395551, SRR25395552, SRR25395553, SRR25395554, SRR25395555, SRR25395556, SRR25395557, SRR25395558, SRR25395559, and SRR25395560).

References

  • Argue, B.J., Kuhlers, D.L., Liu, Z., and Dunham, R.A. (2014). Growth of channel catfish (Ictalurus punctatus), blue catfish (I. furcatus), and their F1, F2, F3, and F1 reciprocal backcross hybrids in earthen ponds. J Anim Sci 92, 4297–4305.

    Article  CAS  PubMed  Google Scholar 

  • Bartley, D.M., Rana, K., and Immink, A.J. (2000). The use of interspecific hybrids in aquaculture and fisheries. reviews in fish. Rev Fish Biol Fish 10, 325–337.

    Article  Google Scholar 

  • Berry, C., Thomas, M., Langley, B., Sharma, M., and Kambadur, R. (2002). Single cysteine to tyrosine transition inactivates the growth inhibitory function of Piedmontese myostatin. Am J Physiol Cell Physiol 283, C135–C141.

    Article  CAS  PubMed  Google Scholar 

  • Beyer, T.A., Narimatsu, M., Weiss, A., David, L., and Wrana, J.L. (2013). The TGFβ superfamily in stem cell biology and early mammalian embryonic development. Biochim Biophys Acta Gen Subj 1830, 2268–2279.

    Article  CAS  Google Scholar 

  • Chisada, S., Okamoto, H., Taniguchi, Y., Kimori, Y., Toyoda, A., Sakaki, Y., Takeda, S., and Yoshiura, Y. (2011). Myostatin-deficient medaka exhibit a double-muscling phenotype with hyperplasia and hypertrophy, which occur sequentially during post-hatch development. Dev Biol 359, 82–94.

    Article  CAS  PubMed  Google Scholar 

  • Crispo, M., Mulet, A., Tesson, L., Barrera, N., Cuadro, F., dos Santos-Neto, P., Nguyen, T., Crénéguy, A., Brusselle, L., and Anegón, I. (2015). Efficient generation of myostatin knock-out sheep using CRISPR/Cas9 technology and microinjection into zygotes. PLoS ONE 10, e0136690.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deng, B., Zhang, F., Wen, J., Ye, S., Wang, L., Yang, Y., Gong, P., and Jiang, S. (2017). The function of myostatin in the regulation of fat mass in mammals. Nutr Metab (Lond) 14, 29.

    Article  PubMed  Google Scholar 

  • Gao, Y., Dai, Z., Shi, C., Zhai, G., Jin, X., He, J., Lou, Q., and Yin, Z. (2016). Depletion of myostatin b promotes somatic growth and lipid metabolism in zebrafish. Front Endocrinol 7, 88.

    Article  Google Scholar 

  • Gaylord, T.G., and GatlinIII, D.M. (2000). Dietary lipid level but not l-carnitine affects growth performance of hybrid striped bass (Morone chrysops ♀×M. saxatilis ♂). Aquaculture 190, 237–246.

    Article  CAS  Google Scholar 

  • Gong, D., Tao, M., Xu, L., Hu, F., Wei, Z., Wang, S., Wang, Y., Liu, Q., Wu, C., Luo, K., et al. (2022). An improved hybrid bream derived from a hybrid lineage of Megalobrama amblycephala (♀)×Culter alburnus (♂). Sci China Life Sci 65, 1213–1221.

    Article  CAS  PubMed  Google Scholar 

  • Guo, R., Wan, Y., Xu, D., Cui, L., Deng, M., Zhang, G., Jia, R., Zhou, W., Wang, Z., Deng, K., et al. (2016). Generation and evaluation of myostatin knock-out rabbits and goats using CRISPR/Cas9 system. Sci Rep 6, 29855.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He, J., Zhao, F., Chen, B., Cui, N., Li, Z., Qin, J., Luo, L., Zhao, C., and Li, L. (2023). Alterations in immune cell heterogeneities in the brain of aged zebrafish using single-cell resolution. Sci China Life Sci 66, 1358–1378.

    Article  CAS  PubMed  Google Scholar 

  • Hu, F., Zhong, H., Wu, C., Wang, S., Guo, Z., Tao, M., Zhang, C., Gong, D., Gao, X., Tang, C., et al. (2021). Development of fisheries in China. Reprod Breed 1, 64–79.

    Article  Google Scholar 

  • Johnston, I.A. (2006). Environment and plasticity of myogenesis in teleost fish. J Exp Biol 209, 2249–2264.

    Article  CAS  PubMed  Google Scholar 

  • Kambadur, R., Sharma, M., Smith, T.P.L., and Bass, J.J. (1997). Mutations in myostatin (GDF8) in double-muscled Belgian Blue and piedmontese cattle. Genome Res 7, 910–915.

    Article  CAS  PubMed  Google Scholar 

  • Kerr, T., Roalson, E.H., and Rodgers, B.D. (2005). Phylogenetic analysis of the myostatin gene sub-family and the differential expression of a novel member in zebrafish. Evol Dev 7, 390–400.

    Article  CAS  PubMed  Google Scholar 

  • Khalil, K., Elayat, M., Khalifa, E., Daghash, S., Elaswad, A., Miller, M., Abdelrahman, H., Ye, Z., Odin, R., Drescher, D., et al. (2017). Generation of myostatin gene-edited channel catfish (Ictalurus punctatus) via zygote injection of CRISPR/Cas9 system. Sci Rep 7, 7301.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kishimoto, K., Washio, Y., Yoshiura, Y., Toyoda, A., Ueno, T., Fukuyama, H., Kato, K., and Kinoshita, M. (2018). Production of a breed of red sea bream Pagrus major with an increase of skeletal muscle mass and reduced body length by genome editing with CRISPR/Cas9. Aquaculture 495, 415–427.

    Article  CAS  Google Scholar 

  • Lee, S.J., Huynh, T.V., Lee, Y.S., Sebald, S.M., Wilcox-Adelman, S.A., Iwamori, N., Lepper, C., Matzuk, M.M., and Fan, C.M. (2012). Role of satellite cells versus myofibers in muscle hypertrophy induced by inhibition of the myostatin/activin signaling pathway. Proc Natl Acad Sci USA 109, E2353–E2360.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee, S.J., Lehar, A., Liu, Y., Ly, C.H., Pham, Q.M., Michaud, M., Rydzik, R., Youngstrom, D.W., Shen, M.M., Kaartinen, V., et al. (2020). Functional redundancy of type I and type II receptors in the regulation of skeletal muscle growth by myostatin and activin A. Proc Natl Acad Sci USA 117, 30907–30917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, J., Yang, C., Huang, L., Zeng, K., Cao, X., and Gao, J. (2019). Inefficient ATP synthesis by inhibiting mitochondrial respiration causes lipids to decrease in MSTN-lacking muscles of loach Misgurnus anguillicaudatus. Funct Integr Genomics 19, 889–900.

    Article  CAS  PubMed  Google Scholar 

  • Li, W., Liu, J., Tan, H., Luo, L., Cui, J., Hu, J., Wang, S., Liu, Q., Hu, F., Tang, C., et al. (2018). Asymmetric expression patterns reveal a strong maternal effect and dosage compensation in polyploid hybrid fish. BMC Genomics 19, 517.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li, X.Y., Mei, J., Ge, C.T., Liu, X.L., and Gui, J.F. (2022). Sex determination mechanisms and sex control approaches in aquaculture animals. Sci China Life Sci 65, 1091–1122.

    Article  PubMed  Google Scholar 

  • Liu, Q., Liu, J., Liang, Q., Qi, Y., Tao, M., Zhang, C., Qin, Q., Zhao, R., Chen, B., and Liu, S. (2019a). A hybrid lineage derived from hybridization of Carassius cuvieri and Carassius auratus red var. and a new type of improved fish obtained by backcrossing. Aquaculture 505, 173–182.

    Article  Google Scholar 

  • Liu, Q., Liu, J., Yuan, L., Li, L., Tao, M., Zhang, C., Qin, Q., Chen, B., Ma, M., Tang, C., et al. (2020). The establishment of the fertile fish lineages derived from distant hybridization by overcoming the reproductive barriers. Reproduction 159, R237–R249.

    Article  CAS  PubMed  Google Scholar 

  • Liu, Q., Luo, K., Zhang, X., Liu, F., Qin, Q., Tao, M., Wen, M., Tang, C., and Liu, S. (2021a). A new type of triploid fish derived from the diploid hybrid crucian carp (♀) × autotetraploid fish (♂). Reprod Breed 1, 122–127.

    Article  Google Scholar 

  • Liu, Q., Qi, Y., Liang, Q., Song, J., Liu, J., Li, W., Shu, Y., Tao, M., Zhang, C., Qin, Q., et al. (2019b). Targeted disruption of tyrosinase causes melanin reduction in Carassius auratus cuvieri and its hybrid progeny. Sci China Life Sci 62, 1194–1202.

    Article  CAS  PubMed  Google Scholar 

  • Liu, Q., Qi, Y., Liang, Q., Xu, X., Hu, F., Wang, J., Xiao, J., Wang, S., Li, W., Tao, M., et al. (2018). The chimeric genes in the hybrid lineage of Carassius auratus cuvieri (♀)×Carassius auratus red var. (♂). Sci China Life Sci 61, 1079–1089.

    Article  PubMed  Google Scholar 

  • Liu, Q., Zhang, X., Liu, J., Liu, F., Shi, F., Qin, Q., Tao, M., Tang, C., and Liu, S. (2021b). A new type of allodiploid hybrids derived from female Megalobrama amblycephala × male Gobiocypris rarus. Front Genet 12, 685914.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, S.J. (2010). Distant hybridization leads to different ploidy fishes. Sci China Life Sci 53, 416–425.

    Article  PubMed  Google Scholar 

  • Liu, S., Luo, J., Chai, J., Ren, L., Zhou, Y., Huang, F., Liu, X., Chen, Y., Zhang, C., Tao, M., et al. (2016). Genomic incompatibilities in the diploid and tetraploid offspring of the goldfish × common carp cross. Proc Natl Acad Sci USA 113, 1327–1332.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, S., Wang, S., Liu, Q., Zhou, Y., Zhang, C., Tao, M., and Luo, K. (2022). The summary of fish distant hybridization. In: Liu, S, ed. Fish Distant Hybridization. Singapore: Springer. 325–343.

    Chapter  Google Scholar 

  • McPherron, A.C., and Lee, S.J. (1997). Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci USA 94, 12457–12461.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McPherron, A.C., and Lee, S.J. (2002). Suppression of body fat accumulation in myostatin-deficient mice. J Clin Invest 109, 595–601.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ou, M., Mao, H., Luo, Q., Zhao, J., Liu, H., Zhu, X., Chen, K., and Xu, H. (2019). The DNA methylation level is associated with the superior growth of the hybrid fry in snakehead fish (Channa argus × Channa maculata). Gene 703, 125–133.

    Article  CAS  PubMed  Google Scholar 

  • Ren, L., Li, W., Qin, Q., Dai, H., Han, F., Xiao, J., Gao, X., Cui, J., Wu, C., Yan, X., et al. (2019). The subgenomes show asymmetric expression of alleles in hybrid lineages of Megalobrama amblycephala×Culter alburnus. Genome Res 29, 1805–1815.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ren, L., Zhang, H., Luo, M., Gao, X., Cui, J., Zhang, X., and Liu, S. (2022). Heterosis of growth trait regulated by DNA methylation and miRNA in allotriploid fish. Epigenet Chromatin 15, 19.

    Article  CAS  Google Scholar 

  • Rescan, P.Y. (2005). Muscle growth patterns and regulation during fish ontogeny. Gen Comp Endocrinol 142, 111–116.

    Article  CAS  PubMed  Google Scholar 

  • Rescan, P.Y. (2008). New insights into skeletal muscle development and growth in teleost fishes. J Exp Zool Pt B 310B, 541–548.

    Article  CAS  Google Scholar 

  • Sartori, R., Romanello, V., and Sandri, M. (2021). Mechanisms of muscle atrophy and hypertrophy: implications in health and disease. Nat Commun 12, 330.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schiaffino, S., Dyar, K.A., Ciciliot, S., Blaauw, B., and Sandri, M. (2013). Mechanisms regulating skeletal muscle growth and atrophy. FEBS J 280, 4294–4314.

    Article  CAS  PubMed  Google Scholar 

  • Shan, T., Liang, X., Bi, P., and Kuang, S. (2013). Myostatin knockout drives browning of white adipose tissue through activating the AMPK-PGC1α-Fndc5 pathway in muscle. FASEB J 27, 1981–1989.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi, C., Lou, Q., Fu, B., Jin, J., Huang, J., Lu, Y., Jin, X., He, J., Zhai, G., Xie, S., et al. (2022). Genomic polymorphisms at the crhr2 locus improve feed conversion efficiency through alleviation of hypothalamus-pituitary-interrenal axis activity in gibel carp (Carassius gibelio). Sci China Life Sci 65, 206–214.

    Article  CAS  PubMed  Google Scholar 

  • Tao, B., Tan, J., Chen, L., Xu, Y., Liao, X., Li, Y., Chen, J., Song, Y., and Hu, W. (2021). CRISPR/Cas9 system-based myostatin-targeted disruption promotes somatic growth and adipogenesis in loach, Misgurnus anguillicaudatus. Aquaculture 544, 737097.

    Article  CAS  Google Scholar 

  • Taylor, W.E., Bhasin, S., Artaza, J., Byhower, F., Azam, M., WillardJr., D.H., KullJr., F.C., and Gonzalez-Cadavid, N. (2001). Myostatin inhibits cell proliferation and protein synthesis in C2 C12 muscle cells. Am J Physiol Endocrinol Metab 280, E221–E228.

    Article  CAS  PubMed  Google Scholar 

  • Thomas, M., Langley, B., Berry, C., Sharma, M., Kirk, S., Bass, J., and Kambadur, R. (2000). Myostatin, a negative regulator of muscle growth, functions by inhibiting myoblast proliferation. J Biol Chem 275, 40235–40243.

    Article  CAS  PubMed  Google Scholar 

  • Wang, J., Xiao, J., Zeng, M., Xu, K., Tao, M., Zhang, C., Duan, W., Liu, W.B., Luo, K.K., Liu, Y., et al. (2015a). Genomic variation in the hybrids of white crucian carp and red crucian carp: evidence from ribosomal DNA. Sci China Life Sci 58, 590–601.

    Article  CAS  PubMed  Google Scholar 

  • Wang, K., Ouyang, H., Xie, Z., Yao, C., Guo, N., Li, M., Jiao, H., and Pang, D. (2015b). Efficient generation of myostatin mutations in pigs using the CRISPR/Cas9 system. Sci Rep 5, 16623.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, Y., Liu, Y.J., Tian, L.X., Du, Z.Y., Wang, J.T., Wang, S., and Xiao, W.P. (2005). Effects of dietary carbohydrate level on growth and body composition of juvenile tilapia, Oreochromis niloticus×O. aureus. Aquac Res 36, 1408–1413.

    Article  CAS  Google Scholar 

  • Whittemore, L.A., Song, K., Li, X., Aghajanian, J., Davies, M., Girgenrath, S., Hill, J.J., Jalenak, M., Kelley, P., Knight, A., et al. (2003). Inhibition of myostatin in adult mice increases skeletal muscle mass and strength. Biochem Biophys Res Commun 300, 965–971.

    Article  CAS  PubMed  Google Scholar 

  • Wu, Y., Wu, T., Yang, L., Su, Y., Zhao, C., Li, L., Cai, J., Dai, X., Wang, D., and Zhou, L. (2023). Generation of fast growth Nile tilapia (Oreochromis niloticus) by myostatin gene mutation. Aquaculture 562, 738762.

    Article  CAS  Google Scholar 

  • Xiao, H., Xu, Z., Zhu, X., Wang, J., Zheng, Q., Zhang, Q., Xu, C., Tao, W., and Wang, D. (2022). Cortisol safeguards oogenesis by promoting follicular cell survival. Sci China Life Sci 65, 1563–1577.

    Article  CAS  PubMed  Google Scholar 

  • Xie, S., Niu, D., Wei, K., Dong, Z., and Li, J. (2018). Polymorphisms in the FOXO gene are associated with growth traits in the Sanmen breeding population of the razor clam Sinonovacula constricta. Aquac Fish 3, 177–183.

    Article  Google Scholar 

  • Xu, C., Wu, G., Zohar, Y., and Du, S.J. (2003). Analysis of myostatin gene structure, expression and function in zebrafish. J Exp Biol 206, 4067–4079.

    Article  CAS  PubMed  Google Scholar 

  • Yeh, Y.C., Kinoshita, M., Ng, T.H., Chang, Y.H., Maekawa, S., Chiang, Y.A., Aoki, T., and Wang, H.C. (2017). Using CRISPR/Cas9-mediated gene editing to further explore growth and trade-off effects in myostatin-mutated F4 medaka (Oryzias latipes). Sci Rep 7, 11435.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu, B., Lu, R., Yuan, Y., Zhang, T., Song, S., Qi, Z., Shao, B., Zhu, M., Mi, F., and Cheng, Y. (2016). Efficient TALEN-mediated myostatin gene editing in goats. BMC Dev Biol 16, 26.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yu, P., Wang, Y., Li, Z., Jin, H., Li, L.L., Han, X., Wang, Z.W., Yang, X.L., Li, X.Y., Zhang, X.J., et al. (2022). Causal gene identification and desirable trait recreation in goldfish. Sci China Life Sci 65, 2341–2353.

    Article  CAS  PubMed  Google Scholar 

  • Zhong, Z., Niu, P., Wang, M., Huang, G., Xu, S., Sun, Y., Xu, X., Hou, Y., Sun, X., Yan, Y., et al. (2016). Targeted disruption of sp7 and myostatin with CRISPR-Cas9 results in severe bone defects and more muscular cells in common carp. Sci Rep 6, 22953.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgement

This work was supported by the National Natural Science Foundation of China (32002382, 32293252, U19A2040, 32293254), the National Key Research and Development Program of China (2023YFD2400202), the Natural Science Foundation of Hunan Province (2021JJ40339), the Training Program for Excellent Young Innovators of Changsha (kq2209013), the Earmarked Fund for Agriculture Research System of China (CARS-45), the Laboratory of Lingnan Modern Agriculture Project (NT2021008), the 111 Project (D20007), and Special Science Found of Nansha-South China Agricultural University Fishery Research Institute, Guangzhou.

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Liu, Q., Duan, L., Li, B. et al. The key role of myostatin b in somatic growth in fishes derived from distant hybridization. Sci. China Life Sci. (2024). https://doi.org/10.1007/s11427-023-2487-8

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