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Published July 28, 2021 | Submitted + Supplemental Material
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Evolution of a chordate-specific mechanism for myoblast fusion

Abstract

The size of an animal is determined by the size of its musculoskeletal system. Myoblast fusion is an innovative mechanism that allows for multinucleated muscle fibers to compound the size and strength of individual mononucleated cells. However, the evolutionary history of the control mechanism underlying this important process is currently unknown. The phylum Chordata hosts closely related groups that span distinct myoblast fusion states: no fusion in cephalochordates, restricted fusion and multinucleation in tunicates, and extensive, obligatory fusion in vertebrates. To elucidate how these differences may have evolved, we studied the evolutionary origins and function of membrane-coalescing agents Myomaker and Myomixer in various groups of chordates. Here we report that Myomaker likely arose through gene duplication in the last common ancestor of tunicates and vertebrates, while Myomixer appears to have evolved de novo in early vertebrates. Functional tests revealed an unexpectedly complex evolutionary history of myoblast fusion in chordates. A pre-vertebrate phase of muscle multinucleation driven by Myomaker was followed by the later emergence of Myomixer that enables the highly efficient fusion system of vertebrates. Thus, our findings reveal the evolutionary origins of chordate-specific fusogens and illustrate how new genes can shape the emergence of novel morphogenetic traits and mechanisms.

Additional Information

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. This version posted July 25, 2021. We thank trainees G. Gopu, A. Baiju, and E. M. Hicks in Bi laboratory and A. L. Womble from Valdosta State University for technical help. We are grateful to E. N. Olson from University of Texas Southwestern Medical Center for critical reading of the manuscript. We thank H. Li from Ocean University of China, C. CaƱestro from University of Barcelona, S. Kuraku, R. Kusakabe and S. Kuratani from RIKEN, M. Cui from University of Texas Southwestern Medical Center, S. Du from University of Maryland School of Medicine, J. Ziermann from Howard University, Z. Yang from University of College London, Michael Coates and Tetsuto Miyashita from University of Chicago, and F. Razy-Krajka for advice; A. Bigot and V. Mouly from the Myoline platform of the Myology Institute for myoblast cell lines; X. Li from University of Texas Southwestern Medical Center, N. S. Johnson from United States Geological Survey, M. Brindley from University of Georgia for providing materials and reagents. This work was supported by the starting up fund from the University of Georgia to P.B., NIH R00 award HD084814 and NSF award 1940743 to A.S., an NSF Graduate Research Fellowship to C.J.J., Great Lakes Fishery Commission (540810) to S.D.F. and W.L., and NSF award 1354788 to T.A.U. Author contributions: H.Z., R.S., A.S., P.B. designed research; H.Z., R.S., K.K., W.Z., C.J.J., S.L., X.N., L.L., T.A.U., J.Z., L.L., J.P., S.D.F., S.A.G., S.P.S., J.W., J.Z., J.E., D.M., M.E.B., N.V.G., W.L., K.Y., Z.Y., A.S. and P.B. performed research; H.Z., R.S., K.K., W.Z., C.J.J., L.S., X.N., L.L., J.Z., L.L., J.W., W.L., K.Y., Z.Y., A.S. and P.B. analyzed data; A.S. and P.B. wrote the paper. The authors declare that they have no competing interests. Data and materials availability: All data needed to evaluate the conclusions in the paper are present in the paper and/or the Supplementary Materials. Additional data related to this paper may be requested from the authors.

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Submitted - 2021.07.24.453587v1.full.pdf

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Additional details

Created:
August 20, 2023
Modified:
December 13, 2023