Evolution of a chordate-specific mechanism for myoblast fusion

Haifeng Zhang, Renjie Shang, Kwantae Kim, Wei Zheng, Christopher J. Johnson, Lei Sun, Xiang Niu, Liang Liu, Jingqi Zhou, Lingshu Liu, Zheng Zhang, Theodore A. Uyeno, Jimin Pei, Skye D. Fissette, Stephen A. Green, Sukhada P. Samudra, Junfei Wen, Jianli Zhang, Jonathan T. Eggenschwiler, Douglas B. MenkeMarianne E. Bronner, Nick V. Grishin, Weiming Li, Kaixiong Ye, Yang Zhang, Alberto Stolfi, Pengpeng Bi

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Vertebrate myoblast fusion allows for multinucleated muscle fibers to compound the size and strength of mononucleated cells, but the evolution of this important process is unknown. We investigated 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 a complex evolutionary history of myoblast fusion. A prevertebrate phase of muscle multinucleation driven by Myomaker was followed by the later emergence of Myomixer that enables the highly efficient fusion system of vertebrates. Evolutionary comparisons between vertebrate and nonvertebrate Myomaker revealed key structural and mechanistic insights into myoblast fusion. Thus, our findings suggest an evolutionary model of chordate fusogens and illustrate how new genes shape the emergence of novel morphogenetic traits and mechanisms.

Original languageEnglish (US)
Article numbereadd2696
JournalScience Advances
Issue number35
StatePublished - Sep 2022

ASJC Scopus subject areas

  • General


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