The Evolution of The Cardiac Myosinome of Gnathostomes

Abstract

The term myosinome has been recently coined to define the set and distribution of myosins in a particular tissue. Since different myosin isoforms have different contractile properties, the myosinome of cardiac fibers determines their type of contraction. Classically, it has been assumed that the cardiac myosinome of vertebrates is mainly formed by only two myosin heavy chain (MYH) isoforms, which are heterogeneously distributed in the heart: whereas MYH6 is more abundant in the inflow, MYH7 predominates in the outflow myocardium. However, this concept has been recently questioned after the identification of significant amounts of additional isomyosins in hearts of other vertebrates, i.e. MYH15 in the amphibian outflow myocardium; MYH2 and MYH7B in the inflow and outflow myocardia of chondrichthyans, respectively. To study the diversity and evolution of the cardiac myosinome in vertebrates, we have analyzed the inflow and outflow myocardia of representative specimens of polypteriforms, lepisosteiforms, acipenseriforms and dipnoi, by means of a specific myosin extraction method followed by quantitative proteomic analysis. We have identified five additional MYH isoforms (MYH1, MYH3, MYH4, MYH8 and Fast-skeletal MYH), each abundantly expressed in the inflow or outflow myocardia of distinct vertebrate groups, demonstrating that the cardiac myosinome in vertebrates is more diverse than initially thought. In general, the diversity of MYH isoforms has increased in most osteichthyes and decreased in teleosts and tetrapods. Therefore, not all vertebrates share the MYH6/MYH7 pattern observed in teleosts, birds and mammals, which can be considered a specialized vertebrate myosinome. In addition, the abundance and distribution of these MYH isoforms in the morpho-functionally diverse hearts studied allow raising several hypotheses on the evolution of the vertebrate cardiac myosinome: While MYH4 seems to be an autapomorphy of non-tetrapod sarcopterygians, MYH7B can be considered an ancient myosin, only present in hearts with a primitive anatomical design. The primitive type of cardiac contraction in gnathostomes with a linear heart anatomy and a long conus arteriosus might require the expression of MYH7B together with MYH1 and Fast-skeletal MYH. Cardiac MYH2 expression may have appeared in association with the development of a specialized cardiac conduction system, whereas that of MYH3 and MYH8 might be associated with adaptation to environments with low oxygen tension. Further studies are needed to confirm these hypotheses on the evolution of the cardiac myosinome, which constitutes a new research field on cardiovascular evolution.