Evolution of Vertebrate Ryanodine Receptors Family in Relation to Functional Divergence and Conservation

Abstract

SummaryRyanodine receptors (RyRs), the large homotetrameric protein complexes, regulate the release of calcium from intracellular stores into the cytosol and play vital roles in the excitation-contraction coupling of cells. However, the evolutionary relationship of RyRs in vertebrates has yet to be elucidated. We identified 22 RyRs from Homo sapiens, Mus musculus, Rattus norvegicus, Gallus gallus, Anolis carolinensis, Rana catesbeiana, and Danio rerio. The phylogenetic relationship, motifs analysis and reconstruction of ancestral RyRs showed that the members of RyR family in vertebrates were grouped into three clades: the RyR1 clade, the RyR2 clade, and the RyR3 clade. Positive selection existed in RyR gene evolution, which is consistent in three site models, and gene ontology (GO) analysis showed that the evolution of RyR family in vertebrates promotes RyRs function differentiation. At last, we predicted 140 mutation sites which may be involved in diseases and 57 phosphorylation sites among RyR1 sequence in human, as well as 61 mutation sites and 70 phosphorylation sites in human RyR2 sequences. Most of these potential sites are arranged in clusters. Our work provides insight into the origin and evolutionary process of RyRs in vertebrates, facilitating their functional investigations in the future.(Int Heart J 2017; 58: 969-977)

Ca2+ as a coordinator of skeletal muscle differentiation, fusion and contraction

“…The emergence of fast-and slowtwitching muscle fibres in the vertebrates appears to align with differences in the mechanism of myoblast fusion and the sequence divergence in MYMK and MYMX paralogs. A similar appearance and subsequent divergence of genes within chordates were previously reported for the molecular evolution of other myopathy-associated CRGs such as the RyRs and ferlin family members, suggesting that MYMK, MYMX and the CRGs coevolved in the chordate lineage [121][122][123]. In addition, Kirrel and the receptor-ligand pair Jam-b/Jam-c, which are essential for myoblast fusion in zebrafish [5,83,115,124], do not exhibit an apparent muscle phenotype in knockout mice [125][126][127].…”

Excitation–Contraction Coupling in the Goldfish (Carassius auratus) Intact Heart

“…In the last 10 years, fish hearts have become a very popular model for studying heart function ( Nemtsas et al, 2010 ; Huttner et al, 2013 ; Ravens, 2018 ; van Opbergen et al, 2018b ; Zhang et al, 2018 ). In developmental studies ( Novak et al, 2006 ; Chi et al, 2010 ; Chablais and Jazwinska, 2012 ; Ramachandran et al, 2013 ; Ding et al, 2017 ), the zebrafish ( Danio rerio ) has been the model of choice not only for the possibility of performing transgenesis ( Chopra et al, 2010 ; Huttner et al, 2013 ; Konantz and Antos, 2014 ; Serbanovic-Canic et al, 2017 ), but also for studying cardiac physiology of larger mammals, including humans ( Nemtsas et al, 2010 ; Ravens, 2018 ; van Opbergen et al, 2018b ). Despite the numerous advantages of using the zebrafish model as an experimental approach to study cardiac function, there are some disadvantages of this model as well.…”