Evolution and expression of tissue globins in ray-finned fishes

Abstract

The globin gene family encodes oxygen-binding hemeproteins conserved across the major branches of multicellular life. The origins and evolutionary histories of complete globin repertoires have been established for many vertebrates, but there remain major knowledge gaps for ray-finned fish. Therefore, we used phylogenetic, comparative genomic and gene expression analyses to discover and characterize canonical “non-blood” globin family members (i.e., myoglobin, cytoglobin, neuroglobin, globin-X, and globin-Y) across multiple ray-finned fish lineages, revealing novel gene duplicates (paralogs) conserved from whole genome duplication (WGD) and small-scale duplication events. Our key findings were that: (1) globin-X paralogs in teleosts have been retained from the teleost-specific WGD, (2) functional paralogs of cytoglobin, neuroglobin, and globin-X, but not myoglobin, have been conserved from the salmonid-specific WGD, (3) triplicate lineage-specific myoglobin paralogs are conserved in arowanas (Osteoglossiformes), which arose by tandem duplication and diverged under positive selection, (4) globin-Y is retained in multiple early branching fish lineages that diverged before teleosts, and (5) marked variation in tissue-specific expression of globin gene repertoires exists across ray-finned fish evolution, including several previously uncharacterized sites of expression. In this respect, our data provide an interesting link between myoglobin expression and the evolution of air breathing in teleosts. Together, our findings demonstrate great-unrecognized diversity in the repertoire and expression of nonblood globins that has arisen during ray-finned fish evolution.

Genetic and functional diversity of the multiple lungfish myoglobins

“…As none of the other globins (with the exception of GbE; see ) or, to the best of our knowledge, any other gene family show signs of gene amplification, it is unlikely that the multiplication of the Mb genes is caused by hypothetic whole‐genome amplifications putatively linked to the large lungfish genomes. Duplicated and even triplicated Mb genes have been known from some teleost species . Lungfish are the current record holders with up to nine distinct Mbs .…”

Lessons from the post-genomic era: Globin diversity beyond oxygen binding and transport

“…Globin Y (GbY) was reported in reptiles, platypus, ray-finned fishes, coelacanth, spotted gar, elephant shark and amphibians [ 69 , 308 ] ( Fig. 2 ).…”

“…Genomic analyses showed that GbY localizes at the 3’ end of the α-globin gene cluster [ 309 ]. Moreover, the sites of expression vary among species: gill and spleen in spotted gar; intestine, gill and spleen in elephant shark; a low expression in several tissues including kidney, lung, brain or blood in western painted turtle [ 79 , 308 ]. Up to date, due to the lack of experimental evidence for the physiological role of GbY, its function remains obscure.…”

“…During evolution, Globin X (GbX) emerged in early Metazoans from a common ancestor around 800 million years ago and shows 25–30% sequence identity to Ngb [ 76 , 79 , 308 ]. In vertebrates its expression is restricted to certain taxa, including lampreys, fish, amphibians and some reptiles, whereas no detectable expression was reported in birds and mammals [ 69 , 82 , 310 ] ( Fig.…”

“…2 ). However, the sites and levels of expression may be variable depending on the species and include brain, eye, intestine, liver, spleen, and heart [ 79 , 308 ]. In zebrafish, GbX is mainly expressed in the eye and the central nervous system, and its levels are oxygen-dependently regulated, with a significant decrease under hypoxic conditions [ 311 , 312 ].…”