Globin E is a myoglobin-related, respiratory protein highly expressed in lungfish oocytes

Abstract

Globins are a classical model system for the studies of protein evolution and function. Recent studies have shown that – besides the well-known haemoglobin and myoglobin – additional globin-types occur in vertebrates that serve different functions. Globin E (GbE) was originally identified as an eye-specific protein of birds that is distantly related to myoglobin. GbE is also present in turtles and the coelacanth but appeared to have been lost in other vertebrates. Here, we show that GbE additionally occurs in lungfish, the closest living relatives of the tetrapods. Each lungfish species harbours multiple (≥5) GbE gene copies. Surprisingly, GbE is exclusively and highly expressed in oocytes, with mRNA levels that exceed that of myoglobin in the heart. Thus, GbE is the first known oocyte-specific globin in vertebrates. No GbE transcripts were found in the ovary or egg transcriptomes of other vertebrates, suggesting a lungfish-specific function. Spectroscopic analysis and kinetic studies of recombinant GbE1 of the South American lungfish Lepidosiren paradoxa revealed a typical pentacoordinate globin with myoglobin-like O2-binding kinetics, indicating similar functions. Our findings suggest that the multiple copies of GbE evolved to enhance O2-supply in the developing embryo of lungfish, analogous to the embryonic and fetal haemoglobins of other vertebrates. In evolution, GbE must have changed its expression site from oocytes to eyes, or vice versa.

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 .…”

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“…Cytoglobin is an intracellular respiratory globin ubiquitously expressed almost in all tissues. 66 It has been shown to prevent oxidative stress through scavenging excess ROS, 67 thereby maintaining physiological ROS levels. 68 Cytoglobin protected the cardiac progenitor cells against oxidative stress and promoted their survival.…”

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

“…Neuroglobin (Ngb) emerged in early Metazoans around 800 million years ago from a common ancestor to Adgb and Globin X [ 69 , 77 ] and is found in vertebrates including ray-finned fishes, coelacanths, amphibians, lizards, turtles, birds, monotremes, marsupials and mammals, with the exception of lampreys, cartilaginous fishes and lungfishes [ 69 , 202 ] ( Fig. 2 ).…”

“…More recently, a study showed that lungfish bear also multiple copies of GbE . Surprisingly, in contrast to avian location, the major sites of expression were ovaries and oocytes, whereas no detectable mRNA was found in the eye [ 202 ]. The physiological role of GbE in lungfish and more particularly in oocytes is still unclear, but it is conceivable that its main function might be to retrieve oxygen from water and support embryonic development.…”