Whole-Genome Duplications and the Diversification of the Globin-X Genes of Vertebrates

Abstract

Globin-X (GbX) is an enigmatic member of the vertebrate globin gene family with a wide phyletic distribution that spans protostomes and deuterostomes. Unlike canonical globins such as hemoglobins and myoglobins, functional data suggest that GbX does not have a primary respiratory function. Instead, evidence suggests that the monomeric, membrane-bound GbX may play a role in cellular signaling or protection against the oxidation of membrane lipids. Recently released genomes from key vertebrates provide an excellent opportunity to address questions about the early stages of the evolution of GbX in vertebrates. We integrate bioinformatics, synteny, and phylogenetic analyses to characterize the diversity of GbX genes in non-teleost ray-finned fishes, resolve relationships between the GbX genes of cartilaginous fish and bony vertebrates, and demonstrate that the GbX genes of cyclostomes and gnathostomes derive from independent duplications. Our study highlights the role that whole-genome duplications (WGDs) have played in expanding the repertoire of genes in vertebrate genomes. Our results indicate that GbX paralogs have a remarkably high rate of retention following WGDs relative to other globin genes, and provide an evolutionary framework for interpreting results of experiments that examine functional properties of GbX and patterns of tissue-specific expression. By identifying GbX paralogs that are products of different WGDs, our results can guide the design of experimental work to explore whether gene duplicates that originate via WGDs have evolved novel functional properties or expression profiles relative to singleton or tandemly duplicated copies of GbX.

A Revised Perspective on the Evolution of Troponin I and Troponin T Gene Families in Vertebrates

“…This is not surprising because cyclostome genomes are unusual with respect to nucleotide, codon, and amino acid composition ( Qiu et al 2011 ; Kuraku 2013 ) that complicate the resolution of orthology based on phylogenies. In some cases, synteny is informative to resolve ambiguous gene phylogenies ( Kuraku and Meyer 2012 ; Hoffmann et al 2010 ; Campanini et al 2015 ), but in others such as the TNNI - TNNT pairs, synteny shows similarities with gnathostomes but ultimately is not informative, as in the globin X genes of vertebrates ( Hoffmann et al 2021 ). Nevertheless, the presence of multiple TNNI - TNNT pairs in both groups is consistent with the possibility that the last common ancestor of vertebrates possessed four TNNI - TNNT pairs in its genome.…”

“…Mammalian TNNI genes are located in close proximity to TNNT paralogs in human and mouse genomes: TNNI2 with TNNT3 , TNNI3 with TNNT1 , and TNNI1 with TNNT2 ( Chong and Jin 2009 ) and there is also some limited evidence for this in fish ( Genge et al 2016 ). This is intriguing because whole-genome duplications (WGDs) have played a key role in expanding the gene repertoire of early vertebrates ( Hoffmann et al 2021 , 2012 ; Zavala et al 2017 ), and because the teleost whole-genome duplication has been linked to the functional diversification of the zebrafish TNNI paralogs ( Genge et al 2016 ). As such, the diversity in TNNI and TNNT families appears to have arisen through a tandem duplication followed by successive rounds of whole-genome duplication ( Chong and Jin 2009 ; Rasmussen and Jin 2021 ).…”

A revised perspective on the evolution of troponin I and troponin T in vertebrates

“…This is not surprising because cyclostome genomes are unusual with respect to nucleotide, codon and amino acid composition (Qiu et al 2011; Kuraku 2013) that complicate the resolution of orthology based on phylogenies. In some cases, synteny is informative to resolve ambiguous gene phylogenies (Kuraku & Meyer 2012; Hoffmann et al 2010; Campanini et al 2015), but in others such as the TNNI - TNNT pairs, synteny shows similarities with gnathostomes but ultimately is not informative, as in the globin X genes of vertebrates (Hoffmann et al 2021). Nevertheless, the presence of multiple TNNI - TNNT pairs in both groups provides a strong indication that the last common ancestor of vertebrates possessed four TNNI - TNNT pairs in its genome.…”

“…Mammalian TNNI genes are located in close proximity to TNNT paralogs in human and mouse genomes: TNNI2 with TNNT3, TNNI3 with TNNT1, and TNNI1 with TNNT2 (Chong & Jin 2009) and there is also some limited evidence for this in fish (Genge et al 2016). This is intriguing because whole-genome duplications (WGDs) have played a key role in expanding the gene repertoires of early vertebrates (Hoffmann et al 2021(Hoffmann et al , 2012Zavala et al 2017), and because the teleost wholegenome duplication has been linked to the functional diversification of the zebrafish TNNI paralogs (Genge et al 2016). As such, the diversity in TNNI and TNNT families appears to have arisen through a tandem duplication followed by successive rounds of whole-genome duplication (Chong & Jin 2009;Rasmussen & Jin 2021).…”

Evolutionary Insight into Immunothrombosis as a Healing Mechanism

“…These marine animals emerged at the onset of the Cambrian period [ 2 , 8 ] ( Figure 1 ) roughly 540 million years ago (Mya). However, the Cambrian radiation, which might have been preceded by the first whole-genome duplication event [ 10 , 11 ], also witnessed the emergence of other physiological innovations, including a true endothelium, a closed and increasingly pressurized circulatory system, blood cell-type diversification, and the adaptive immune system ( Figure 1 ) [ 11 , 12 , 13 , 14 ].…”