Whole-Genome Duplication and the Functional Diversification of Teleost Fish Hemoglobins

Abstract

Subsequent to the two rounds of whole-genome duplication that occurred in the common ancestor of vertebrates, a third genome duplication occurred in the stem lineage of teleost fishes. This teleost-specific genome duplication (TGD) is thought to have provided genetic raw materials for the physiological, morphological, and behavioral diversification of this highly speciose group. The extreme physiological versatility of teleost fish is manifest in their diversity of blood–gas transport traits, which reflects the myriad solutions that have evolved to maintain tissue O2 delivery in the face of changing metabolic demands and environmental O2 availability during different ontogenetic stages. During the course of development, regulatory changes in blood–O2 transport are mediated by the expression of multiple, functionally distinct hemoglobin (Hb) isoforms that meet the particular O2-transport challenges encountered by the developing embryo or fetus (in viviparous or oviparous species) and in free-swimming larvae and adults. The main objective of the present study was to assess the relative contributions of whole-genome duplication, large-scale segmental duplication, and small-scale gene duplication in producing the extraordinary functional diversity of teleost Hbs. To accomplish this, we integrated phylogenetic reconstructions with analyses of conserved synteny to characterize the genomic organization and evolutionary history of the globin gene clusters of teleosts. These results were then integrated with available experimental data on functional properties and developmental patterns of stage-specific gene expression. Our results indicate that multiple α- and β-globin genes were present in the common ancestor of gars (order Lepisoteiformes) and teleosts. The comparative genomic analysis revealed that teleosts possess a dual set of TGD-derived globin gene clusters, each of which has undergone lineage-specific changes in gene content via repeated duplication and deletion events. Phylogenetic reconstructions revealed that paralogous genes convergently evolved similar functional properties in different teleost lineages. Consistent with other recent studies of globin gene family evolution in vertebrates, our results revealed evidence for repeated evolutionary transitions in the developmental regulation of Hb synthesis.

Gene duplication, genome duplication, and the functional diversification of vertebrate globins

“…The ancestral linkage arrangement of the proto α- and β-globin genes is still retained in the genomes of some modern-day amphibians and teleost fish (e.g., Gillemans et al 2003; Jeffreys et al 1980; Wetten et al 2010; Opazo et al 2012). In amniote vertebrates, by contrast, the α- and β-like globin genes are located on different chromosomes, reflecting the fact that the ancestral β-globin gene was transposed to a new chromosomal location in the amniote common ancestor (Hardison 2008; Patel et al 2008, 2010).…”

“…7). In fact, comparative genomic analyses of conserved synteny (Hoffmann et al 2011; Opazo et al 2012) demonstrated that both of the Cygb -defined paralogons descend from chromosome ‘e’ in the reconstructed proto-karyotype of the teleost ancestor (Nakatani et al 2005). The additional round of WGD in teleost fishes also spurred the diversification of the α- and β-globin gene clusters (Opazo et al 2012), but available data suggest that the Ngb , GbX , Cygb , and Mb genes reverted to the single-copy state in all or most teleost lineages.…”

“…Multiple rounds of duplication and divergence have produced diverse repertoires of α- and β-like globin genes that are ontogenetically regulated such that functionally distinct Hb isoforms are expressed during different stages of prenatal development and postnatal life (Alev et al 2009; Brittain 2002; Hardison 2001; Hoffmann et al 2008a,b; Opazo et al 2008a,b, 2009; Storz et al 2011b). Surprisingly, however, phylogenetic analyses of the α- and β-globin gene families have revealed that genes with similar stage-specific expression patterns in different species do not necessarily represent 1:1 orthologs that were inherited from a common ancestor (Czelusniak et al 1982; Hoffmann et al 2010b; Opazo et al 2008a; Storz et al 2011a; Opazo et al 2012). In many cases, the genes represent the products of independent, lineage-specific duplication events, and their similar expression patterns and functional properties are attributable to convergent evolution.…”

CpG island evolution in the mammalian DHRS4 gene cluster and its role in the regulation of gene transcription

“…For example, duplications or mutations in globulin reflect the metabolic demands and environmental oxygen availability during the different embryonic or post-birth life stages of an individual, or during the infection of erythrocytes by the malarial parasite (Lam and Jeffreys, 2006;Opazo et al, 2013); duplications in the AQP7 gene, which codes for a family of water-selective membrane channels, is representative of the adaptations in thermoregulation and energy utilization through biological transmembrane transport (Dumas et al, 2007). Previous research has also suggested that mutations and duplications in the genes could also lead to the development of proteins that are harmful to the species; therefore, there is a high possibility that approximately 90% of the new copied genes is pseudogenized at the epigenetic level, affecting its functionality (Rodin and Riggs, 2003;Katju and Bergthorsson, 2013).…”

Depletion of suppressor of cytokine signaling-1a causes hepatic steatosis and insulin resistance in zebrafish

“…Additional genome duplication also occurs in the stem lineage of teleost fishes to yield duplicate members of SOCS genes in the zebrafish genome corresponding to some of the mammal SOCS members (34). Zebrafish socs1a has been found to exhibit significant expression in the liver (20).…”