Dating is often only approximate and there are no fossils of the majority of early or Fossils of most organisms are so rare that it is not possible to trace their horse, which seems to have many fossilised ancestors, has produced hot debate. In contrast, the haemoglobin of lamprey (a jawless fish-like parasite) differs from. Main · Videos; Aamna sharif dating We riffed thru 30 the first service. fish dating sites without registering hemoglobins from bacteria too many fish dating site. More recently, multiple additional family members have been The functions and expression sites of these different globin genes in .. the ray-finned fish Cygb clade is too weak to resolve the evolution of this globin .. Hemoglobins from bacteria to man: evolution of different patterns of gene expression.
Hemoglobins are also used for oxygen transport in invertebrates Riggs ; Dixon et al. Many non-vertebrates have gigantic extracellular hemoglobins, in some species formed by as many as monodomain subunits in a multimeric protein, and in others by covalent linkage into very long polypeptide chains reviewed in Terwilliger The invertebrate hemoglobins are homologous to the vertebrate hemoglobins, and they form a distinct branch in a phylogenetic tree of hemoglobins Fig.
Org Evol Glb Genes
Hemoglobins are present in plants, both the leghemoglobins with specialized functions in root nodules Brisson and Verma ; Appleby as well as the broadly distributed, nonsymbiotic hemoglobins Andersson et al. Interestingly, the genes for plant and invertebrate hemoglobins have a similar structure. Both groups of genes have three introns separating four exons, with at least two introns in identical positions Fig. The similarities in gene structure and the amino acid sequences of the encoded proteins strongly support the hypothesis of a common ancestor to both groups of hemoglobins, showing that the evolutionary history of hemoglobin genes predates the divergence of plants and animals, roughly 1.
It is likely the middle intron was lost prior to the divergence of the vertebrate globin genes, all of which have only two introns.
Phylogeny of Echinoderm Hemoglobins
The structures of illustrative contemporary hemoglobin genes are shown on the right, with exons denoted by dark boxes and introns by white boxes. The position in the hemoglobin a-helical structure of the amino acid encoded at the site of interruption is indicated over the intron, and the loss of the central intron in the ancestor to vertebrates is marked by a vertical arrow. The evolutionary pathway is indicated by the other arrows.
This "tree" is a gene tree, and grouping of of a yeast hemoglobin gene with bacterial hemoglobin genes may reflect a horizontal gene transfer. Estimated times of divergence in millions of years Myr are given at selected nodes. Given that the hemoglobins in the major groups of multicellular organisms - plants, invertebrates and vertebrate animals - are used for storage and transport of oxygen, one might have expected hemoglobins to be absent from unicellular organisms.
It was thought that simple diffusion was sufficient to provide adequate oxygen inside the cells of unicellular, freepsilon-living organisms. The latter two hemoglobins are actually two-domain proteins, one binding heme and the other binding flavin cofactors, which usually plays a role in redox reactions.
Also, the hemoglobin from Vitreoscilla can serve as a terminal electron acceptor during respiration in vivo Dikshit et al. Recent studies clearly show that the hemoglobins in unicellular organisms have enzymatic functions and are not oxygen-transporting proteins. Each of these flavohemoglobins is a nitric oxide dioxygenase, catalyzing the conversion of nitric oxide to nitrate. Other functions have also been proposed for bacterial hemoglobins. For instance, the hemoglobin from Vitreoscilla can serve as a terminal electron acceptor during respiration in vivo Dikshit et al.
Hemoglobins involved in catalytic conversions of nitric oxide and oxygen are not limited to microorganisms. A hemoglobin found in the perienteric fluid of the parasitic worm Ascaris lumbricoides also catalyzes reactions between oxygen and nitric oxide, producing nitrate Minning et al.
However, the chemical mechanism is different from that of the microbial flavohemoglobins, and Mining et al. In mammals, hemoglobins not only transport oxygen, but they also help regulate nitric oxide levels. This binding is favored in oxyhemoglobin, and retains the bioactivity of nitric oxide. Nitric oxide can subsequently be released from deoxyhemoglobin Jia et al. Since nitric oxide is a major regulator of blood pressure, these new findings indicate that hemoglobin is involved in the control of blood pressure in ways that may facilitate efficient delivery of oxygen to tissues.
Furthermore, the interplay between binding of oxygen and nitric oxide to hemoglobin and effects on vasodilation and constriction may have therapeutic applications e. The variety of functions now found for hemoglobins raises the issue of whether the microbial proteins are truly homologous to the hemoglobins from plants and animals. The amino acid sequence comparisons certainly support a common ancestor to all these sequences, as illustrated in the summary phylogenetic tree Fig. Despite the low percent identity e.
The threepsilon-dimensional structures strongly support the conclusion that all these hemoglobins share a common ancestor. Indeed, hemoglobins may be part of a larger family of hemoproteins. Although this is not a heme binding protein per se, it does bind a linear tetrapyrrole pigment derived from heme.
The structural comparisons indicate that genes for at least some other hemoproteins share a common ancestor with hemoglobin genes Fig. These observations all indicate that the gene encoding hemoglobin is truly ancient, i. This divergence has been dated at approximately 3. Hence the primordial function of hemoglobin may have had little to do with molecular oxygen Hardison, The enzymatic functions of hemoglobins found in contemporary microorganisms and nematodes, involving nitric oxide metabolism, provide some insight into the early functions of hemoglobins Durner et al.
Because the separation between archaebacteria and eukaryotes appears to have occurred after the divergence of eubacteria from eukaryotes both of which have hemoglobinsone may anticipate finding homologs to hemoglobins in archae as well. An automated analysis of genome sequences has included an archaebacterial gene from Methanococcus jannaschii in an orthologous group Tatusov et al. Further investigation of this and other archaebacterial genes related to hemoglobins, revealed from the whole genome sequencing, should provide even more insights into the origin and range of functions of hemoglobins.
An issue that has received much attention is the age of the introns, and whether they serve to separate genes into exons that encode distinct protein domains Gilbert The three introns of globin genes in plants and invertebrates, dating back approximately 1. This has lent support to the model that introns are old, and are the remnants of a process that combined exons to generate genes with new structures and functions Gilbert However, the hemoglobin genes from protists have introns in positions unique to many of the species, and those of eubacteria have no introns Fig.
Attempts to explain this degree of heterogeneity as the result of differential loss of introns require a very large number of introns to be proposed in the ancestral gene.Things Men HATE about Female POF Profiles!!!
An alternative explanation is that at least some of the introns in the protist hemoglobin genes arose by insertion of new introns in each lineage, consistent with the "introns late" model Stoltzfus et al. Thus it seems unlikely that all the introns in contemporary hemoglobin genes were present in the ancestral gene i. However, this does not rule out the possibility that some introns, perhaps those still in hemoglobin genes in multicellular organisms, were in the ancestral gene.
Evolution of alpha- and beta-globin gene clusters in vertebrates Human hemoglobins are encoded at two separate loci, the beta-like globin gene cluster on chromosome 11p As shown in Fig. Evolutionary pathways for alpha- and beta-globin gene cluters in vertebrates. Each gene is indicated simply by a Greek letter.
Contemporary gene clusters are on the right Hardison and references thereinand the deduced course of evolution to them is shown by a series of arrows.
The effective transport of oxygen between tissues by hemoglobin is accomplished by highly cooperative binding of oxygen when its concentration is high e. In vertebrates, this cooperativity is accomplished by the interactions between the alpha- and beta-globin subunits of hemoglobin see chapter 8 by M.
Vertebrate hemoglobins are kept at high concentrations inside erythrocytes, specialized cells devoted to the task of oxygen transport. Thus the divergence of the ancestral globin gene into the alpha-globin and beta-globin genes Fig. These goals have been accomplished by different mechanisms in other evolutionary lineages. For instance, the basis for cooperativity in non-vertebrate hemoglobins is quite different, in many cases involving reversible dissociation of hemoglobin subunits upon oxygenation Riggs Vertebrate alpha- and beta-globin genes likely arose by the duplication and subsequent divergence of an ancestral globin gene in early vertebrates.
This would have generated a linked set of alpha- and beta-globin genes Fig. Gene duplication and divergence continued independently in each of these lineages to generate the contemporary gene clusters. This is illustrated by the avian and mammalian beta-globin gene clusters, which contain multiple genes expressed differentially in development Fig.
In both species the epsilon- globin gene is expressed in embryos and the beta-globin gene is expressed in adults. However, the sequence of each chicken beta-like globin gene is equally similar to each human gene Goodman et al. This indicates that the gene duplications generating these beta-globin gene clusters occurred after the species diverged.
Much is now known about the organization of alpha- and beta-globin gene clusters in contemporary mammals, which can be understood in terms of descent from common gene clusters in an ancestral eutherian mammal.
Analysis of DNA sequences showed that a given globin gene in one species is usually more related to a gene in another mammal than to other globin genes in the same species Hardison ; Goodman et al. This indicated that these genes are orthologous, i. The exceptions to this observation could be explained by gene duplications within a single mammalian lineage, e. Finding orthologs to epsilon- gamma- eta- delta- and beta-globin genes, in that order, in virtually all eutherian mammals suggested that the ancestral eutherian had at least this set of genes Fig.
This hypothesis was strongly supported by the observation of substantial regions of sequence similarity outside the coding regions of the genes, in the introns and flanking regions Hardies et al. As will be discussed more extensively below, some but not all of these matching sequences are strong candidates for regulatory function.
The long regions of matching sequences outside functional regions, and thus not subject to any obvious selection, were key observations in establishing this model for evolution of the mammalian globin gene clusters. Deletions, conversions and duplications of both single genes and blocks of genes have occurred in each mammalian order to generate the current gene clusters reviewed in Collins and Weissman ; Hardison Pathways to contemporary mammalian beta-globin gene clusters.
Genes are indicated by boxes, and orthologous genes have the same type of fill. The presumptive presence of an LCR in marsupials is indicated by the grey outline R. References are in the text and in reviews Collins and Weissman ; Hardison Estimates based on rates of divergence indicated that the epsilon- gamma- and eta-globin genes arose from duplications of one ancestral gene, whereas the delta- and beta-globin genes arose by duplication of a different gene, perhaps prior to the divergence of eutherian and metatherian marsupials and monotreme mammals Goodman et al.
Evolution and Expression of Tissue Globins in Ray-Finned Fishes
This prediction was verified by genomic analysis of marsupials Koop and Goodman ; Cooper et al. Thus the model shown in Fig. One important ramification of this model is that orthologous genes have not retained the same time of expression during development in all mammalian orders.
The gamma-globin gene in most mammals is expressed in embryonic erythroid cells, but in simian primates, including humans, it is expressed predominantly in fetal erythroid cells. Concomitantly with the fetal recruitment of the gamma-globin gene, expression of the beta-globin gene has been delayed in higher primates so that in humans it is expressed primarily in post-natal life.
In other mammals, the beta-globin gene is expressed in both fetal and adult erythroid cells. The delta-globin gene is expressed at low levels in adult humans, but is silent in some mammals, and is expressed at high levels in others.
In contrast, the epsilon-globin gene in each mammalian species is expressed only in embryonic erythroid cells derived from the yolk sac. Within the beta-globin gene clusters of mammals, conservation of stage-specific expression is seen only for this gene, which is located closest to the distal locus control region LCR, see below and chapter 6 by B. Perhaps the embryonic restriction of epsilon-globin gene expression is related to this spatial relationship, with active expression in the embryonic lineage due to its proximity to the LCR, followed by silencing in the fetal and adult definitive lineage of erythroid cells see chapter 14 by G.
Both the proximity to the LCR and the embryonic restriction to expression is conserved in all mammalian epsilon-globin genes examined. The beta-globin gene clusters of humans and mice are embedded within a large cluster of olfactory receptor genes, or ORGs Bulger et al. This arrangement suggests that the beta-globin genes transposed into a prepsilon-existing array of ORGs.
Enhancer sequences from this ORG are brought in proximity to the gamma-globin genes by the HPFH-1 deletion, and this may play a role in the increased expression of gamma-globin genes in adults carrying this deletion Feingold and Forget, Pathways to contemporary mammalian alpha-globin gene clusters.
The presumptive presence of a homolog to HS the distal major control region in mammals besides human and mouse is indicated by the grey outline. References are in the text and in reviews Collins and Weissman ; Hardison ; Hardison and Miller Orthologous relationships have been assigned primarily on the basis of DNA sequence matches outside the genes Hardison and Gelinas ; Sawada and Schmid ; Wernke and Lingrel ; Flint et al.
Since a variant of the arrangement 5'-zeta-zeta-alpha-alpha-theta-3' is found in all contemporary mammals examined, it is likely that these genes were present in this order in the gene cluster of the ancestral eutherian mammal.
The timing of expression is well-conserved among these mammals. The zeta-globin genes are expressed only in embryonic erythroid cells, whereas the alpha-globin genes are expressed in all erythroid cells, albeit at lower levels at the embryonic stage Rohrbaugh and Hardison ; Leder et al. The theta-globin genes are still not well understood. The human theta-globin gene is transcribed at low levels but does not encode any known polypeptide found in human hemoglobins Hsu et al.
It is a feature of every mammalian alpha-like globin gene cluster examined Fig. The retention of the theta-globin genes is suggestive of some functional importance, but perhaps not for encoding a globin polypeptide. Although no examples of recruitment for expression at different developmental stages are seen in the alpha-like globin gene clusters, some genes have lost their function during evolution.
In particular, based on upstream sequence matches, the human ya1-globin pseudogene appears to be orthologous to an active alpha-globin gene in goats and horse Fig. The inactivation of ya1-gene is accompanied by the loss of a CpG island that encompasses its homologs Bird et al.
The orthologous relationships in Fig. The more recent duplication in primates has left a long region of sequence similarity surrounding the alpha-globin genes Hess et al. Not all mammals have retained a pair of active alpha-globin genes. Rabbits are the exception, with only one alpha-globin gene Cheng et al. Curiously, this gene cluster has expanded by block duplications of a zeta-zeta-theta gene triad Cheng et al. All the vertebrate globin gene clusters examined to date encode subunits of hemoglobins differentially expressed in embryonic and adult erythroid cells Fig.
Likewise, hemoglobin synthesis is developmentally regulated in some invertebrates Terwilliger and different plant leghemoglobins are made at progressive stages of nodulation Hyldigamma-Nielsen et al. Thus the ability to express different hemoglobins at particular developmental stages, i. It is likely that they were differentially expressed during development in these ancestral species. Given that all contemporary vertebrates have developmentally regulated hemoglobin genes encoding proteins used for oxygen transport in erythrocytes, it would have been reasonable to expect that the molecular mechanisms of globin gene regulation would be conserved in vertebrates.
Certainly, the coordinated and balanced expression of alpha- and beta-globin genes to produce the heterotypic tetramer alpha2beta2 in erythrocytes should be a particularly easy aspect of regulation to explain. However, much has changed between the alpha-like and beta-like globin gene clusters since their duplication.
Tissue-specific gene expression is frequently correlated with an increased accessibility of the chromatin only in expressing cells, and hence "opening" of a chromatin domain is a key step in activation of many tissue-specific genes.
This is the case for beta-like globin genes of mammals Groudine et al. Thus the mammalian alpha-globin genes have several characteristics associated with constitutively expressed, "housekeeping" genes. Additionally, the alpha-globin genes are replicated early in S phase in all cells a time when most expressed genes are replicatedwhereas beta-globin genes are replicated early in S phase only in cells expressing them Calza et al. In keeping with the presence of CpG islands, the alpha-globin gene cluster is not methylated in any cell types Bird et al.
Thus the strikingly different genomic contexts of the two gene clusters affect several aspects of DNA and chromatin metabolism, including timing of replication, extent of methylation, and the type of chromatin into which the loci are packaged. Rather than selecting for similarities to insure coordinate and balanced expression, the processes of evolution at these two loci have made them quite different.
Differences in chromatin structure between alpha- and beta-globin gene clusters of humans. Globin genes and distal control regions are shown as filled boxes. HS is located within an intron white box of the gene exons of this gene are shown as black boxeslocated upstream of the zeta-globin gene and transcribed in the opposite orientation. Developmentally stable DNase hypersensitive sites HSs are shown as filled arrows, and those that occur at specific developmental stages when the associated gene is expressed are shown as white triangles.
CpG islands are shown as boxes with horizontal lines. None are in the beta-globin gene. References are in the text. Both have distal control elements, called the locus control region or LCR for beta-globin genes reviewed in Grosveld et al.
However, they differ in the range of functions associated with them. The beta-globin LCR is required for tissue-specific chromosomal domain opening Forrester et al. This includes the two ray-finned fish superorders Osteoglossomorpha and Elopomorpha, which, early in teleost evolution, split from the ancestor to the superorder Clupeocephala including lineages where globin diversity has been well-characterized, e.
Finally, a systematic overview of expression of nonblood globins is yet to be achieved across the major teleost lineages in comparison to a ray-finned fish that did not undergo tsWGD, e. This latter work may be useful to contextualize globin roles that have evolved specifically within teleosts, including with respect to tsWGD. We employed phylogenetic, comparative genomic, and quantitative expression analyses to define and characterize full gene repertoires from a range of lineages, many previously unstudied.
Our findings provide new insights into the remarkable functional-evolutionary diversity of globin genes in different fish lineages. Materials and Methods Bioinformatics Globin gene family protein-coding sequences from a number of vertebrate species were obtained from NCBI http: Full details of databases and accession numbers are provided in supplementary table S1Supplementary Material online.
- Associated Data
Seventeen globin gene family member sequences used in the study that were acquired from unpublished transcriptome databases for osteoglossiform species more details in supplementary table S1Supplementary Material online are provided within the supplementary material supplementary dataset S1Supplementary Material online. Comparative analyses of synteny for genomic neighborhoods proximal to GbX genes was determined manually by inspection of assemblies from Nile tilapia Oreochromis niloticus, northern pike Esox lucius, Atlantic salmon Salmo salar, and spotted gar L.
The final alignment, consisting of sequences and aligned sites supplementary dataset S2Supplementary Material onlinewas uploaded to Mega v. Further phylogenetic analyses were performed on GbX, Mb, and Cygb nucleotide protein-coding sequences, with the goal to provide better resolution to poorly resolved branching patterns i.