scholarly journals The RAF oncogenes of vertebrates are ohnologs that derive from the two rounds of whole genome duplications early in vertebrate evolution

2019 ◽  
Author(s):  
Amanda Coward Black ◽  
Mary Clay Bailey ◽  
Marisa Ruane-Foster ◽  
Juan C. Opazo ◽  
Federico G. Hoffmann

ABSTRACTThe Rapidly Accelerated Fibrosarcoma (RAF) kinases are part of large group of serine/threonine-specific protein kinases that play important roles in cell differentiation and organism development. Animal RAF kinases are key connectors in the signaling cascade that links the small G protein RAS and the Mitogen-activated protein kinase phosphorylation pathway. Mutations in the RAF genes have been linked to a number of cancers including melanoma, lung cancer, colorectal cancer, thyroid cancer, and ovarian cancer. Most animals possess a single RAF gene, but vertebrates have three RAF genes in their genomes, named as A-, B-, and C-RAF, the latter also known as RAF-1. The emergence of the multiple copies of vertebrate RAFs is not well resolved, on the one hand, because of sequence and functional similarities, some authors speculate that vertebrate B-Raf is most closely related to the RAF genes of the fruit fly and Caenorhabditis elegans, whereas a competing hypothesis is that the A-, B- and C-RAF paralogs emerged from the two rounds of whole genome duplications that occurred early in the evolution of vertebrates. We applied a comparative approach grounded in synteny and phylogenetic analyses to evaluate these two scenarios. Our results are consistent with the hypothesis that the RAF genes of vertebrates are paralogs generated by whole genome duplications. Thus, the functional similarities between vertebrate B-RAF and invertebrate RAF probably reflect the retention of ancestral characters. Interestingly, data from the literature indicate that B-RAF is the paralog that associated with cancer more strongly, and also yields the most severe phenotypes when knocked out.

Author(s):  
Federico G Hoffmann ◽  
Jay F Storz ◽  
Shigehiro Kuraku ◽  
Michael W Vandewege ◽  
Juan C Opazo

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.


Author(s):  
Amber Harper ◽  
Luis Baudouin Gonzalez ◽  
Anna Schönauer ◽  
Michael Seiter ◽  
Michaela Holzem ◽  
...  

AbstractWhole genome duplications (WGD) have occurred multiple times in the evolution of animals, including in the lineages leading to vertebrates, teleosts, horseshoe crabs and arachnopulmonates. These dramatic genomic events initially produce a wealth of new genetic material, which is generally followed by extensive gene loss. It appears that developmental genes such as homeobox genes, signalling pathway components and microRNAs, however, tend to be more frequently retained in duplicate following WGD (ohnologs). These not only provide the best evidence for the occurrence of WGD, but an opportunity to study its evolutionary implications. Although these genes are relatively well studied in the context of vertebrate WGD, genomic and transcriptomic data for independent comparison in other groups are scarce, with patchy sampling of only two of the five extant arachnopulmonate orders. To improve our knowledge of developmental gene repertoires, and their evolution since the arachnopulmonate WGD, we sequenced embryonic transcriptomes from two additional spider species and two whip spider species and surveyed them for three important gene families: Hox, Wnt and frizzled. We report extensive retention of ohnologs in all four species, further supporting the arachnopulmonate WGD hypothesis. Thanks to improved sampling we were able to identify patterns of likely ohnolog retention and loss within spiders, including apparent differences between major clades. The two amblypygid species have larger ohnolog repertoires of these genes than both spiders and scorpions; including the first reported duplicated Wnt1/wg, the first Wnt10 recovered in an arachnid, and broad retention of frizzled genes. These insights shed light on the evolution of the enigmatic whip spiders, highlight the importance of the comparative approach within lineages, and provide substantial new transcriptomic data for future study.


Author(s):  
Amber Harper ◽  
Luis Baudouin Gonzalez ◽  
Anna Schönauer ◽  
Ralf Janssen ◽  
Michael Seiter ◽  
...  

Abstract Whole genome duplications have occurred multiple times during animal evolution, including in lineages leading to vertebrates, teleosts, horseshoe crabs and arachnopulmonates. These dramatic events initially produce a wealth of new genetic material, generally followed by extensive gene loss. It appears, however, that developmental genes such as homeobox genes, signalling pathway components and microRNAs are frequently retained as duplicates (so called ohnologs) following whole-genome duplication. These not only provide the best evidence for whole-genome duplication, but an opportunity to study its evolutionary consequences. Although these genes are well studied in the context of vertebrate whole-genome duplication, similar comparisons across the extant arachnopulmonate orders are patchy. We sequenced embryonic transcriptomes from two spider species and two amblypygid species and surveyed three important gene families, Hox, Wnt and frizzled, across these and twelve existing transcriptomic and genomic resources for chelicerates. We report extensive retention of putative ohnologs, further supporting the ancestral arachnopulmonate whole-genome duplication. We also found evidence of consistent evolutionary trajectories in Hox and Wnt gene repertoires across three of the six arachnopulmonate orders, with inter-order variation in the retention of specific paralogs. We identified variation between major clades in spiders and are better able to reconstruct the chronology of gene duplications and losses in spiders, amblypygids, and scorpions. These insights shed light on the evolution of the developmental toolkit in arachnopulmonates, highlight the importance of the comparative approach within lineages, and provide substantial new transcriptomic data for future study.


2021 ◽  
Author(s):  
Federico Hoffmann ◽  
Jay Storz ◽  
Shigehiro Kuraku ◽  
Michael Vandewege ◽  
Juan C. Opazo

The globin superfamily of vertebrate genes is a textbook example of how the interplay between local gene duplications, whole-genome duplications, and regulatory changes can facilitate the evolution of novel protein functions. Almost every vertebrate examined possesses copies of hemoglobin and myoglobin in their genomes, and both cytoglobin and neuroglobin are present in the vast majority of vertebrate genomes surveyed as well. The phylogenetic distribution of globin-E, globin-Y and globin-X (GbX), however, is more spotty, suggesting multiple independent gene losses. Globin-X is an enigmatic globin 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, available evidence suggests that GbX may play a role in protecting cells from oxidative damage and in reducing nitrite and it is predicted to be bound to the cell membrane. Recently released genomes from key vertebrate taxa provide an excellent opportunity to address questions about the early stages of evolution of these genes in vertebrates. In the current study, we integrate bioinformatic, 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 the GbX genes of bony vertebrates, and demonstrate that the GbX genes of cyclostomes and gnathostomes have independent duplicative histories. 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 in comparison to other globin genes, and also provide an evolutionary framework for interpreting results of experiments that examine functional properties of GbX and patterns of tissue-specific expression. By identifying GbX genes products of different WGDs in the vertebrate tree of life, 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.


Cell Reports ◽  
2012 ◽  
Vol 2 (5) ◽  
pp. 1387-1398 ◽  
Author(s):  
Param Priya Singh ◽  
Séverine Affeldt ◽  
Ilaria Cascone ◽  
Rasim Selimoglu ◽  
Jacques Camonis ◽  
...  

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 563 ◽  
Author(s):  
Anna Szczepaniak ◽  
Michał Książkiewicz ◽  
Jan Podkowiński ◽  
Katarzyna Czyż ◽  
Marek Figlerowicz ◽  
...  

Acetyl-coenzyme A carboxylase (ACCase, E.C.6.4.1.2) catalyzes acetyl-coenzyme A carboxylation to malonyl coenzyme A. Plants possess two distinct ACCases differing by cellular compartment and function. Plastid ACCase contributes to de novo fatty acid synthesis, whereas cytosolic enzyme to the synthesis of very long chain fatty acids, phytoalexins, flavonoids, and anthocyanins. The narrow leafed lupin (Lupinus angustifolius L.) represents legumes, a plant family which evolved by whole-genome duplications (WGDs). The study aimed on the contribution of these WGDs to the multiplication of ACCase genes and their further evolutionary patterns. The molecular approach involved bacterial artificial chromosome (BAC) library screening, fluorescent in situ hybridization, linkage mapping, and BAC sequencing. In silico analysis encompassed sequence annotation, comparative mapping, selection pressure calculation, phylogenetic inference, and gene expression profiling. Among sequenced legumes, the highest number of ACCase genes was identified in lupin and soybean. The most abundant plastid ACCase subunit genes were accB. ACCase genes in legumes evolved by WGDs, evidenced by shared synteny and Bayesian phylogenetic inference. Transcriptional activity of almost all copies was confirmed. Gene duplicates were conserved by strong purifying selection, however, positive selection occurred in Arachis (accB2) and Lupinus (accC) lineages, putatively predating the WGD event(s). Early duplicated accA and accB genes underwent transcriptional sub-functionalization.


2018 ◽  
Vol 221 (1) ◽  
pp. 565-576 ◽  
Author(s):  
Liming Cai ◽  
Zhenxiang Xi ◽  
André M. Amorim ◽  
M. Sugumaran ◽  
Joshua S. Rest ◽  
...  

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