Diversity and dispersal of a ubiquitous protein family: acyl-CoA dehydrogenases. Nucleic Acids Res

Robert Cedergren Center for Bioinformatics and Genomics, Biochemistry Department, Université de Montréal, 2900 Edouard-Montpetit, Montreal, QC, H3T 1J4, Canada.
Nucleic Acids Research (Impact Factor: 9.11). 08/2009; 37(17):5619-31. DOI: 10.1093/nar/gkp566
Source: PubMed


Acyl-CoA dehydrogenases (ACADs), which are key enzymes in fatty acid and amino acid catabolism, form a large, pan-taxonomic protein family with at least 13 distinct subfamilies. Yet most reported ACAD members have no subfamily assigned, and little is known about the taxonomic distribution and evolution of the subfamilies. In completely sequenced genomes from approximately 210 species (eukaryotes, bacteria and archaea), we detect ACAD subfamilies by rigorous ortholog identification combining sequence similarity search with phylogeny. We then construct taxonomic subfamily-distribution profiles and build phylogenetic trees with orthologous proteins. Subfamily profiles provide unparalleled insight into the organisms' energy sources based on genome sequence alone and further predict enzyme substrate specificity, thus generating explicit working hypotheses for targeted biochemical experimentation. Eukaryotic ACAD subfamilies are traditionally considered as mitochondrial proteins, but we found evidence that in fungi one subfamily is located in peroxisomes and participates in a distinct beta-oxidation pathway. Finally, we discern horizontal transfer, duplication, loss and secondary acquisition of ACAD genes during evolution of this family. Through these unorthodox expansion strategies, the ACAD family is proficient in utilizing a large range of fatty acids and amino acids-strategies that could have shaped the evolutionary history of many other ancient protein families.

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    • "In contrast, mitochondrial ACDH enzymes, which are functional orthologs to peroxisomal ACOX enzymes, can be traced back to an alpha-proteobacterial origin (Shen et al., 2009). "
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    ABSTRACT: Beta-oxidation of fatty acids and detoxification of reactive oxygen species are generally accepted as being fundamental functions of peroxisomes. Additionally, these pathways might have been the driving force favoring the selection of this compartment during eukaryotic evolution. Here we performed phylogenetic analyses of enzymes involved in beta-oxidation of fatty acids in Bacteria, Eukaryota, and Archaea. These imply an alpha-proteobacterial origin for three out of four enzymes. By integrating the enzymes' history into the contrasting models on the origin of eukaryotic cells, we conclude that peroxisomes most likely evolved non-symbiotically and subsequent to the acquisition of mitochondria in an archaeal host cell.
    BioEssays 11/2014; 37(2). DOI:10.1002/bies.201400151 · 4.73 Impact Factor
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    • "One of the a and one of the b subunits group with the fusion gene in Pezizomycotina, which would suggest that this gene could have been the result of a lateral gene transfer between a Pezizomycotina and U. maydis. This would not be the first gene shown to have been transferred from Pezizomycotina to U. maydis (Shen et al., 2009). We checked the location of these genes in the genome of U. maydis and found that they are consecutive but in opposite strands, and therefore cannot be not fused in this species. "
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    ABSTRACT: Gene fusions, yielding the formation of multidomain proteins, are evolutionary events that can be utilized as phylogenetic markers. Here we describe a fusion gene comprising the α and β subunits of succinyl-coA synthetase, an enzyme of the TCA cycle, in Pezizomycotina fungi. This fusion is present in all Pezizomycotina with complete genome sequences and absent from all other organisms. Phylogenetic analysis of the α and β subunits of succinyl-CoA synthetase suggests that both subunits were duplicated and retained in Pezizomycotina while one copy was lost from other fungi. One of the duplicated copies was then fused in Pezizomycotina. Our results suggest that the fusion of the α and β subunits of succinyl-CoA synthetase can be used as a molecular marker for membership in the Pezizomycotina subphylum. If a species has the fusion it can be reliably classified as Pezizomycotina, while the absence of the fusion is suggestive that the species is not a member of this subphylum.
    Genetics and Molecular Biology 10/2011; 34(4):669-75. DOI:10.1590/S1415-47572011005000040 · 1.20 Impact Factor
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    • "The ACSs identified corresponded to ACS bubblegum family members 1 and 2 (ACSBG1–ACSBG2) and ACS family member 3 (ACSF3), which activates fatty acids to form acyl-CoA, thus allowing their transport and metabolism [19]. The ACD protein family catalyzes the oxidation of diverse acyl-CoA compounds produced during the degradation of fat and protein to enoyl-CoA [20]. ACD subfamilies are distinguished by the metabolic pathways in which they participate and by their substrate specificity. "
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    ABSTRACT: The origin of eukaryotes remains a fundamental question in evolutionary biology. Although it is clear that eukaryotic genomes are a chimeric combination of genes of eubacterial and archaebacterial ancestry, the specific ancestry of most eubacterial genes is still unknown. The growing availability of microbial genomes offers the possibility of analyzing the ancestry of eukaryotic genomes and testing previous hypotheses on their origins. Here, we have applied a phylogenomic analysis to investigate a possible contribution of the Myxococcales to the first eukaryotes. We conducted a conservative pipeline with homologous sequence searches against a genomic sampling of 40 eukaryotic and 357 prokaryotic genomes. The phylogenetic reconstruction showed that several eukaryotic proteins traced to Myxococcales. Most of these proteins were associated with mitochondrial lipid intermediate pathways, particularly enzymes generating reducing equivalents with pivotal roles in fatty acid β-oxidation metabolism. Our data suggest that myxococcal species with the ability to oxidize fatty acids transferred several genes to eubacteria that eventually gave rise to the mitochondrial ancestor. Later, the eukaryotic nucleocytoplasmic lineage acquired those metabolic genes through endosymbiotic gene transfer. Our results support a prokaryotic origin, different from α-proteobacteria, for several mitochondrial genes. Our data reinforce a fluid prokaryotic chromosome model in which the mitochondrion appears to be an important entry point for myxococcal genes to enter eukaryotes.
    PLoS ONE 07/2011; 6(7):e21989. DOI:10.1371/journal.pone.0021989 · 3.23 Impact Factor
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