Acyl-CoA Dehydrogenases: Dynamic History of Protein Family Evolution

Abstract

The acyl-CoA dehydrogenases (ACADs) are enzymes that catalyze the α,β-dehydrogenation of acyl-CoA esters in fatty acid and amino acid catabolism. Eleven ACADs are now recognized in the sequenced human genome, and several homologs have been reported from bacteria, fungi, plants, and nematodes. We performed a systematic comparative genomic study, integrating homology searches with methods of phylogenetic reconstruction, to investigate the evolutionary history of this family. Sequence analyses indicate origin of the family in the common ancestor of Archaea, Bacteria, and Eukaryota, illustrating its essential role in the metabolism of early life. At least three ACADs were already present at that time: ancestral glutaryl-CoA dehydrogenase (GCD), isovaleryl-CoA dehydrogenase (IVD), and ACAD10/11. Two gene duplications were unique to the eukaryotic domain: one resulted in the VLCAD and ACAD9 paralogs and another in the ACAD10 and ACAD11 paralogs. The overall patchy distribution of specific ACADs across the tree of life is the result of dynamic evolution that includes numerous rounds of gene duplication and secondary losses, interdomain lateral gene transfer events, alteration of cellular localization, and evolution of novel proteins by domain acquisition. Our finding that eukaryotic ACAD species are more closely related to bacterial ACADs is consistent with endosymbiotic origin of ACADs in eukaryotes and further supported by the localization of all nine previously studied ACADs in mitochondria.

Transposon Mutagenesis of Salmonella enterica Serovar Enteritidis Identifies Genes That Contribute to Invasiveness in Human and Chicken Cells and Survival in Egg Albumen

“…Similar to S. Gallinarum, S. Enteritidis SPI-14 contains six open reading frames (ORFs) (SEN0800 to SEN0805). We identified one SPI-14 mutant with an insertion in SEN0803, which encodes a putative acyl-coenzyme A (Co-A) dehydrogenase that participates in alpha and beta dehydrogenation of acyl-CoA esters in both fatty acid and amino acid metabolism (92). In S. Typhimurium, a fatty acyl-CoA dehydrogenase is important for survival under conditions of carbon starvation (86), whereas in the plant pathogen Burkholderia cenocepacia, this enzyme is required for rough-colony morphology, biofilm production, and virulence (89).…”

Burkholderia cenocepacia ShvR-Regulated Genes That Influence Colony Morphology, Biofilm Formation, and Virulence

“…Acyl-CoA dehydrogenases are enzymes that participate in alpha and beta dehydrogenation of acyl-CoA esters in both fatty acid and amino acid metabolism (53). Examination of the closely related B. cenocepacia J2315 genome sequence revealed that there are several paralogs of acyl-CoA dehydrogenases, and these enzymes may act on structurally different fatty acids or fatty acids of different lengths (27,30).…”

Evolution of peroxisomes illustrates symbiogenesis

“…However, the surprising (universal?) presence of the ACAD-11 protein of unknown function in peroxisomes [19][20][21] might indicate a different scenario. The protein is of alpha-bacterial origin and most likely came along with the pre-mitochondrial bacterium.…”