Nucleic Acids Research Advance Access originally published online on July 22, 2009
Nucleic Acids Research 2009 37(17):5619-5631; doi:10.1093/nar/gkp566
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Nucleic Acids Research, 2009, Vol. 37, No. 17 5619-5631
© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Computational Biology |
Diversity and dispersal of a ubiquitous protein family: acyl-CoA dehydrogenases
Robert Cedergren Center for Bioinformatics and Genomics, Biochemistry Department, Université de Montréal, 2900 Edouard-Montpetit, Montreal, QC, H3T 1J4, Canada
*To whom correspondence should be addressed. Tel: +1 514 343 6111 2848; Fax: +1 514 343 2210; Email: yaoqing.shen{at}umontreal.ca
Received May 18, 2009. Revised June 17, 2009. Accepted June 18, 2009.
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 β-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.