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Background  Fatty acids, a considerable fraction of lipid molecules, participate in fundamental physiological processes. They undergo activation into their corresponding CoA esters for oxidation or esterification into complex lipids (e.g. triglycerides, phospholipids and cholesterol esters), a process that is carried out by acyl-CoA synthases (ACS). Here we analyze the evolution of the gene family encoding for the long-chain acyl-CoA synthetases ( Acsl ) in vertebrates.    Results  By means of phylogenetics and comparative genomics we show that genome duplications (2R) generated the diversity of  Acsl  genes in extant vertebrate lineages. In the vertebrate ancestor two separate genes originated the current  Acsl 1/5/6 and the  Acsl 3/4 gene families, and the extra gene duplicates in teleosts are a consequence of the teleost specific third round of genome duplication (3R). Moreover, the diversity of  Acsl  family members is broader than anticipated. Our strategy uncovered a novel uncharacterized  Acsl- like gene found in teleosts, spotted gar, coelacanth and possibly lamprey, which we designate  Acsl2 . The detailed analysis of the  Acsl2  teleost gene  locus  strongly supports the conclusion that it corresponds to a retained 2R paralogue, lost in tetrapods.    Conclusions  We provide here the first evolutionary analysis of the  Acsl  gene family in vertebrates, showing the specific contribution of 2R/3R to the diversity of this gene family. We find also that the division of ACSL enzymes into two groups predates at least the emergence of deuterostomes. Our study indicates that genome duplications significantly contributed to the elaboration of fatty acid activation metabolism in vertebrates.

Diversity and history of the long-chain acyl-CoA synthetase (Acsl) gene family in vertebrates