Opossum carboxylesterases: sequences, phylogeny and evidence for <it>CES </it>gene duplication events predating the marsupial-eutherian common ancestor

• Main Authors: Chan Jeannie, Holmes Roger S, Cox Laura A, Murphy William J, VandeBerg John L
• Format: Article
• Language: English
• Published: BMC 2008-02-01
• Series: BMC Evolutionary Biology
• Online Access: http://www.biomedcentral.com/1471-2148/8/54

<p>Abstract</p> <p>Background</p> <p>Carboxylesterases (CES) perform diverse metabolic roles in mammalian organisms in the detoxification of a broad range of drugs and xenobiotics and may also serve in specific roles in lipid, cholesterol, pheromone and lung surfactant metabolism. Five CES families have been reported in mammals with human CES1 and CES2 the most extensively studied. Here we describe the genetics, expression and phylogeny of CES isozymes in the opossum and report on the sequences and locations of <it>CES1</it>, <it>CES2 </it>and <it>CES6 </it>'like' genes within two gene clusters on chromosome one. We also discuss the likely sequence of gene duplication events generating multiple <it>CES </it>genes during vertebrate evolution.</p> <p>Results</p> <p>We report a cDNA sequence for an opossum <it>CES </it>and present evidence for <it>CES1 </it>and <it>CES2 </it>like genes expressed in opossum liver and intestine and for distinct gene locations of five opossum <it>CES </it>genes,<it>CES1</it>, <it>CES2.1</it>, <it>CES2.2</it>, <it>CES2.3 </it>and <it>CES6</it>, on chromosome 1. Phylogenetic and sequence alignment studies compared the predicted amino acid sequences for opossum CES with those for human, mouse, chicken, frog, salmon and <it>Drosophila </it>CES gene products. Phylogenetic analyses produced congruent phylogenetic trees depicting a rapid early diversification into at least five distinct CES gene family clusters: <it>CES2, CES1, CES7, CES3</it>, and <it>CES6</it>. Molecular divergence estimates based on a Bayesian relaxed clock approach revealed an origin for the five mammalian CES gene families between 328–378 MYA.</p> <p>Conclusion</p> <p>The deduced amino acid sequence for an opossum cDNA was consistent with its identity as a mammalian <it>CES2 </it>gene product (designated <it>CES2.1</it>). Distinct gene locations for opossum <it>CES1 </it>(1: 446,222,550–446,274,850), three <it>CES2 </it>genes (1: 677,773,395–677,927,030) and a <it>CES6 </it>gene (1: 677,585,520–677,730,419) were observed on chromosome 1. Opossum <it>CES1 </it>and multiple <it>CES2 </it>genes were expressed in liver and intestine. Amino acid sequences for opossum <it>CES1 </it>and three <it>CES2 </it>gene products revealed conserved residues previously reported for human CES1 involved in catalysis, ligand binding, tertiary structure and organelle localization. Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian <it>CES </it>genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods.</p>