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Evolutionary analysis of the carnitine- and choline acyltransferases suggests distinct evolution of CPT2 versus CPT1 and related variants
Authors:Marjanne D van der Hoek  Ole Madsen  Jaap Keijer  Feike R van der Leij
Institution:1. Applied Research Centre Food and Dairy, Van Hall Larenstein University of Applied Sciences, P.O. box 1528, 8901BV Leeuwarden, The Netherlands;2. Human and Animal Physiology, Wageningen University, P.O. box 338, 6700AH Wageningen, The Netherlands;3. Animal Breeding and Genomics Centre, Wageningen University, P.O. box 338, 6700AH Wageningen, The Netherlands
Abstract:Carnitine/choline acyltransferases play diverse roles in energy metabolism and neuronal signalling. Our knowledge of their evolutionary relationships, important for functional understanding, is incomplete. Therefore, we aimed to determine the evolutionary relationships of these eukaryotic transferases. We performed extensive phylogenetic and intron position analyses. We found that mammalian intramitochondrial CPT2 is most closely related to cytosolic yeast carnitine transferases (Sc-YAT1 and 2), whereas the other members of the family are related to intraorganellar yeast Sc-CAT2. Therefore, the cytosolically active CPT1 more closely resembles intramitochondrial ancestors than CPT2. The choline acetyltransferase is closely related to carnitine acetyltransferase and shows lower evolutionary rates than long chain acyltransferases. In the CPT1 family several duplications occurred during animal radiation, leading to the isoforms CPT1A, CPT1B and CPT1C. In addition, we found five CPT1-like genes in Caenorhabditis elegans that strongly group to the CPT1 family. The long branch leading to mammalian brain isoform CPT1C suggests that either strong positive or relaxed evolution has taken place on this node. The presented evolutionary delineation of carnitine/choline acyltransferases adds to current knowledge on their functions and provides tangible leads for further experimental research.
Keywords:AMPK  AMP-activated protein kinase  cChAT  common form of choline acetyltransferase  ChAT  choline acetyltransferase  CPT  carnitine palmitoyltransferase  CrAT  carnitine acetyltransferase  CrOT  carnitine octanoyltransferase  HSCoA  free coenzyme A  pChAT  peripheral form of choline acetyltransferase  TM  transmembrane  Evolutionary history  Mitochondria  Acetyltransferase  Palmitoyltransferase  Ghrelin
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