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Phylogeny of the Vitamin K 2,3-Epoxide Reductase (VKOR) Family and Evolutionary Relationship to the Disulfide Bond Formation Protein B (DsbB) Family
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Nutrients 2015, 7(8), 6250-6280;

VKORC1 and VKORC1L1: Why do Vertebrates Have Two Vitamin K 2,3-Epoxide Reductases?

Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn 53105, Germany
Im Hermeshain 6, Frankfurt am Main 60388, Germany
Author to whom correspondence should be addressed.
Received: 18 May 2015 / Revised: 8 July 2015 / Accepted: 15 July 2015 / Published: 30 July 2015
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Among all cellular life on earth, with the exception of yeasts, fungi, and some prokaryotes, VKOR family homologs are ubiquitously encoded in nuclear genomes, suggesting ancient and important biological roles for these enzymes. Despite single gene and whole genome duplications on the largest evolutionary timescales, and the fact that most gene duplications eventually result in loss of one copy, it is surprising that all jawed vertebrates (gnathostomes) have retained two paralogous VKOR genes. Both VKOR paralogs function as entry points for nutritionally acquired and recycled K vitamers in the vitamin K cycle. Here we present phylogenetic evidence that the human paralogs likely arose earlier than gnathostomes, possibly in the ancestor of crown chordates. We ask why gnathostomes have maintained these paralogs throughout evolution and present a current summary of what we know. In particular, we look to published studies about tissue- and developmental stage-specific expression, enzymatic function, phylogeny, biological roles and associated pathways that together suggest subfunctionalization as a major influence in evolutionary fixation of both paralogs. Additionally, we investigate on what evolutionary timescale the paralogs arose and under what circumstances in order to gain insight into the biological raison d’être for both VKOR paralogs in gnathostomes. View Full-Text
Keywords: evolution; subfunctionalization; paralog; vitamin K; VKOR; VKORC1; VKORC1L1 evolution; subfunctionalization; paralog; vitamin K; VKOR; VKORC1; VKORC1L1

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Oldenburg, J.; Watzka, M.; Bevans, C.G. VKORC1 and VKORC1L1: Why do Vertebrates Have Two Vitamin K 2,3-Epoxide Reductases? Nutrients 2015, 7, 6250-6280.

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