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Open Access Highly Accessed Research article

Unresolved orthology and peculiar coding sequence properties of lamprey genes: the KCNA gene family as test case

Huan Qiu13, Falk Hildebrand14, Shigehiro Kuraku12* and Axel Meyer12

Author Affiliations

1 Laboratory for Zoology and Evolutionary Biology, Department of Biology, University of Konstanz, Universitätsstrasse 10, 78457 Konstanz, Germany

2 Konstanz Research School Chemical Biology (KoRS-CB), University of Konstanz, Universitätsstrasse 10, 78457 Konstanz, Germany

3 Bigelow Laboratory for Ocean Sciences, 180 McKown Point Road, West Boothbay Harbor, Maine 04575-0475, USA

4 Bioinformatics and (eco-) systems biology, VIB, Vrije Universiteit Brussel, 1050 Brussels, Belgium

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BMC Genomics 2011, 12:325  doi:10.1186/1471-2164-12-325

Published: 23 June 2011



In understanding the evolutionary process of vertebrates, cyclostomes (hagfishes and lamprey) occupy crucial positions. Resolving molecular phylogenetic relationships of cyclostome genes with gnathostomes (jawed vertebrates) genes is indispensable in deciphering both the species tree and gene trees. However, molecular phylogenetic analyses, especially those including lamprey genes, have produced highly discordant results between gene families. To efficiently scrutinize this problem using partial genome assemblies of early vertebrates, we focused on the potassium voltage-gated channel, shaker-related (KCNA) family, whose members are mostly single-exon.


Seven sea lamprey KCNA genes as well as six elephant shark genes were identified, and their orthologies to bony vertebrate subgroups were assessed. In contrast to robustly supported orthology of the elephant shark genes to gnathostome subgroups, clear orthology of any sea lamprey gene could not be established. Notably, sea lamprey KCNA sequences displayed unique codon usage pattern and amino acid composition, probably associated with exceptionally high GC-content in their coding regions. This lamprey-specific property of coding sequences was also observed generally for genes outside this gene family.


Our results suggest that secondary modifications of sequence properties unique to the lamprey lineage may be one of the factors preventing robust orthology assessments of lamprey genes, which deserves further genome-wide validation. The lamprey lineage-specific alteration of protein-coding sequence properties needs to be taken into consideration in tackling the key questions about early vertebrate evolution.