Identification of three novel Ca(2+) channel gamma subunit genes reveals molecular diversification by tandem and chromosome duplication.

TitleIdentification of three novel Ca(2+) channel gamma subunit genes reveals molecular diversification by tandem and chromosome duplication.
Publication TypeJournal Article
Year of Publication1999
AuthorsBurgess, DL, Davis, CF, Gefrides, LA, Noebels, JL
JournalGenome Res
Date Published1999 Dec
KeywordsAmino Acid Sequence, Calcium Channels, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 17, Evolution, Molecular, Expressed Sequence Tags, Gene Duplication, Genetic Variation, Humans, Molecular Sequence Data, Multigene Family, Peptides, Phylogeny, Physical Chromosome Mapping, Sequence Alignment

Gene duplication is believed to be an important evolutionary mechanism for generating functional diversity within genomes. The accumulated products of ancient duplication events can be readily observed among the genes encoding voltage-dependent Ca(2+) ion channels. Ten paralogous genes have been identified that encode isoforms of the alpha(1) subunit, four that encode beta subunits, and three that encode alpha(2)delta subunits. Until recently, only a single gene encoding a muscle-specific isoform of the Ca(2+) channel gamma subunit (CACNG1) was known. Expression of a distantly related gene in the brain was subsequently demonstrated upon isolation of the Cacng2 gene, which is mutated in the mouse neurological mutant stargazer (stg). In this study, we sought to identify additional genes that encoded gamma subunits. Because gene duplication often generates paralogs that remain in close syntenic proximity (tandem duplication) or are copied onto related daughter chromosomes (chromosome or whole-genome duplication), we hypothesized that the known positions of CACNG1 and CACNG2 could be used to predict the likely locations of additional gamma subunit genes. Low-stringency genomic sequence analysis of targeted regions led to the identification of three novel Ca(2+) channel gamma subunit genes, CACNG3, CACNG4, and CACNG5, on chromosomes 16 and 17. These results demonstrate the value of genome evolution models for the identification of distantly related members of gene families.

Alternate JournalGenome Res
PubMed ID10613843
PubMed Central IDPMC311002
Grant ListR01 NS029709 / NS / NINDS NIH HHS / United States
NS29709 / NS / NINDS NIH HHS / United States

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