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Molecular evolution of Drosophila Cdc6, an essential DNA replication-licensing gene, suggests an adaptive choice of replication origins.

Wiggins, Benjamin and Malik, Harmit (2007) Molecular evolution of Drosophila Cdc6, an essential DNA replication-licensing gene, suggests an adaptive choice of replication origins. Fly, 1 (3). pp. 155-163. ISSN 1933-6942

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Increased size of eukaryotic genomes necessitated the use of multiple origins of DNA replication, and presumably selected for their efficient spacing to ensure rapid DNA replication. The sequence of these origins remains undetermined in metazoan genomes, leaving important questions about the selective constraints acting on replication origins unanswered. We have chosen to study the evolution of proteins that recognize and define these origins every cell cycle, as a surrogate to the direct analysis of replication origins. Among these DNA replication proteins is the essential Cdc6 protein, which acts to license origins for replication. We find that two different species pairs of Drosophila show evidence of positive selection in Cdc6 in their highly conserved C-terminal AAA-ATPase domain. We also identified amino acid segments that are highly conserved in the N-terminal tail of Cdc6 proteins from various Drosophila species, but are not conserved even in closely related insect species. Instead, we find that the N-terminal tails of Cdc6 proteins vary extensively in size and sequence across different eukaryotic lineages. Our results suggest that choice of origin firing may be significantly altered in closely related species, as each set of replication proteins optimizes to its own genomic landscape.

Item Type: Article
Additional Information: This article is available to subscribers only via the URL above for the first twelve months post-publication. May - June 2007 Issue
PubMed ID: 18618020
PMCID: PMC2447932
Grant Numbers: R01 GM074108-03
Keywords or MeSH Headings: Animals; Cell Cycle Proteins/chemistry/*genetics; Conserved Sequence; DNA Replication/genetics; Drosophila/classification/*genetics/metabolism; Drosophila Proteins/chemistry/*genetics; Drosophila melanogaster/genetics; Evolution, Molecular; *Genes, Insect; Molecular Sequence Data; Phylogeny; Replication Origin; Selection (Genetics); Species Specificity
Subjects: Cellular and Organismal Processes > Evolution
Cellular and Organismal Processes > Genetic processes > DNA replication
Molecules > Proteins
Depositing User: Library Staff
Date Deposited: 30 Jul 2008 19:41
Last Modified: 14 May 2010 21:31

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