Twinkle, the mitochondrial replicative DNA helicase, is widespread in the eukaryotic radiation and may also be the mitochondrial DNA primase in most eukaryotes.

Journal of Molecular Evolution
Timothy E Shutt, Michael W Gray

Abstract

Recently, the human protein responsible for replicative mtDNA helicase activity was identified and designated Twinkle. Twinkle has been implicated in autosomal dominant progressive external ophthalmoplegia (adPEO), a mitochondrial disorder characterized by mtDNA deletions. The Twinkle protein appears to have evolved from an ancestor shared with the bifunctional primase-helicase found in the T-odd bacteriophages. However, the question has been raised as to whether human Twinkle possesses primase activity, due to amino acid sequence divergence and absence of a zinc-finger motif thought to play an integral role in DNA binding. To date, a primase protein participating in mtDNA replication has not been identified in any eukaryote. Here we investigate the wider phylogenetic distribution of Twinkle by surveying and analyzing data from ongoing EST and genome sequencing projects. We identify Twinkle homologues in representatives from five of six major eukaryotic assemblages ("supergroups") and present the sequence of the complete Twinkle gene from two members of Amoebozoa, a supergroup of amoeboid protists at the base of the opisthokont (fungal/metazoan) radiation. Notably, we identify conserved primase motifs including the zinc finger ...Continue Reading

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