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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 in all
Twinkle sequences outside of Metazoa. Accordingly, we propose that Twinkle likely serves as the primase as well as the helicase
for mtDNA replication in most eukaryotes whose genome encodes it, with the exception of Metazoa.
[Reviewing Editior: Dr. Rüdiger Cerff] 相似文献
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