Fig. 1

Architecture of the human POLG transcript. a. Diagram of the primary transcript for POLG. The dashed lines represent exon boundaries (not to scale). The protein product Pol γ contains a mitochondrial targeting sequence at the N-terminus and the rest of the protein consists of several domains that make up the DNA polymerase super-domain. b. UCSC Genome Browser [4] image of (from top to bottom) ATG codons (green) and stop codons (red) in the three theoretical reading frames on the minus strand of chromosome 15; first three exons of previously-annotated POLG transcripts ENST00000268124.10 and ENST00000442287.6; incomplete novel transcript ENST00000650303.1;Synonymous Constraint track showing regions with enhanced synonymous conservation; PhyloCSF tracks for the three minus strand frames; and PhyloCSF Candidate Coding Region (PCCR) track. The cluster of PCCRs suggests coding in some previously unannotated frame. The PhyloCSF signals suggest translation in chromosomal frame 3 in exon 2 and frame 2 in exon 3 (purple rectangles), terminating at a well-conserved stop codon in exon 3. There are no ATG codons in this frame in the 5′ portion of exon 2 or in any frame in exon 1 (dark red rectangles), suggesting that the initiation codon is not ATG. The coding region of ENST00000650303, ORF-Y, begins at a well-conserved CTG codon. The ATG and stop codon of a likely regulatory ORF, ORF-Z are also indicated (black rectangle)