Abstract
BackgroundDuring evolutionary history, molecular mechanisms have emerged to cope with deleterious mutations. Frameshift insertions in protein-coding sequences are extremely rare because they disrupt the reading frame. There are a few known examples of their correction through translational frameshifting, a process that enables ribosomes to skip nucleotides during translation to regain proper reading frame. Corrective frameshifting has been proposed to act on the single base pair insertion at position 174 of the mitochondrial NADH dehydrogenase subunit 3 gene (ND3) that has been observed in several turtles and birds. However, the relatively sparse taxonomic representation has hampered our understanding of the evolution of this insertion in vertebrates.ResultsHere, we analyzed 87,707 ND3 sequences from 10,309 vertebrate taxa to reveal the evolutionary history of this insertion and its common genomic characteristics. We confirmed that the insertion only appears in turtles and birds and reconstructed that it evolved independently in both groups with complex patterns of gains and losses. The insertion was observed in almost all bird orders but was absent in all members of the diverse Passeriformes. We found strong conservation in the nucleotides surrounding the insertion in both turtles and birds, which implies that the insertion enforces structural constraints that could be involved in its correction.ConclusionsOur study demonstrates that frameshifts can be widespread and can be retained for millions of years if they are embedded in a conserved sequence theme.
Highlights
During evolutionary history, molecular mechanisms have emerged to cope with deleterious mutations
Corrective frameshifting has been proposed to act on the single base pair insertion at position 174 of the mitochondrial NADH dehydrogenase subunit 3 gene (ND3) that has been observed in several turtles and birds
We found strong conservation in the nucleotides surrounding the insertion in both turtles and birds, which implies that the insertion enforces structural constraints that could be involved in its correction
Summary
Comparative analysis of molecular sequences across the diversity of life lets us discover which molecular mechanisms have been conserved and which have been modified throughout evolution. The “out-of-frame” model proposes that the recruited tRNA skips the additional nucleotide in the A-site [11] This out-of-frame correction of the frameshift is thought to act in glass sponges because of the conserved genomic features in several mitochondrial genes containing frameshifts [13]. The out-of-frame model may apply to the frameshift insertion found in the mitochondrial genomes of certain turtles and birds, where a +1 frameshift insertion occurs at position 174 of the NADH dehydrogenase 3 gene (hereafter ND3–174+1) [9]. We further investigated sequence conservation and codon usage patterns around the insertion site to identify potential common sequence motifs associated with the absence or presence of the frameshift insertion. In the +1 corrected reading frame leaving out A-175, the codon following the insertion (position 176–178) was a GTA codon (encoding valine, a nonpolar amino acid) in all sequences (Fig. 2D). We could not perform this check for the frameshift insertions in the other 4 turtle species because no additional genomic or transcriptomic data was available
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