Kleppe A.S., Bornberg-Bauer E
Translational readthrough goes unseen by natural selection
PLOSGenetics, 2019

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Occasionally during protein synthesis, the ribosome bypasses the stop codon and
continues translation to the next stop codon in frame. This error is called translational
readthrough (TR). Earlier research suggest that TR is a relatively common error, in
several taxa, yet the evolutionary relevance of this translational error is still unclear. By
analysing ribosome profiling data, we have conducted species comparisons between
yeasts to infer conservation of TR between orthologs. Moreover, we infer the
evolutionary rate of error prone and canonically translated proteins to deduct
differential selective pressure. We find that about 40% of error prone proteins in
Schizosaccharomyces pombe do not have any orthologs in Saccharomyces cerevisiae, but
that 60% of error prone proteins in S. pombe are undergoing canonical translation in S.
cerevisiae. Error prone proteins tend to have a higher GC-content in the 3’-UTR, unlike
their canonically translated ortholog. We do not find the same trends for GC-content of
the CDS. We discuss the role of 3’-UTR and GC-content regarding translational
readthrough. Moreover, we find that there is neither selective pressure against or for TR.
We suggest that TR is a near-neutral error that goes unseen by natural selection. We
speculate that TR yield neutral protein isoforms that are not being purged. We suggest
that isoforms, yielded by TR, increase proteomic diversity in the cell, which is readily
available upon sudden environmental shifts and which therefore may become adaptive.