Natural selection retains overrepresented out-of-frame stop codons against frameshift peptides in prokaryotes
BMC Genomics. 2010 Sep 9;11(1):491. [Epub ahead of print]
Natural selection retains overrepresented out-of-frame
stop codons against frameshift peptides in
Tse H, Cai JJ, Tsoi HW, Lam EP, Yuen KY.
BACKGROUND: Out-of-frame stop codons (OSCs) occur naturally in
coding sequences of all organisms, providing a mechanism of early
termination of translation in incorrect reading frame so that the
metabolic cost associated with frameshift events can be reduced.
Given such a functional significance, we expect statistically
overrepresented OSCs in coding sequences as a result of a
widespread selection. Accordingly, we examined available
prokaryotic genomes to look for evidence of this selection.
RESULTS: The complete genome sequences of 990 prokaryotes were
obtained from NCBI GenBank. We found that low G+C content coding
sequences contain significantly more OSCs and G+C content at
specific codon positions were the principal determinants of OSC
usage bias in the different reading frames. To investigate if there
is overrepresentation of OSCs, we modeled the trinucleotide and
hexanucleotide biases of the coding sequences using Markov models,
and calculated the expected OSC frequencies for each organism using
a Monte Carlo approach. More than 93% of 342 phylogenetically
representative prokaryotic genomes contain excess OSCs.
Interestingly the degree of OSC overrepresentation correlates
positively with G+C content, which may represent a compensatory
mechanism for the negative correlation of OSC frequency with G+C
content. We extended the analysis using additional compositional
bias models and showed that lower-order bias like codon usage and
dipeptide bias could not explain the OSC overrepresentation. The
degree of OSC overrepresentation was found to correlate negatively
with the optimal growth temperature of the organism after
correcting for the G+C% and AT skew of the coding sequence.
CONCLUSIONS: The present study uses approaches with statistical
rigor to show that OSC overrepresentation is a widespread
phenomenon among prokaryotes. Our results support the hypothesis
that OSCs carry functional significance and have been selected in
the course of genome evolution to act against unintended frameshift
occurrences. Some results also hint that OSC overrepresentation
being a compensatory mechanism to make up for the decrease in OSCs
in high G+C organisms, thus revealing the interplay between two
different determinants of OSC frequency.
PMID: 20828396 [PubMed - as supplied by publisher] Free
Back to Publications