TY - JOUR
T1 - Evolutionary pressures on simple sequence repeats in prokaryotic coding regions
AU - Lin, Wei Hsiang
AU - Kussell, Edo
N1 - Funding Information:
Burroughs Wellcome Fund and National Institutes of Health (grant R01-GM-097356 to E.K.). Funding for open access charge: National Institutes of Health (grant R01-GM-097356).
PY - 2012/3
Y1 - 2012/3
N2 - Simple sequence repeats (SSRs) are indel mutational hotspots in genomes. In prokaryotes, SSR loci can cause phase variation, a microbial survival strategy that relies on stochastic, reversible on-off switching of gene activity. By analyzing multiple strains of 42 fully sequenced prokaryotic species, we measure the relative variability and density distribution of SSRs in coding regions. We demonstrate that repeat type strongly influences indel mutation rates, and that the most mutable types are most strongly avoided across genomes. We thoroughly characterize SSR density and variability as a function of N→C position along protein sequences. Using codon-shuffling algorithms that preserve amino acid sequence, we assess evolutionary pressures on SSRs. We find that coding sequences suppress repeats in the middle of proteins, and enrich repeats near termini, yielding U-shaped SSR density curves. We show that for many species this characteristic shape can be attributed to purely biophysical constraints of protein structure. In multiple cases, however, particularly in certain pathogenic bacteria, we observe over enrichment of SSRs near protein N-termini significantly beyond expectation based on structural constraints. This increases the probability that frameshifts result in non-functional proteins, revealing that these species may evolutionarily tune SSR positions in coding regions to facilitate phase variation.
AB - Simple sequence repeats (SSRs) are indel mutational hotspots in genomes. In prokaryotes, SSR loci can cause phase variation, a microbial survival strategy that relies on stochastic, reversible on-off switching of gene activity. By analyzing multiple strains of 42 fully sequenced prokaryotic species, we measure the relative variability and density distribution of SSRs in coding regions. We demonstrate that repeat type strongly influences indel mutation rates, and that the most mutable types are most strongly avoided across genomes. We thoroughly characterize SSR density and variability as a function of N→C position along protein sequences. Using codon-shuffling algorithms that preserve amino acid sequence, we assess evolutionary pressures on SSRs. We find that coding sequences suppress repeats in the middle of proteins, and enrich repeats near termini, yielding U-shaped SSR density curves. We show that for many species this characteristic shape can be attributed to purely biophysical constraints of protein structure. In multiple cases, however, particularly in certain pathogenic bacteria, we observe over enrichment of SSRs near protein N-termini significantly beyond expectation based on structural constraints. This increases the probability that frameshifts result in non-functional proteins, revealing that these species may evolutionarily tune SSR positions in coding regions to facilitate phase variation.
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U2 - 10.1093/nar/gkr1078
DO - 10.1093/nar/gkr1078
M3 - Article
C2 - 22123746
AN - SCOPUS:84859323535
SN - 0305-1048
VL - 40
SP - 2399
EP - 2413
JO - Nucleic acids research
JF - Nucleic acids research
IS - 6
ER -