@article {129162, title = {Shifts in mutation spectra enhance access to beneficial mutations.}, journal = {Proc Natl Acad Sci U S A.}, volume = {120}, year = {2023}, month = {05/2023}, pages = {e2207355120}, abstract = {

Biased mutation spectra are pervasive, with wide variation in the magnitude of mutational biases that influence genome evolution and adaptation. How do such diverse biases evolve? Our experiments show that changing the mutation spectrum allows populations to sample previously undersampled mutational space, including beneficial mutations. The resulting shift in the distribution of fitness effects is advantageous: Beneficial mutation supply and beneficial pleiotropy both increase, while deleterious load reduces. More broadly, simulations indicate that reducing or reversing the direction of a long-term bias is always selectively favored. Such changes in mutation bias can occur easily via altered function of DNA repair genes. A phylogenetic analysis shows that these genes are repeatedly gained and lost in bacterial lineages, leading to frequent bias shifts in opposite directions. Thus, shifts in mutation spectra may evolve under selection and can directly alter the outcome of adaptive evolution by facilitating access to beneficial mutations.

}, doi = {10.1073/pnas.2207355120}, author = {Sane, Mrudula and Diwan, Gaurav D and Bhat, BA and Wahl, LM and Agashe, Deepa} } @article {35144, title = {Wobbling forth and drifting back: The evolutionary history and impact of bacterial tRNA modifications.}, journal = {Mol Biol Evol}, year = {2018}, month = {2018 May 28}, abstract = {

Along with tRNAs, enzymes that modify anticodon bases are a key aspect of translation across the tree of life. tRNA modifications extend wobble pairing, allowing specific ("target") tRNAs to recognize multiple codons and cover for other ("non-target") tRNAs, often improving translation efficiency and accuracy. However, the detailed evolutionary history and impact of tRNA modifying enzymes has not been analyzed. Using ancestral reconstruction of five tRNA modifications across 1093 bacteria, we show that most modifications were ancestral to eubacteria, but were repeatedly lost in many lineages. Most modification losses coincided with evolutionary shifts in non-target tRNAs, often driven by increased bias in genomic GC and associated codon use, or by genome reduction. In turn, the loss of tRNA modifications stabilized otherwise highly dynamic tRNA gene repertoires. Our work thus traces the complex history of bacterial tRNA modifications, providing the first clear evidence for their role in the evolution of bacterial translation.

}, issn = {1537-1719}, doi = {10.1093/molbev/msy110}, author = {Diwan, Gaurav D and Agashe, Deepa} } @article {4892, title = {The Frequency of Internal Shine-Dalgarno-like Motifs in Prokaryotes.}, journal = {Genome Biol Evol}, volume = {8}, year = {2016}, month = {2016}, pages = {1722-33}, abstract = {

In prokaryotes, translation initiation typically depends on complementary binding between a G-rich Shine-Dalgarno (SD) motif in the 5{\textquoteright} untranslated region of mRNAs, and the 3{\textquoteright} tail of the 16S ribosomal RNA (the anti-SD sequence). In some cases, internal SD-like motifs in the coding region generate "programmed" ribosomal pauses that are beneficial for protein folding or accurate targeting. On the other hand, such pauses can also reduce protein production, generating purifying selection against internal SD-like motifs. This selection should be stronger in GC-rich genomes that are more likely to harbor the G-rich SD motif. However, the nature and consequences of selection acting on internal SD-like motifs within genomes and across species remains unclear. We analyzed the frequency of SD-like hexamers in the coding regions of 284 prokaryotes (277 with known anti-SD sequences and 7 without a typical SD mechanism). After accounting for GC content, we found that internal SD-like hexamers are avoided in 230 species, including three without a typical SD mechanism. The degree of avoidance was higher in GC-rich genomes, mesophiles, and N-terminal regions of genes. In contrast, 54 species either showed no signature of avoidance or were enriched in internal SD-like motifs. C-terminal gene regions were relatively enriched in SD-like hexamers, particularly for genes in operons or those followed closely by downstream genes. Together, our results suggest that the frequency of internal SD-like hexamers is governed by multiple factors including GC content and genome organization, and further empirical work is necessary to understand the evolution and functional roles of these motifs.

}, issn = {1759-6653}, doi = {10.1093/gbe/evw107}, author = {Diwan, Gaurav D and Agashe, Deepa} } @article {3547, title = {Large-Effect Beneficial Synonymous Mutations Mediate Rapid and Parallel Adaptation in a Bacterium.}, journal = {Mol Biol Evol}, year = {2016}, month = {2016 Feb 23}, abstract = {

Contrary to previous understanding, recent evidence indicates that synonymous codon changes may sometimes face strong selection. However, it remains difficult to generalize the nature, strength, and mechanism(s) of such selection. Previously, we showed that synonymous variants of a key enzyme-coding gene (fae) of Methylobacterium extorquens AM1 decreased enzyme production and reduced fitness dramatically. We now show that during laboratory evolution, these variants rapidly regained fitness via parallel yet variant-specific, highly beneficial point mutations in the N-terminal region of fae. These mutations (including four synonymous mutations) had weak but consistently positive impacts on transcript levels, enzyme production, or enzyme activity. However, none of the proposed mechanisms (including internal ribosome pause sites or mRNA structure) predicted the fitness impact of evolved or additional, engineered point mutations. This study shows that synonymous mutations can be fixed through strong positive selection, but the mechanism for their benefit varies depending on the local sequence context.

}, issn = {1537-1719}, doi = {10.1093/molbev/msw035}, author = {Agashe, Deepa and Sane, Mrudula and Phalnikar, Kruttika and Diwan, Gaurav D and Habibullah, Alefiyah and Martinez-Gomez, Norma Cecilia and Sahasrabuddhe, Vinaya and Polachek, William and Wang, Jue and Chubiz, Lon M and Marx, Christopher J} }