Biology subjects

Rohan Maddamsetti

Publications and source records attributed to Rohan Maddamsetti.

4 recordsLinked to original sources

bioRxiv2016

Core Genes Evolve Rapidly in the Long-term Evolution Experiment with Escherichia coli

Bacteria can evolve rapidly under positive selection owing to their vast numbers, allowing their genes to diversify by adapting to different environments. We asked whether the same genes that are fast evolving in the long-term evolution experiment with Escherichia coli (LTEE) have also diversified extensively in nature. We identified ~2000 core genes shared among 60 E. coli strains. During the LTEE, core genes accumulated significantly more nonsynonymous mutations than flexible (i.e., noncore) genes. Furthermore, core genes under positive selection in the LTEE are more conserved in nature than the average core gene. In some cases, adaptive mutations appear to fine-tune protein functions, rather than merely knocking them out. The LTEE conditions are novel for E. coli, at least in relation to the long sweep of its evolution in nature. The constancy and simplicity of the environment likely favor the complete loss of some unused functions and the fine-tuning of others.\n\nCompeting Interests StatementWe, the authors, declare that we have no conflicts of interest.

Evolutionary Biology↗

bioRxiv2015

Sustained fitness gains and variability in fitness trajectories in the long-term evolution experiment with Escherichia coli

Many populations live in environments subject to frequent biotic and abiotic changes. Nonetheless, it is interesting to ask whether an evolving populations mean fitness can increase indefinitely, and potentially without any limit, even in a constant environment. A recent study showed that fitness trajectories of Escherichia coli populations over 50,000 generations were better described by a power-law model than by a hyperbolic model. According to the power-law model, the rate of fitness gain declines over time but fitness has no upper limit, whereas the hyperbolic model implies a hard limit. Here, we examine whether the previously estimated power-law model predicts the fitness trajectory for an additional 10,000 generations. To that end, we conducted more than 1100 new competitive fitness assays. Consistent with the previous study, the power-law model fits the new data better than the hyperbolic model. We also analysed the variability in fitness among populations, finding subtle, but significant, heterogeneity in mean fitness. Some, but not all, of this variation reflects differences in mutation rate that evolved over time. Taken together, our results imply that both adaptation and divergence can continue indefinitely-- or at least for a long time--even in a constant environment.

Evolutionary Biology↗

bioRxiv2015

Haplotype-phased synthetic long reads from short-read sequencing

Next-generation DNA sequencing has revolutionized the study of biology. However, the short read lengths of the dominant instruments complicate assembly of complex genomes and haplotype phasing of mixtures of similar sequences. Here we demonstrate a method to reconstruct the sequences of individual nucleic acid molecules up to 11.6 kilobases in length from short (150-bp) reads. We show that our method can construct 99.97%-accurate synthetic reads from bacterial, plant, and animal genomic samples, full-length mRNA sequences from human cancer cell lines, and individual HIV env gene variants from a mixture. The preparation of multiple samples can be multiplexed into a single tube, further reducing effort and cost relative to competing approaches. Our approach generates sequencing libraries in three days from less than one microgram of DNA in a single-tube format without custom equipment or specialized expertise.

Genomics↗

bioRxiv2015

Adaptation, Clonal Interference, and Frequency-Dependent Interactions in a Long-Term Evolution Experiment with Escherichia coli

Twelve replicate populations of Escherichia coli have been evolving in the laboratory for more than 25 years and 60,000 generations. We analyzed bacteria from whole-population samples frozen every 500 generations through 20,000 generations for one well-studied population, called Ara-1. By tracking 42 known mutations in these samples, we reconstructed the history of this populations genotypic evolution over this period. The evolutionary dynamics of Ara-1 show strong evidence of selective sweeps as well as clonal interference between competing lineages bearing different beneficial mutations. In some cases, sets of several mutations approached fixation simultaneously, often conveying no information about their order of origination; we present several possible explanations for the existence of these mutational cohorts. Against a backdrop of rapid selective sweeps both earlier and later, we found that two clades coexisted for over 6000 generations before one drove the other extinct. In that time, at least nine mutations arose in the clade that prevailed. We found evidence that the clades evolved a frequency-dependent interaction, which prevented the competitive exclusion of either clade, but which eventually collapsed as beneficial mutations accumulated in the clade that prevailed. Clonal interference and frequency dependence can occur even in the simplest microbial populations. Furthermore, frequency dependence may generate dynamics that extend the period of coexistence that would otherwise be sustained by clonal interference alone.

Evolutionary Biology↗