The Kishony Mega-Plate Experiment, a Markov Process

A correct understanding of the DNA evolution of drug resistance is critical in developing strategies for suppressing and preventing this process. The Kishony Mega-Plate Experiment demonstrates this important phenomenon that occurs in the practice of medicine, that of the evolution of drug-resistance. The evolutionary process which the bacteria in this experiment are doing is called a Markov Process or Markov Chain. Understanding this process enables clinicians and researchers to predict the evolution of drug-resistance and develop strategies to prevent this process. This paper will show how to apply the Markov Chain model of DNA evolution to the Kishony Mega-Plate Experiment and why the experiment behaves the way it does by contrasting the Jukes-Cantor model of DNA evolution (a stationary model) with a modification of the JukesCantor model that makes it a non-stationary, non-equilibrium Markov Chain. The numerical behaviors of the stationary and non-stationary models are compared. What this analysis shows is that DNA evolution is a non-stationary, non-equilibrium process and that by using the correct non-stationary, non-equilibrium model that one can simulate and predict the behavior of real evolutionary examples and that these analytical tools can give the clinician guidance on how to use antimicrobial selection pressures for treating infectious diseases. This in turn can help reduce the numbers and costs of hospitalization for sepsis, pneumonia and other infectious diseases.

DNA evolution depends on differential methylation patterns in rat speciation

The fixation of phenotypes and underlying alleles is a typical evolutionary process in speciation. As the primary molecular basis of phenotypic plasticity, epigenetic mechanisms also play an essential role in maintaining phenotypes. However, whether and how DNA evolution was shaped by epigenetic alteration remains unknown, especially accompanied DNA fixation in speciation. We used sperm methylomes of three rat subspecies as epigenetic markers and screened out genomic regions that experienced distinct differential methylation. To obtain independent results, they were further filtrated according to genomic locations to guarantee that their evolutionary features were not interactively affected by nearby DMRs (differentially methylated regions) of other datasets. By analyzing intraspecies and interspecies phylogenetic relationships, we showed that, in the same genomic regions, the significantly accelerated DNA evolution only occurred in individuals or lineages that experienced differential methylation. Across the same genomes, differential methylation led to a significant increase of F only in lineage-specific DMRs and a significant increase of π in both individual-specific and lineage-specific DMRs. Correlations among methylation, π and F showed that it was methylation consistency rather than the absolute methylation difference that significantly influenced both π and F. The change of both π and DNA fixation depended on the degree of intraspecies methylation consistency. While the breakdown of methylation consistency facilitated the promotion of π, the maintenance of methylation consistency facilitated the acceleration of DNA fixation.