Yashraj Chavhan

As a postdoc in Peter Lind Lab at Umeå University, I have been working on two distinct topics:

1. The evolutionary transition from unicellularity to multicellularity was a key innovation in the history of life that paved the way for increased organismal complexity. Given scarce fossil evidence, experimental evolution has been an important tool to study this transition. However, most experimental evolution studies of multicellularity suffer from two blind spots. Although multicellularity originally evolved on Earth among bacteria, previous experimental evolution research has primarily used eukaryotes. Moreover, this research focuses on mutationally driven (and not environmentally induced) phenotypes. Addressing these blind spots, I have now shown that both Gram-negative and Gram-positive bacteria exhibit phenotypically plastic (i.e., environmentally induced) cell clustering. Under high salinity, they form elongated macroscopic clusters (length ~ 2 cm). However, under habitual salinity, such clusters disintegrate, and the bacteria exhibit a unicellular planktonic mode of growth.

Next, using experimental evolution with Escherichia coli, I showed that such ancestrally inducible clustering can be assimilated genetically: the evolved bacteria inherently grew as macroscopic multicellular clusters, even without environmental induction. I established that highly parallel mutations in genes linked to cell wall assembly were the genomic basis of the assimilated multicellularity. I also found that the wildtype ancestor showed plasticity at the level of single cells: spherical cells under high salinity, but rod-shaped cells under habitual salinity. While the ancestrally plastic multicellularity got assimilated genetically, the cell shape plasticity was either assimilated or reversed. Interestingly, a single mutation could genetically assimilate multicellularity by modulating plasticity at multiple levels of organization. This is the first-ever study to demonstrate how the evolution of plasticity at the level of single cells links to its evolution at the level of cell collectives. Moreover, it demonstrates that phenotypic plasticity can prime bacteria for evolving macroscopic multicellularity. The first manuscript on this work has been recently published in Nature Communications.

2. Using mutation biases to forecast the evolution of antibiotic resistance in the clinic: I have independently developed a new workflow to empirically determine mutation biases for antibiotic resistance. I have discovered a mutation hotspot for ciprofloxacin resistance in the opportunistic pathogen Pseudomonas aeruginosa, with a >276-fold higher mutation rate than expected. Incorporating this discovery yields successful quantitative forecasts of resistance evolution at the level of single base pairs. I recently presented a talk based on this work at the SMBE Everywhere conference organized by the Society for Molecular Biology and Evolution. We are currently writing its associated manuscript.