Asp, M. E. | Search bioRxiv

bioRxiv2023

Stochastic bounds of aggregation dynamics distinguish near-wild-type from wild-type strains in social bacteria

The genotype-to-phenotype problem (G2P) for multicellular development asks how genetic inputs control collective phenotypic outputs. It is a difficult problem even to observe. On the genotype side, the phenotypic impact of mutation is often subtle due at least partly to gene redundancy and myriad other factors. On the phenotype side, biological and even technical developmental replicates can display significant phenotypic variation due at least in part to stochasticity, again with other factors. We attempt to partially resolve the G2P inputs and outputs from the obfuscating effects of factors like redundancy and stochasticity. As a model organism, we selected the biofilm-forming species Myxococcus xanthus, a motile self-organizing bacterium that forms three-dimensional cell aggregates that grow and mature into spore-filled fruiting bodies when under starvation stress. We developed data acquisition tools and analysis and visualization methods that can produce a topological map of M. xanthus development. We demonstrate that even subtle effects on developmental dynamics caused by mutation can be identified, discriminated, characterized, and given statistical significance.

biophysics↗

bioRxiv2022

Phenotypic similarity is a measure of functional redundancy within homologous gene families

Robustness to the impact of mutation can mitigate phenotypes that have the potential to inform gene function. This robustness is often encoded into the genome through gene duplication, among other mechanisms. Duplication is a source of structurally similar genes that can retain some functional overlap as they diverge, and as such contribute to functional redundancy in the face of mutation. While redundancies have been explored in groups of two or three paralogs by generating double and triple mutants, it is unclear to what extent larger homologous gene families contribute to robustness through functional redundancy. Here, we used phenotypic similarity as an indicator of functional redundancy to explore the extent to which homologous gene families contribute to redundancy in function. We hypothesize that, since functional redundancy is more likely to occur within gene families where genes are structurally similar, mutant strains within the same gene families would be more phenotypically similar. We generated 265 single-gene disruptions in four homologous gene families of Myxococcus xanthus, used time-lapse microscopy to generate time series of multicellular development, and developed an image analysis pipeline to compare phenotypic characteristics among different strains. We show that mutant strains cluster by gene family in the phenotypic feature space with principal component analysis, demonstrating that families of homologs can contain extensive functional redundancy networks.

systems biology↗