13 Aug 2023

There are lots of papers this week, buckle up

Predicting evolutionary outcomes through the probability of accessing sequence variants. Thanks Sarah for sharing this one! This is such a simple but important idea. Essentially, evolution follows not only the contours of the fitness landscape but also the “genotype-accessibility landscape”, which is shaped by stuff like codon bias and biochemical mechanisms of mutation changing the likelihoods of some mutations. They look at some examples of this in fu. https://www.science.org/doi/full/10.1126/sciadv.ade2903

 

Purifying selection and adaptive evolution proximate to the zoonosis of SARS-CoV-1 and SARS-CoV-2. These folks do some population genetics archaeology to try to put together what was happening with the genomes of SARS-CoV-1 and SARS-CoV-2 around the time they jumped into humans. They find most things are under purifying selection (which is generally the case with viruses as they “live on the (evolutionary) edge”. It’s interesting to note this is true of SPIKE,; I would’ve assumed there would be some pre-adaptation that makes zoonosis easier based on ACE2 binding, but looks like that wasn’t the case. Even more interesting is the fact that the genes that did show some signs of adaptation were non-structural proteins involved in replication and MHC modulation. This suggests the barrier that successful zoonotic pathogens need to jump during zoonosis is not so much cell entry as thwarting immunity within the cell—not what I would expect at all. Might be zoonotic pathogen survivor bias though. https://www.biorxiv.org/content/10.1101/2023.08.07.552269v1

 

Evolutionary safety of lethal mutagenesis driven by antiviral treatment. I kind of hate sharing a Martin Nowak (of Epstein fame) paper, but I also think of the trainees. These folks work out the math to determine when a mutagenesis-inducing drug is actually increasing pathogen evolution at the population level. They find that the covid drug molnupiravir is “narrowly evolutionarily safe”, which, given uncertainty in parameters and variability in usage, is too close to not being safe in my book. https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3002214 , tweetorial here: https://twitter.com/GabrielaL3001/status/1689242610613813248

 

The minimal intrinsic stochasticity of constitutively expressed eukaryotic genes is sub-Poissonian. Not evolution, but interesting to think about variability in gene expression as a trait affecting fitness. The authors find that for some genes, expression noise is below what would be expected from a normal Poisson process dictating mRNA copy number. Instead, cranking up and tightening regulation of production and degradation can lead to variability below what you’d expect for Poisson, which can be crucial for certain genes. Since directional selection is easier to think about, we often forget how many resources organisms spend on regulation that doesn’t modify the mean value of a trait. Regulation is fitness (in fact, see the next paper). https://www.science.org/doi/10.1126/sciadv.adh5138

 

Segregational drift hinders the evolution of antibiotic resistance on polyploid replicons. A cool instance of how tight regulation of copy number can have important evolutionary consequences. The authors use theory and experiments to show how the spread of antibiotic resistance genes on multi-copy elements (e.g. plasmids) can be slowed or reversed due to drift effects in the segregation of these elements during cell division. https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1010829

 

Cooperative assembly confers regulatory specificity and long-term genetic circuit stability. This is also not directly evolution, but has some important implications related to the fitness costs of regulation. These people are interested in building synthetic regulatory circuits, which have the problem of being ditched by the cells since their upkeep represents a fitness cost. They find (among many other things) that those fitness costs are usually due to off-target effects of unspecific regulation, and that they can reduce those fitness costs and increase the evolutionary stability of constructs by using multi-part regulators with higher specificity. Another example of how greater complexity and resource expenditure ends up “costing less” in fitness for an organism. https://www.sciencedirect.com/science/article/pii/S0092867423007456

 

Virus-assisted directed evolution of biomolecules. Exactly what it sounds like, cool review. https://www.sciencedirect.com/science/article/abs/pii/S1367593123001138

 

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