A theoretical exploration of the origin and early evolution of a pandemic

A virus that can cause a global pandemic must be highly adaptive to human conditions.Such adaptation is not likely to have emerged suddenly but,instead,may have evolved step by step with each step favored by natural selection.It is thus necessary to develop a theory about the origin in order to guide the search.Here,we propose such a model whereby evolution occurs in both the virus and the hosts(where the evolution is somatic;i.e.,in the immune system).The hosts comprise three groups–the wild animal hosts,the nearby human population,and farther-away human populations.The theory suggests that the conditions under which the pandemic has initially evolved are:(i)an abundance of wild animals in the place of origin(PL_(0));(ii)a nearby human population of low density;(iii)frequent and long-term animal-human contacts to permit step-by-step evolution;and(iv)a level of herd immunity in the animal and human hosts.In this model,the evolving virus may have regularly spread out of PL_(0) although such invasions often fail,leaving sporadic cases of early infections.The place of the first epidemic(PL_(1)),where humans are immunologically naïve to the virus,is likely a distance away from PL_(0).Finally,this current model is only a first attempt and more theoretical models can be expected to guide the search for the origin of SARS-CoV-2.

On the origin of SARS-CoV-2——The blind watchmaker argument

In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more extensive.By the blind watchmaker argument,such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.

Dynamic global analysis of transcription reveals the role of mi RNAs in synergistic stabilization of gene expression

Buffering exogenous perturbation is crucial to maintain transcriptional homeostasis during development.While mi RNAs have been speculated to play a role in stability maintenance, previous studies seeking to check this conjecture focused on measurements of transcript levels at steady state or involved individual mi RNA targets. We measured whole-genome expression dynamics by introducing a transient perturbation and establishing a perturbation and recovery system in Drosophila larvae. We inhibited all transcription and assayed transcriptomes at several time points during recovery from inhibition. We performed these experiments in the wild type and mi RNA-deficient genetic backgrounds. Consistent with theories about mi RNAs’ function in stabilizing the transcriptome, we find that attenuating mi RNA expression leads to weak impairment in degradation of targets but strong destabilization of target genes when transcription is re-activated. We further fitted a model that captures the essential aspects of transcription dynamics in our experiments and found that the mi RNA target transcripts uniformly overshoot the original steady state as they recover from a general inhibition of transcription if global mi RNA levels are reduced. Collectively, our results provide experimental evidence for the idea that mi RNAs act cumulatively to stabilize the transcriptional regulatory network. We therefore found a promising approach to assess the effect of these molecules on transcription dynamics.