Spontaneous mutations introduce uncertainty into COVID-19 control procedures and vaccine development. Here, we perform spatio-temporal analysis on intra-host single-nucleotide variations (iSNVs) in 402 clinical samples from 170 patients, which reveals an increase in genetic diversity over time post-symptoms onset within individual patients. Nonsynonymous mutations are over-represented in the pool of iSNVs, but underrepresent at the single nucleotide polymorphism (SNP) level, suggesting a two-step fitness selection process: a large number of nonsynonymous substitutions are generated within the host (positive selection), and these substitutions tend to be unfixed as SNPs in population (negative selection). Dynamic iSNVs changes in subpopulations of different gender, age, illness severity and viral shedding time displayed a varied fitness selection process among populations. Taken together, our study highlights iSNVs provide a mutational pool shaping the virus rapid global evolution.

Fuente: Cell Reports
Available online 16 December 2021, 110205