tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A. 2019 Sep 4. pii: 201907626. doi: 10.1073/pnas.1907626116. [Epub ahead of print]
[h=1]Many human RNA viruses show extraordinarily stringent selective constraints on protein evolution.[/h] Lin JJ[SUP]1[/SUP], Bhattacharjee MJ[SUP]1[/SUP], Yu CP[SUP]1[/SUP], Tseng YY[SUP]2[/SUP], Li WH[SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h] 1 Biodiversity Research Center, Academia Sinica, 11529 Taipei, Taiwan. 2 Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201; ytseng@wayne.edu whli@uchicago.edu. 3 Biodiversity Research Center, Academia Sinica, 11529 Taipei, Taiwan ytseng@wayne.edu whli@uchicago.edu. 4 Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637.
[h=3]Abstract[/h] How negative selection, positive selection, and population size contribute to the large variation in nucleotide substitution rates among RNA viruses remains unclear. Here, we studied the ratios of nonsynonymous-to-synonymous substitution rates (d [SUB]N[/SUB]/d [SUB]S[/SUB]) in protein-coding genes of human RNA and DNA viruses and mammals. Among the 21 RNA viruses studied, 18 showed a genome-average d [SUB]N[/SUB]/d [SUB]S[/SUB] from 0.01 to 0.10, indicating that over 90% of nonsynonymous mutations are eliminated by negative selection. Only HIV-1 showed a d [SUB]N[/SUB]/d [SUB]S[/SUB] (0.31) higher than that (0.22) in mammalian genes. By comparing the d [SUB]N[/SUB]/d [SUB]S[/SUB] values among genes in the same genome and among species or strains, we found that both positive selection and population size play significant roles in the d [SUB]N[/SUB]/d [SUB]S[/SUB] variation among genes and species. Indeed, even in flaviviruses and picornaviruses, which showed the lowest ratios among the 21 species studied, positive selection appears to have contributed significantly to d [SUB]N[/SUB]/d [SUB]S[/SUB] We found the view that positive selection occurs much more frequently in influenza A subtype H3N2 than subtype H1N1 holds only for the hemagglutinin and neuraminidase genes, but not for other genes. Moreover, we found no support for the view that vector-borne RNA viruses have lower d [SUB]N[/SUB]/d [SUB]S[/SUB] ratios than non-vector-borne viruses. In addition, we found a correlation between d [SUB]N[/SUB] and d [SUB]S[/SUB], implying a correlation between d [SUB]N[/SUB] and the mutation rate. Interestingly, only 2 of the 8 DNA viruses studied showed a d [SUB]N[/SUB]/d [SUB]S[/SUB] < 0.10, while 4 showed a d [SUB]N[/SUB]/d [SUB]S[/SUB] > 0.22. These observations increase our understanding of the mechanisms of RNA virus evolution.
[h=4]KEYWORDS:[/h] flaviviruses; influenza A viruses; picornaviruses; positive selection; selective constraints
PMID: 31484772 DOI: 10.1073/pnas.1907626116
[h=1]Many human RNA viruses show extraordinarily stringent selective constraints on protein evolution.[/h] Lin JJ[SUP]1[/SUP], Bhattacharjee MJ[SUP]1[/SUP], Yu CP[SUP]1[/SUP], Tseng YY[SUP]2[/SUP], Li WH[SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h] 1 Biodiversity Research Center, Academia Sinica, 11529 Taipei, Taiwan. 2 Center for Molecular Medicine and Genetics, School of Medicine, Wayne State University, Detroit, MI 48201; ytseng@wayne.edu whli@uchicago.edu. 3 Biodiversity Research Center, Academia Sinica, 11529 Taipei, Taiwan ytseng@wayne.edu whli@uchicago.edu. 4 Department of Ecology and Evolution, University of Chicago, Chicago, IL 60637.
[h=3]Abstract[/h] How negative selection, positive selection, and population size contribute to the large variation in nucleotide substitution rates among RNA viruses remains unclear. Here, we studied the ratios of nonsynonymous-to-synonymous substitution rates (d [SUB]N[/SUB]/d [SUB]S[/SUB]) in protein-coding genes of human RNA and DNA viruses and mammals. Among the 21 RNA viruses studied, 18 showed a genome-average d [SUB]N[/SUB]/d [SUB]S[/SUB] from 0.01 to 0.10, indicating that over 90% of nonsynonymous mutations are eliminated by negative selection. Only HIV-1 showed a d [SUB]N[/SUB]/d [SUB]S[/SUB] (0.31) higher than that (0.22) in mammalian genes. By comparing the d [SUB]N[/SUB]/d [SUB]S[/SUB] values among genes in the same genome and among species or strains, we found that both positive selection and population size play significant roles in the d [SUB]N[/SUB]/d [SUB]S[/SUB] variation among genes and species. Indeed, even in flaviviruses and picornaviruses, which showed the lowest ratios among the 21 species studied, positive selection appears to have contributed significantly to d [SUB]N[/SUB]/d [SUB]S[/SUB] We found the view that positive selection occurs much more frequently in influenza A subtype H3N2 than subtype H1N1 holds only for the hemagglutinin and neuraminidase genes, but not for other genes. Moreover, we found no support for the view that vector-borne RNA viruses have lower d [SUB]N[/SUB]/d [SUB]S[/SUB] ratios than non-vector-borne viruses. In addition, we found a correlation between d [SUB]N[/SUB] and d [SUB]S[/SUB], implying a correlation between d [SUB]N[/SUB] and the mutation rate. Interestingly, only 2 of the 8 DNA viruses studied showed a d [SUB]N[/SUB]/d [SUB]S[/SUB] < 0.10, while 4 showed a d [SUB]N[/SUB]/d [SUB]S[/SUB] > 0.22. These observations increase our understanding of the mechanisms of RNA virus evolution.
[h=4]KEYWORDS:[/h] flaviviruses; influenza A viruses; picornaviruses; positive selection; selective constraints
PMID: 31484772 DOI: 10.1073/pnas.1907626116