A mutation in an RNA-dependent RNA polymerase (RdRp) is important to note because of its major role in viral replication and transcription, leading to its tendency to be used as a target in antiviral treatment. A study found two different types of mutations in an RdRp of SARS-CoV-2. One is a silent mutation found in the UK on February 9th, 2020, while a different mutation was first reported in Italy on February 20th, 2020. Since the introduction of a mutation of RdRp in Italy, there was an increase in the number of mutations of the virus in the region. By dividing genomes into two groups: one group with the RdRp mutation and one without, it was shown that the group with the RdRp mutation showed a higher frequency of mutations compared to the group without the RdRp mutation. 

Mutation in RNA-dependent RNA polymerase of SARS-CoV-2 in Europe

D614G is known to give a fitness advantage to the SARS-CoV-2 virus. In the Middle East and North Africa (MENA), a phylogenic analysis was done on 553 MENA sequences. In the 553 sequences, the S gene mutations were found to be D614G=435, Q677H=8, and V6F=5. This shows a vast increase in the D614G mutations, from 63.0% in February, 2020 to 98.5% in June, 2020. Large clusters of Bayesian analyses determined the average evolutionary rate for SARS-CoV-2 to be about 6.5 x 10-3 substitutions/site/year in MENA.

Mutation in D614G of SARS-CoV-2 in the Middle East and North Africa

University of Michigan - Ann Arbor

University of California, Davis

The type and number of mutations can differ based on region. SARS-CoV-2 in Europe and North America were found to have higher rates and variety of mutations compared to regions closer to the origin of the virus like Asia. Differences in mutations per region increased overtime outside of Asia. 

Mutations of SARS-CoV-2 can differ by Region

Occurence of mutations of SARS-CoV-2 by Region

SARS-CoV-2 mutation frequency in different geographic areas. Eight novel recurrent hotspots mutations (namely 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881) and 5 hotspots already reported in literature (namely 3036, 8782, 11083, 28144 and 26143) were subdivided into 4 geographic areas: Asia (n = 71), Oceania (n = 15), Europe (n = 101), North America (n = 33). The mutation frequency was estimated for each of them, by normalizing the number of genomes carrying a given mutation in a geographic area, by the overall number of retrieved genomes per geographic area; the graph shows the cumulative mutation frequency of all given mutations present in each geographic area. Mutation locations in viral genes are reported in the legend as well as the proteins (i.e. non-structural protein, nsp) presenting these mutations. The figure shows that genomes from European and North American patients present an increase in mutation frequency compared to Asia. It is also possible to observe that Europe and North America show a differential pattern of mutations: mutation 14408 (red), 23403 (black), 28881 (electric blue) and 26143 (light green) are present mostly in Europe, whereas 18060 (pink), 17857 (purple) and 17746 (light blue) are present mostly in North America

Fig 1. SARS-CoV-2 mutation frequency in different geographic areas

SARS-CoV-2 Mutation occurrence over time divided per geographic area. Eight novel recurrent hotspots mutations (namely 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881) and 5 hotspots already reported in literature (namely 3036, 8782, 11083, 28144 and 26143) were subdivided first into 5 period subgroups: December 2019 (n = 5), 1st–15th Jan. 2020 (n = 15), 16th–31st Jan 2020 (n = 52), 1st–15th Feb 2020 (n = 13), 16th–29th Feb 2020 (n = 55) and 1st–13th Mar 2020 (n = 80). Next, for each time group, a further subclassification per geographic area (Asia, Oceania, Europe and North America) was performed (number of genomes in each area are reported in the figure inset). The number of mutations in each area was normalized by the number of genomes analyzed for each period of time. This figure shows that mutation frequency increases over time during viral spread out of Asia. No mutations were observed in the Asian genomes analyzed in December 2019. In the time group of February 16th–29th, a defined cluster of mutations emerged in Europe; in March 1st–13th, a different cluster of mutations emerged in North America

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