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Highlights We describe 11 major mutation events which defined five major clades (G 614 , S 84 , V 251 , I 378 and D 392 ) of globally-circulating viral populations. We have successfully developed a multiplexed sequencing-based, rapid genotyping protocol for high-throughput classification of major clade types of SARS-CoV-2 in clinical samples. Several nonsynonymous mutations in the spike protein may have functional consequences: the G clade–defining mutation D614 G located in subdomain 1; the V367 F, G476S and V483A are localised in the receptor binding domain (RBD) of the spike protein.

24We describe fifteen major mutation events from 2,058 high-quality SARS-CoV-2 25 genomes deposited up to March 31 st , 2020. These events define five major clades (G, I, S, 26 D and V) of globally-circulating viral populations, representing 85.7% of all sequenced 27 cases, which we can identify using a 10 nucleotide genetic classifier or barcode. We applied 28 this barcode to 4,000 additional genomes deposited between March 31 st and April 15 th and 29 classified successfully 95.6% of the clades demonstrating the utility of this approach. An 30 analysis of amino acid variation in SARS-CoV-2 ORFs provided evidence of substitution 31 events in the viral proteins involved in both host-entry and genome replication. The 32 systematic monitoring of dynamic changes in the SARS-CoV-2 genomes of circulating 33 virus populations over time can guide therapeutic and prophylactic strategies to manage 34 and contain the virus and, also, with available efficacious antivirals and vaccines, aid in the 35 monitoring of circulating genetic diversity as we proceed towards elimination of the agent. 36

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