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Abstract:

Accessory proteins have diverse roles in coronavirus pathobiology. One of such proteins in SARS-CoV is encoded by the open reading frame 8 (ORF8). One of the most dramatic genomic changes observed in SARS-CoV isolated from patients during the peak of the pandemics was the acquisition of a characteristic 29-nucleotide deletion in ORF8. This deletion causes splitting of ORF8 into two smaller ORFs, namely ORF8a and ORF8b. Functional consequences of this event are not entirely clear. Here, we performed evolutionary analyses of ORF8a and ORF8b genes and found that in both cases the frequency of synonymous mutations was greater than that of nonsynonymous ones. These results suggest that ORF8a and ORF8b are under purifying selection, thus proteins translated from these ORFs are likely to be functionally important. This result echoes with the known excess of deletions in the ORF7a-ORF7b-ORF8 complex of accessory genes in SARS-CoV-2. A high frequency of deletions in this gene complex might reflect recurrent searches in “functional space” of various accessory protein combinations that may eventually produce more advantageous configurations of accessory proteins similar to the deletion in the SARS-CoV ORF8 gene.