Recombination and lineage-specific mutations led to the emergence of SARS-CoV-2

Juan Angel Patino-Galindo; Ioan Filip; Mohammed AlQuraishi; Raul Rabadan

Sliding window analysis was performed in order to test for enrichment of recombination breakpoints (including both start and end breakpoints) along the viral genome in the following settings: 1) all beta-CoV recombinations; 2) recombinations within non-human lineages for Beta-CoV; 2) all MERS-CoV recombinations; and 3) both human-specific and non-human MERS-CoV lineage recombinations separately. There were too few human-specific recombinations in beta-CoV for in-depth analysis. For beta-CoV analyses, the SARS-CoV genomic coordinates were used as reference (accession NC_004718), whereas for MERS CoVs, we used a MERS-CoV sequence (accession NC_019843) as reference. Windows of 800 nucleotides were selected and binomial tests for the number of breakpoints in each window were performed under the null hypothesis that recombination breakpoints are distributed uniformly along the genome. Given the co-dependence structure of our statistical tests, adjustments were performed using the Benjamini-Yekutieli (BY) procedure 34 which provides a conservative multiple hypothesis correction that applies in arbitrary dependence conditions. For statistical significance, we chose 5% BY false discovery rate (FDR). Our discoveries are valid with different choices of window length, provided the window length is sensitive to the scale CoV proteins and the length of specific domains such as the RBD in the Spike gene.