Deciphering the SSR incidences across viral members of Coronaviridae family

Abstract

Presence of Simple Sequence Repeats (SSRs), both in genic and intergenic regions, have been widely studied in eukaryotes, prokaryotes, and viruses. In the current study, we undertook a survey to analyze the frequency and distribution of microsatellites or SSRs in multiple genomes of Coronaviridae members. We successfully identified 919 SSRs with length≥12 bp across 55 reference genomes majority of which (838 S SRs) were found abundant in genic regions. The in-silico analysis further identified the preferential abundance of hexameric SSRs than any other size-based motif class. Our analysis shows that the genome size and GC content of the genome had a weak influence on SSR frequency and density. However, we find a positive correlation of SSRs GC content with genomic GC content. We also report relatively low abundances of all theoretically possible 501 repeat motif classes in all the genomes of Coronaviridae . The majority of SSRs were AT-rich. Overall, we see an underrepresentation of SSRs across the genomes of Coronaviridae . Besides, our integrative study highlights the presence of SSRs in ORF1ab (nsp3, nsp4, nsp5A_3CLpro and nsp5B_3CLpro, nsp6, nsp10, nsp12, nsp13, & nsp15 domains), S, ORF3a, ORF7a, N & 3′ UTR regions of SARS-CoV-2 and harbours multiple mutations (3′UTR and ORF1ab SSRs serving as major mutational hotspots). This indicates the genic SSRs are under selection pressure against mutations that might alter the reading frame and at the same time responsible for rapid protein evolution. Our preliminary results indicate the significance of the limited repertoire of SSRs in the genomes of Coronaviridae.

Mining and analysis of microsatellites in human coronavirus genomes using the in-house built Java pipeline

“…The incidence of SSRs was insignificant but positively correlated with genome size (R 2 = 0.45, p > 0.05). Similarly, SSRs relative abundance R 2 = 0.18, p > 0.05, SSRs relative density R 2 = 0.23, and p > 0.05 were found to be insignificant but positively correlated with genome size; these results are in line with the study performed in deciphering the SSRs incidences across viral members of Coronaviridae family [38]. The cSSR number (R 2 = 0.008, p > 0.05), cSSR relative abundance (R 2 = 0.004, p > 0.05), cSSR relative density (R 2 = 0.002, p > 0.05) and cSSR % (R 2 = 0.004, p > 0.05) were found to be insignificant but positively correlated with genome size.…”

“…NC_006577.2. Overall, in our study, it has been observed that HKU1 is showing a slightly different pattern in SSRs and cSSR abundance per kb and consequently in relative abundance, density and GC % content; such a pattern has also been highlighted in earlier studies in screening microsatellites in 55 Coronaviridae genomes [38], and it is among the top four strains found to be infecting human beings.…”

Two short low complexity regions (LCRs) are hallmark sequences of the Delta SARS-CoV-2 variant spike protein

“…Viral SSRs are present in both RNA- and DNA viruses, including DNA mycobacteriophages 14 , economically relevant plant viruses such as potyviruses 16 , tobamoviruses 17 , and geminiviruses 18 , as well as in medically important viruses like herpesviruses 19 , HIV-1 20 and filoviruses 21 . More recently, several SSRs rich in hexameric repeats have been identified in the SARS-CoV-2 genome 22 , 23 , which appear to be more prevalent in the ORF1ab, S, ORF3a, N and ORF7a of the SARS-CoV-2 genic regions 23 .…”

Two Short Low Complexity Regions (LCRs) are Hallmark Sequences of the Delta SARS-CoV- 2 Variant Spike Protein

“…Viral SSRs are present in both RNA-and DNA viruses, including DNA mycobacteriophages 13 , economically relevant plant viruses such as potyviruses 16 , tobamoviruses 17 and geminiviruses 18 , as well as in medically important viruses like herpesviruses 19 , HIV-1 20 and loviruses 21 . More recently, several SSRs rich in hexameric repeats have been identi ed in the SARS-CoV-2 genome 22,23 . They appear to be more prevalent in the ORF1ab, S, ORF3a, N and ORF7a of the SARS-CoV-2 genic regions 23 , which opens the possibility that these regions may exhibit a trend towards greater genetic variability 10,22,23 .…”

“…More recently, several SSRs rich in hexameric repeats have been identi ed in the SARS-CoV-2 genome 22,23 . They appear to be more prevalent in the ORF1ab, S, ORF3a, N and ORF7a of the SARS-CoV-2 genic regions 23 , which opens the possibility that these regions may exhibit a trend towards greater genetic variability 10,22,23 . In this work, we report the conservation and variability of LCRs in several SARS-CoV-2 variants of concern (VOC) and interest (VOI) using comparative proteomics and protein structure analyses.…”