Genomic variance of the 2019-nCoV coronavirus

Abstract

There is a rising global concern for the recently emerged novel coronavirus (2019-nCoV). Full genomic sequences have been released by the worldwide scientific community in the last few weeks to understand the evolutionary origin and molecular characteristics of this virus. Taking advantage of all the genomic information currently available, we constructed a phylogenetic tree including also representatives of other coronaviridae, such as Bat coronavirus (BCoV) and severe acute respiratory syndrome. We confirm high sequence similarity (>99%) between all sequenced 2019-nCoVs genomes available, with the closest BCoV sequence sharing 96.2% sequence identity, confirming the notion of a zoonotic origin of 2019-nCoV. Despite the low heterogeneity of the 2019-nCoV genomes, we could identify at least two hypervariable genomic hotspots, one of which is responsible for a Serine/Leucine variation in the viral ORF8-encoded protein. Finally, we perform a full proteomic comparison with other coronaviridae, identifying key aminoacidic differences to be considered for antiviral strategies deriving from previous anti-coronavirus approaches.

Keywords: CLUSTAL analysis; biostatistics & bioinformatics; coronavirus; data visualization; virus classification.

Figure 1

Phylogenetic tree of all the 2019‐nCov sequences available at 02‐Feb‐2020 (branches shown in blue), plus six Bat coronavirus sequences (default black, as they are split in multiple taxa), six human SARS (green) and two MERS (orange). The percentage of bootstraps supporting each branch is reported. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. MERS, Middle Eastern respiratory syndrome; SARS, severe acute respiratory syndrome

Figure 2

Categorical principal component analysis of the projected variance in the entire coronaviridae genome dataset considered in this study (A) and in the 2019‐nCoV subset only (B). Human 2019‐nCoV are shown as blue circles, other genomes as grey diamonds

Figure 3

Variability within 54 2019‐nCoV full genomic sequences. A, location of major structural protein‐encoding genes (red boxes; S = Spike protein, E = Envelope protein, M = Membrane protein, N = Nucleocapsid protein) and accessory protein ORFs (blue boxes) on the meta‐genomic sequence derived from the MSA of all genomes. B, Shannon entropy values across genomic locations. The two coordinates with the highest entropy (excluding the 5′ and 3′ highly variable UnTranslated regions) are indicated. C, Zoom‐in of the MSA describing the two most variable locations in the core genome, in the ORF1ab (left) and in ORF8 (right). MSA, multiple sequence alignment

Figure 4

A, MSA of the coronavirus proteins encoded by ORF8 in representative sequences for the 2019‐nCoV (Wuhan), BCoVs (Bat SARS‐like and Bat SARS) and SARS viruses. B, Alignment of ORF8‐L and ORF8‐S, two isoforms varying at amino acid position 84 (indicated by a red dot). The diagram shows in larger blue the Globplot‐predicted intrinsically disordered regions in the two isoforms. C, MSA of the coronavirus Nucleocapside proteins. MSA, multiple sequence alignment