key: cord-0007221-mhm7r3qc
authors: Yi, Huiguang
title: 2019 novel coronavirus is undergoing active recombination
date: 2020-03-04
journal: Clin Infect Dis
DOI: 10.1093/cid/ciaa219
sha: ede06a957447db43f6707242c71b6810617ae622
doc_id: 7221
cord_uid: mhm7r3qc

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(shown as a pie chart node in Fig. 1 , see Tab. S1 for the accessions), then the network is constructed using the median join [4] method in popART [5] . We found the 2019-nCoV haplotype network has obvious characteristics of single origin from haplotype hap_011: first, the network is star-like, centralized on the haplotype hap_011; second, hap_011 has the largest sample size and majority of the samples are from Hubei province-where outbreak originated (Tab. S1); third, most of satellite haplotypes are also from Hubei (Fig. 1) ; fourth, the average collection dates of hap_011 (has 0 mutation relative to MN908947) is earlier than all other mutation groups (Fig. S1 ). The single origin of 2019-nCov indicates a persistent animal to human transmission is unlikely, otherwise, multiple nodes with above characteristics should be observed.

We found five haplotypes (hap_009, hap_017, hap_023, hap_048 and hap_050) forming loops ( Fig. 1) , which typically indicate existing of genetic recombination. However, in rare cases, loops can also be formed by recurring sequencing error or parallel/back mutations. Further examination of the differences pattern among the five haplotypes found three sets of recurrent differences: C29095T, G11083T and C8782T/T28144C (Fig. 1) , most of which are nonsynonymous changes except C29095T (Tab. S2). Such highly frequent recurrent differences looks extremely unlikely raised by rare events like recurring sequencing error/mutations. To quantify the significance of recombination over recurring sequencing error/mutations, Phi [6] and Max Chi-squared tests [7] in the software PhiPack [8] were performed. It showed p-values of 0.03 and 0.005 for Phi and Max Chi-squared, respectively, indicating the presence of recombinants in 2019-nCoV population. 3 Since all the haplotypes originate from hap_011, the formation mechanisms of the five haplotypes could be inferred as follow: First, hap_048 and hap_050 mutated from the common ancestry hap_011 independently, hap_009 then mutated from hap_050; next, hap_048 donated the genome region harboring 11083T to hap_050 generated the recombinant hap_017; similarly, hap_048 or hap_017 donated the same region to hap_009 generated the recombinant hap_023 susceptibility directly from other strains [12, 13] ; the adaptability of 2019-nCoV to human immune system might be significantly strengthened through genetic recombination; the accuracy of diagnosis based on serologic and molecular biology assays might be compromised [14] ; and the transmission tracking based on phylogenetics tree could be misleading since the topology of mutation route is a network rather than a tree.

We think the communities of infectious disease physicians and disease control specialists should arouse particular concerns about this finding and its potential implications. And we expect this 4 findings may provide a valuable perspective for strategies design for secondary transmission prevention and drug treatments for 2019-nCoV pneumonia. Each haplotype node is represent by a pie chart, with size indicating the sample size (Tab S1), and colors indicating collection regions. Each hatch mark along the edge corresponds to a mutation between the two haplotypes linked. The mutation notation along a loop edge shows the position and nucleotide status change between the two haplotypes linked. 

Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. 2020. 2. Confirmed 2019-nCoV Cases Globally Global Map

Real-time, portable genome sequencing for Ebola surveillance

Median-joining networks for inferring intraspecific phylogenies

Full-feature software for haplotype network construction

A Simple and Robust Statistical Test for Detecting the Presence of Recombination

Analyzing the mosaic structure of genes

PhiPack: PHI test and other tests of recombination

nCoV's relationship to bat coronaviruses & recombination signals (no snakes) -no evidence the 2019-nCoV lineage is recombinant

Full-genome evolutionary analysis of the novel corona virus (2019-nCoV) rejects the hypothesis of emergence as a result of a recent recombination event

Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

Possible involvement of cell fusion and viral recombination in generation of human immunodeficiency virus variants that display dual resistance to AZT and 3TC

Recombination leads to the rapid emergence of HIV-1 dually resistant mutants under selective drug pressure

Human immunodeficiency virus superinfection and recombination: current state of knowledge and potential clinical consequences

We acknowledge the authors and the originating and submitting laboratories of the nucleotide sequences from BetaCoV2019-2020 of GISAID EpiFluTM Database (9 Feb 2020, 84 isolates).

All authors: No reported conflicts.