Reply to Sánchez-Pacheco et al., Chookajorn, and Mavian et al.: Explaining phylogenetic network analysis of SARS-CoV-2 genomes.

We calculated a phylogenetic analysis network of the 160 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) complete genomes submitted to the international Global Initiative on Sharing Avian Influenza Data (GISAID) database by early March 2020, to produce a snapshot of the beginning of the SARS-CoV-2 epidemic (1). Phylogenetic network analysis of human mitochondrial DNA and human Y chromosomes has been successful in revealing the prehistoric spread of Homo sapiens across the planet (2, 3), and we reasoned it would equally be a useful tool for reconstructing the mutational evolution of coronavirus genomes. Combining median-joining and Steiner network algorithms, we obtained a network visualizing the 288 most parsimonious trees simultaneously. Included in the dataset was the closest known nonhuman coronavirus, a bat coronavirus with more than 96% sequence similarity to the human virus. This bat coronavirus rooted the network in a cluster we have labeled “A,” from which a prominent cluster “B” and in turn a prominent cluster “C” derive. In these 160 genomes representing the initial phase of the epidemic, within China the ancestral A types are more common outside Wuhan rather than within Wuhan. We observe that documented transmission paths closely follow the order of mutations that is inferred by the network. The letter by Sanchez-Pacheco et al. (4) consists of a number of unsubstantiated statements with regard to coronavirus evolutionary analysis, and of methodological misunderstandings, as follows. Sanchez-Pacheco et al. (4) opine that a network does not reflect the important biological features thought to underlie viral evolution, such as recombination and horizontal gene transfer, making median-joining networks inappropriate in this setting. However, neither Sanchez-Pacheco et al. nor we in our PNAS paper (1) claim that recombination in the human coronavirus data has happened. It is therefore not clear why Sanchez-Pacheco et al. raise this point. In fact, … [↵][1]1To whom correspondence may be addressed. Email: pf223{at}cam.ac.uk. [1]: #xref-corresp-1-1