UCL: Emergence of Genomic Diversity & Recurrent Mutations in SARS-CoV-2

SARS-CoV-2 - Credit NIAID


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We've another genetic analysis of SARS-CoV-2 - the virus that causes COVID-19 - this time from researchers at University College London (UCL), that finds growing diversity among emerging pandemic virus.

Yesterday, in More COVID-19 (SARS-CoV-2) Mutation Reports, we looked at two reports on the G clade which emerged in Europe in February carrying the D614G mutation, and has become the dominant strain since.

As I mentioned yesterday, while all viruses mutate, most of those mutations either have no impact, or are detrimental to the virus's biological `fitness'. Only a few are likely to enhance its transmissibility, replication, or pathogenicity in humans.

While rare occurrence, we've seen these types of mutations crop up in other viruses in the past (see COVID-19 & The `M' Word). 

Although the SARS-CoV-2 virus emerged pretty much ready for prime time, there are subtle signs it may still be adapting to human hosts.  While granting that it is nearly impossible to predict the future trajectory of COVID-19, the authors of today's report write:

It is also possible that the population of SARS-CoV-2 will evolve into different lineages characterised by variable levels of virulence and transmissibility. However, despite existing phylogenetic structure (Rambaut et al., 2020), it is important to stress that there is no evidence for the evolution of distinct phenotypes in SARS-CoV-2 at this stage.

The study is both lengthy and highly technical, and so I've posted the abstract below, followed by a excerpts from a press release from UCL.  Both links will lead you to the full reports.

Emergence of genomic diversity and recurrent mutations in SARS-CoV-2

Lucyvan Dorpa, Mislav Acman, Damien Richard, Liam P.Shaw, Charlotte E.Ford,  Louise Ormond. Christopher J.Owen , Juanita Pang , Cedric C.S.Tan, Florencia A.T.Boshier, Arturo Torres Ortiz , François Balloux 
https://doi.org/10.1016/j.meegid.2020.104351

Highlights

• Phylogenetic estimates support that the COVID-2 pandemic started sometimes around 6 October 2019–11 December 2019, which corresponds to the time of the host-jump into humans

• The diversity of SARS-CoV-2 strains in many countries recapitulates its full global diversity, consistent with multiple introductions of the virus to regions throughout the world seeding local transmission events.

• 198 sites in the SARS-CoV-2 genome appear to have already undergone recurrent, independent mutations based on a large-scale analysis of public genome assemblies.

• Detected recurrent mutations may indicate ongoing adaptation of SARS-CoV-2 to its novel human host.

• Monitoring the build-up and patterns of genetic diversity in SARS-CoV-2 has potential to inform targets for drug and vaccine development.

Abstract

SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 52,020, and thousands of genomes have been sequenced since this date.

This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time.

Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host.

Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity.

By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome.

Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.

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The following press release from University College London provides a lay explanation of what this study found.


Mutations in SARS-CoV-2 offer insights into virus evolution

6 May 2020

By analysing virus genomes from over 7,500 people infected with Covid-19, a UCL-led research team has characterised patterns of diversity of SARS-CoV-2 virus genome, offering clues to direct drugs and vaccine targets.

The study, led by the UCL Genetics Institute, identified close to 200 recurrent genetic mutations in the virus, highlighting how it may be adapting and evolving to its human hosts.

Researchers found that a large proportion of the global genetic diversity of SARS-CoV-2 is found in all hardest-hit countries, suggesting extensive global transmission from early on in the epidemic and the absence of single ‘Patient Zeroes’ in most countries.

The findings, published today in Infection, Genetics and Evolution, also further establish that the virus only emerged recently in late 2019, before quickly spreading across the globe.

Scientists analysed the emergence of genomic diversity in SARS-CoV-2, the new coronavirus causing Covid-19, by screening the genomes of over 7,500 viruses from infected patients around the globe. They identified 198 mutations that appear to have independently occurred more than once, which may hold clues to how the virus is adapting.

Co-lead author Professor Francois Balloux (UCL Genetics Institute) said: “All viruses naturally mutate. Mutations in themselves are not a bad thing and there is nothing to suggest SARS-CoV-2 is mutating faster or slower than expected. So far we cannot say whether SARS-CoV-2 is becoming more or less lethal and contagious.”

The small genetic changes, or mutations, identified were not evenly distributed across the virus genome. As some parts of the genome had very few mutations, the researchers say those invariant parts of the virus could be better targets for drug and vaccine development.

“A major challenge to defeating viruses is that a vaccine or drug might no longer be effective if the virus has mutated. If we focus our efforts on parts of the virus that are less likely to mutate, we have a better chance of developing drugs that will be effective in the long run,” Professor Balloux explained.

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