LONDON, ENGLAND - DECEMBER 19: Britain's Prime Minister Boris Johnson speaks during a news ... [+]
On Saturday, Prime Minister Boris Johnson announced a highly restrictive lockdown to affect one-third of England’s population, including most of southeast England and London. The lockdown has been widely reported including in the New York Times, Washington Post, and by Reuters.
Here I look at some of the science behind this decision. I’ve written about molecular epidemiology before. This is another example of the deep insights that can be provided by genomic analysis.
The key finding driving the British lockdown appears to be the rapid increase in the number of cases represented by a specific evolutionary branch of SARS-CoV-2, the virus that causes Covid-19. The lineage has been named B.1.1.7 by the COVID-19 Genomics Consortium UK. A report published online in the blog virological.org co-authored by ten leading experts in viral evolution explains the latest findings. Highlights include:
This lineage has been around for a while
Patient specimens in Lineage B.1.1.7 were first collected in late September.
The lineage is monophyletic
This means it almost certainly originated in a single person. The original blog post has an interesting commentary on this, including the conjecture that the new lineage arose in a person who was chronically infected.
There are seventeen non-synonymous mutations or deletions
These are the potentially important mutations. That’s a lot of mutations to happen all at the same time. For background, the genetic code for SARS-CoV-2 is contained in its RNA. RNA is a “macromolecule” made up of nucleotides, each of which itself consists of a molecule of the sugar ribose, a phosphate group, and a nitrogen-containing “base”. In the case of SARS-CoV-2, the genome comprises a chain of 29,881 nucleotides. This sequence of nucleotides is the blueprint for sequences of amino acids that are the building blocks of all the pieces that go into making a virus particle. There is some redundancy in the genetic code so that some mutations don’t change the sequence of amino acids, the so-called “synonymous” mutations, while others do, i.e. the “non-synonymous” ones. Synonymous mutations are like having multiple sets of blueprints that lead to the same building. But non-synonymous mutations result in actual changes to the building materials. Here we have seventeen different changes to the virus that occurred all at once.
Eight of these important mutations are on the “S” gene
The S gene codes for a protein called spike. The spike protein is essential for the transmission of SARS-CoV-2. It is found on the surface of the virus particle and has a feature called the receptor binding domain. When the receptor binding domain encounters an enzyme, called ACE2, that is embedded in the membrane of a host cell, then another enzyme, called TM protease serine 2 (TMPRSS2), allows the virus into the cell.
Possibly the most important of these mutations is one known as N501Y
The nomenclature N501Y means that mutations in the new variant cause the amino acid at site 501 to become Tyrosine (symbol Y), whereas earlier genotypes had coded for Asparagine (symbol N). This amino acid provides one of just six points of contact with the receptor binding domain. This means that the N501Y mutation can affect how readily the virus gets into human cells. The mutation N501Y has been shown experimentally to cause SARS-CoV-2 to more readily infect mice. It has also arisen on several independent occasions, including in South Africa, as explained by evolutionary virologist Emma Hodcroft from the University of Basel.
The new lineage, including all 17 major mutations, has grown very rapidly in Britain over the last six weeks
The virological.org report says only that the B.1.1.7 lineage “has been growing rapidly over the past 4 weeks”. But, analysis on nextstrain.org suggests its rise to dominance in the UK began even earlier, in late October or early November, and happened really fast. According to the nextstrain analysis, this mutation is now found in more than 75% of samples collected in the UK.
The B.1.1.7 lineage has now also spread to other places
According to virological.org, roughly one-third of genotypes in the B.1.1.7 lineage are from Kent (a county in England adjacent to London), one third from London, and one third from elsewhere in Britain, including both Scotland and Wales. Besides this, Hodcroft reports that the lineage has been detected in Denmark and Australia, too.
If it is in these places, it is almost certainly circulating elsewhere in the world undetected.
What does this mean for the Covid-19 pandemic?
The rapid expansion of the B.1.1.7 lineage of SARS-CoV-2 is an interesting phenomenon that must have an explanation. Most likely, it has some kind of evolutionary advantage compared to other genotypes. The fact that the mutation N501Y makes SARS-CoV-2 more transmissible in mice suggests that this evolutionary advantage might have something to do with the virus’s ability to infect host cells, although this hasn’t actually been established yet. This could be epidemiologically important, for instance if it results in a reduction in the infectious dose. Likewise, there is no evidence yet concerning effects on disease severity one way or the other.
Given the close connections between the UK and many other countries, including the US, it is to be expected that this mutation will spread to other parts of the world. We should be vigilant.
