Nextstrain update on SARS-CoV-2

“Changes in viral genomes over time are normal

“SARS-CoV-2, the virus that causes the disease COVID-19, is a coronavirus. Like other coronaviruses, SARS-CoV-2 has a genome encoded in RNA (rather than DNA).

“Viruses infect cells because they need to borrow cellular machinery to replicate. For RNA viruses, this process is quite error-prone, as most RNA polymerases (the molecular machines that make copies of RNA) aren’t able to proofread and correct their work. This leads to frequent mutations in the viral genome; these are normal and expected.

“Importantly, the vast majority of these mutations either “break” the virus such that it can’t transmit and/or replicate anymore, or don’t change the virus at all because of redundant encoding. This means that the mutations don’t change the proteins, and therefore function, of the virus in any way. Other changes may modify a protein of the virus very slightly, but not impact the function at all. Rarely, a change in the genetic code of a virus can help it to replicate and/or transmit better, but nearly all of these changes still have only a tiny effect.


“Rarely, a change in the genetic code of a virus can help it to replicate and/or transmit better, but nearly all of these changes still have only a tiny effect.”


“Variation in viruses’ genetic code is useful for tracing outbreaks

“These differences in the genomes between viruses can be used as “bread crumbs” to trace the history of a given sample.  Just as the people in your family share unique combinations of genetic characteristics, closely related viral samples share unique combinations of genetic mutations.

“For example, here we show the viral “family tree” with each sample colored by which amino acid is present at a specific location in the viral genome (gene “ORF3a”, site 57).

“Highlighting samples from New York, we see that most of the cases from New York and Europe have the amino acid Histidine (“H”) rather than Glutamine (“Q”) at this position. This, in combination with all the other sites in the genome, tells us that these cases are all closely related to each other.

“The evolutionary rate of SARS-CoV-2 is typical for a coronavirus

“Because viral genomes inevitably change, these differences tend to accumulate at a steady rate over time…”

“While there are certainly some outliers, on average, we see changes accumulate at a rate of ~24 substitutions per year.  This means that if a single viral lineage were transmitting from one person to the next for a full year, we’d expect its entire genome to accumulate roughly 24 substitutions by the end of the year. As the whole SARS-CoV-2 genome is ~30,000 bases, this corresponds to roughly ~1 mutation per 1,000 bases in a year.

“For context, influenza would average ~2 mutations per 1,000 bases per year; HIV would average ~4 mutations per 1,000 bases per year.

“As far as we know, there is only 1 strain of SARS-CoV-2

“There have been many reports about multiple “strains” of SARS-CoV-2.  First, a clarification: when virologists use the word “strain,” it’s often just as a useful label so we can all refer to the same group of samples (e.g., our clade labels, shown here). This does not imply any known functional difference.

“Separately, “strain” can be used to refer to viral genotypes that are functionally distinct, either biologically (e.g., pathogenicity/disease severity) and/or epidemiologically (e.g., transmissibility). Importantly, though, determining whether two genotypes actually are functionally distinct requires much more experimental, clinical and epidemiological data than we currently have.

“One of the most prominent hypotheses about SARS-CoV-2 strains compares possible “D614” vs “G614” strains.

“D614G may be related to transmissibility, but could also be explained by geography
A recent pre-print suggests that a single mutation, D614G (from amino acid “D” to “G” at site 614 in the “S” (‘spike’) protein), may be responsible for increasing the transmissibility of SARS-CoV-2.


“D614G may be related to transmissibility, but could also be explained by geography.  A recent pre-print suggests that a single mutation, D614G (from amino acid “D” to “G” at site 614 in the “S” (‘spike’) protein), may be responsible for increasing the transmissibility of SARS-CoV-2.


“In many geographic areas, the relative frequency of 614G compared to 614D increased over time. If a certain genotype leads to better transmissibility, we would expect it’s frequency to increase over time. There are, however, other explanations to why the relative frequency of some genotypes would increase over time.

“For this site, we see a number of geographic locations where initially, most viral lineages in circulation had the D allele; later, this balance flips such that most lineages have the G allele. This could be a hallmark of G being slightly “fitter” than D (e.g., if viruses with the G mutation had a slightly higher R0 through increased transmissibility).

“However, this could also just be a side effect of the natural history of the pandemic. Early on in the pandemic, most strains exported from China had a D allele. Later, most strains from Italy had a G allele. Recently, we’ve seen more exportation from Europe than from Asia overall (although there’s certainly some sampling bias at play here, as well). Thus, it could just be that this particular genotype got lucky, and spread so rapidly because it got there first.  There’s a fair amount of debate regarding the relative merits of these two hypotheses. It’ll be important to carefully tease these apart, but we don’t have scientific consensus on this issue yet. For a more detailed explanation, see this thread.


“There’s a fair amount of debate regarding the relative merits of these two hypotheses. It’ll be important to carefully tease these apart, but we don’t have scientific consensus on this issue yet. For a more detailed explanation, see this thread.”


 

“What you can do

“…as an individual

* Practice strict social distancing, especially if you are in a vulnerable group.
* Remember that even if you are not super vulnerable, many people around you are; follow these practices to protect others.
* Wash your hands “like you just chopped a jalapeno and have to change a contact lens.”
* Stay home as much as possible — especially if you are sick; be prepared with extra supplies in case you need to self-quarantine.
* If you are an employer, encourage your employees to work from home wherever possible.

“…as an official

* Make testing free and broadly available.
* Put strong social distancing measures in place.
* Fund and implement extensive contact tracing efforts.
* Financially support those impacted by social distancing measures.

Takeaways

Viruses naturally acquire mutations as they replicate. This is normal. Mutations can also help us trace the course of epidemics.
SARS-CoV-2 mutation rate is very typical for coronaviruses.
As far as we know, there is only 1 functional “strain” of SARS-CoV-2.
Teasing apart the biological impact of specific mutations is tricky — many perceived differences can be attributed to chance and epidemiological factors…”


We provide this link to the article in Nexstrain.org  , but do not try to make the whole article ours.  It does not belong to us. We only give you a flavour of it, so you can make up your own mind if you like and want to support the award-winning journalism behind it, like we do. Of course, we do not or could support all the points made in any article we highlight, but that is part of living in democracy.  We believe the material is relevant to all and is necessary for their personal judgments.


 

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