Monday, Jan. 18, 2021

Headline today: “Another new coronavirus variant found across California, including L.A. County.” This variant, L425R, which has three mutations to the spike proteins is not the same as the UK variant, known as B117. Describing the L425R variant as “new” is misleading. According to the Jan. 17 Santa Clara County Public Health Press Release, this L452R variant was known in other countries and states, but now comprises an increasing proportion of the COVID cases in several large outbreaks in Santa Clara county as well as other counties, including Los Angeles.

CDC map shows 40 variant cases found in California (7)

In fact, what’s “new” appears to be the discovery of the variant here in California, not the variant itself. Since genomic sequencing is not being carried out evenly nationwide or even statewide, we don’t know when this variant arrived in California or where it came from or whether it is more contagious, more resistant, or more virulent. Its significance is that its numbers in the local population are increasing and studying it is now a priority, as tweeted yesterday by Charles Chiu, (https://profiles.ucsf.edu/charles.chiu) virologist at UCSF. (I decided to follow Dr. Chiu to help me keep current.)

This is one way “new” variants are found–by sequencing coronavirus genomes in places where an unexpected increase of cases has occurred. The COG-UK consortium (See Pandemic Day 283), which sequences about 10% of the genomes in UK COVID cases, discovered the significance of the B117 variant when cases of COVID in southeastern England started increasing at an increasingly high rate. Like the L425R variant in California, the UK mutation was found in a particular location as a result of genome sequencing. Sequencing is a specialized laboratory activity which is not widespread or evenly spread throughout the world, so where a particular variant started or how widespread it is in other countries is simply not known. Hence the problem with naming a variant after a location (“UK variant” or “South Africa variant” for example) or even labeling it as “new.”

Variants only matter when they exhibit behavior that matters to us. Mutations happen all the time and are not significant in themselves. The coronavirus genome has 29,903 nucleotides in which over 12,000 mutations have been catalogued. (See Pandemic Day 240: Mutant). COG-UK reports that about 4,000 mutations have been identified in the spike protein alone (each site can mutate in multiple ways). So even mutations to the spike protein, which enables the virus to bind to the ACE-2 receptor in humans are not always important. A variant matters when a particular combination (sometimes referred to as a “constellation” or “pattern” or “cluster”) of mutations gives the virus an advantage, enabling it to infect more people. Or to affect people more severely. Or to resist treatments and/or vaccines. That combination can then be repeated throughout a population or even occur independently in more than one place.

Which explains why scientific names are more specific than place names, even though place names are easier for us to understand. The trouble is, as explained in today’s Atlantic article, the newer variants’ names are not fully standardized. Three variants prominent in the news today include:

  • UK: often called B117 or B.1.1.7
  • South Africa: referred to as E484K or B.1.351
  • Brazil: P.1 or 20J/501Y.V3 or descendent of B.1.1.28
Excerpt from SARS-CoV-2 lineages (4)

The “B” names come from a system of nomenclature rules described by Rambaud, et. al., in Nature Microbiology, July 15, 2020 (3). This new system is devised to serve as a consistent ongoing method of categorizing new variants, kind of like the way we classify new species starting with their phylum, class, and genus. “We propose,” the article begins, “that major lineage labels begin with a letter.” They begin simply enough with the letters A and B, the two original lineages from Wuhan, and number the different genomes systematically from there.

Ironically, in tables describing the lineages, they are defined by place names. For example, B.1.1.7 : UK Lineage. So we are referring to the variants geographically after all, only in code. Yet whether the lineage originated in the place it was first identified is uncertain, so we’re going in circles unless we refer to the actual amino acid sequence in the genome, which is virtually unintelligible in spoken communication such as a news report or podcast.

The nomenclature for amino acids is ancient by comparison to variant names. It goes back to the late twentieth century. When you see the format E484K, it refers to a single amino acid mutation, i.e. the one that was E (Glutamic acid) has changed to K (Lysine). The single-letter system was designed by Dr. Margaret Oakley Dayhoff (1925-1983), the founder of bioinformatics, to shorten the code needed for amino acids in computer programming. Her story is fascinating–she earned a doctorate in quantum chemistry at Columbia in 1949 and collaborated with Carl Sagan in the 1960’s using her computer program to “calculate equilibrium concentrations of gases in planetary atmospheres.” I highly recommend the Smithsonian article cited below (6).

Dr. Dayhoff’s one-letter nomenclature for amino acids (5)

Dayhoff’s table for amino acids is comparable to the periodic table of elements–that is, it’s nice to use the first letter of the amino acid when you can, but some amino acids start with the same letter, so Glutamic acid is designated E because G already belongs to Glycine. A newly discovered variant, such as the one in California, is often first referred to by a mutation. In this case: L425R, meaning Leucine (L) changed to Arginine (R).

Will our local variant L425R reported as new in the L. A. Times this morning one day become the “California Variant”? Will it get a B number designation? Only time will tell.

Today’s Notable Headlines

“Another new coronavirus variant found across California, including L.A. County,” L. A. Times. Jan. 18, 2021. https://www.latimes.com/california/story/2021-01-17/covid-19-coronavirus-vaccine-update-pandemic

“COVID-19 Variant First Found in Other Countries and States Now Seen More Frequently in California,” Press Release, Santa Clara County Department of Public Health, Jan. 17, 2021. https://www.sccgov.org/sites/covid19/Pages/press-release-01-17-2021-COVID-19-variant-more-frequent-in-CA.aspx

“A Troubling New Pattern Among the Coronavirus Variants,” The Atlantic, Jan. 18, 2021. https://www.theatlantic.com/health/archive/2021/01/coronavirus-evolving-same-mutations-around-world/617721/

“The Coronavirus Is Evolving Before Our Eyes,” The Atlantic, Jan. 15, 2021. https://www.theatlantic.com/health/archive/2021/01/coronavirus-mutations-variants/617694/

Other Sources:

(1) “Update on new SARS-CoV-2 variant and how COG-UK tracks emerging mutations,” Dec. 14, 2020, COG-UK, https://www.cogconsortium.uk/news_item/update-on-new-sars-cov-2-variant-and-how-cog-uk-tracks-emerging-mutations/

(2) COG-UK Consortium, https://www.cogconsortium.uk/

(3) “A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology,” Nature Microbiology, July 15, 2020. https://www.nature.com/articles/s41564-020-0770-5

(4) “Lineage Descriptions,” https://cov-lineages.org/descriptions.html.

(5) “Dr. Margaret Oakley Dayhoff,” The Biology Project. http://www.biology.arizona.edu/biochemistry/problem_sets/aa/dayhoff.html

(6) “How Margaret Dayhoff Brought Modern Computing to Biology,” Smithsonian Magazine, April 9, 2019. https://www.smithsonianmag.com/science-nature/how-margaret-dayhoff-helped-bring-computing-scientific-research-180971904/

(7) CDC COVID-19 Variant Cases, https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html

Why am I doing this?

The coronavirus pandemic will be indelibly written on our memories just as the Great Depression or the Battle of Britain left their mark on past generations. I intend to journal the pandemic experience from three perspectives: as a retired medical technologist, as a historian (Ph.D., 2014), and an ordinary person living through an estraordinary world crisis.

You are on History’s Edge.

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