GISAID is the main database and global repository of SARS-CoV-2 genetic sequences, and teams from all over the world provide the data currently it houses 80,000 SARS-CoV-2 sequences (, Aug. 2020, bioRxiv) we had found several dozen cases where the G form was increasing, and only a single exception we made a public website () to enable other people to track the D614G frequency relative to the original Wuhan form in any area in the world based on GISAID data. At the time of our bioRxiv submission (Korber et al. This pattern was consistently repeated at virtually every geo/political level: country, state, county, and city, with only very rare exceptions. In local geographic populations where both the G clade and the original Wuhan form co-circulated, the G form repeatedly showed rapid and significant increases in relative frequency. The Wuhan form of the virus rapidly spread throughout the globe in early 2020. What was the evidence indicating that the D614G mutation is more transmissible than the original form? What is the current evidence? Among the later samples, at least some of these result from recombination, and again, not as de novo mutation (Korber et al. While some of these may have been spontaneous dead-end mutations, early examples may have been ancestral to the G clade lineage. There are a small number of GISAID sequences where the 4 base haplotype is disrupted and not all 4 bases are present. G614 is almost always found linked to the other 3 mutations (>99.99% of the time, Korber et al. The G clade differed from the original Wuhan form by 4 mutations. A phylogenetic tree can be thought of like a family tree, and a shared ancestor like a grandmother who is a shared ancestor of all of her grandchildren. A “clade” is a lineage in a phylogenetic tree with a shared ancestral state. The D614G mutation is being carried along as a part of a clade called the “G clade” by GISAID that is named for this mutation. The vast majority of the time it is being transmitted person to person, and not arising independently as a new mutation. Is the D614G mutation recurring in many individuals, or is it being transmitted from person to person? The Spike protein (S) is a string of 1,273 amino-acids in the original form from Wuhan the 614 th of these amino acids has the chemical symbol “D” (aspartic acid), while in the mutated form, the 614 th amino acid is abbreviated “G” (glycine) so S D614G is short for “having a Spike protein with aspartic acid at position 614 mutated to glycine." 2. D614G refers to an amino acid mutation in this protein that has become increasingly common in SARS-CoV-2 viruses from around the world. Can the word “mutation” be applied to an amino acid change?ĭ614 means the original form the mutant form is referred to as D614G, or just G614.The coronavirus that causes COVID-19 uses its Spike protein to infect human cells.Does the G clade represent a new viral strain?.Can a single amino acid alter the phenotype of a protein?.Can you use frequencies to look for signs of evolutionary positive selection?.Why do you think understanding the biology behind the greater transmissibility of the G form is important?.How do you respond to criticism that the increases in the G clade frequency could have happened by chance alone?.What is the evidence that the G614 virus is not associated with greater disease severity?.What was the evidence indicating that the D614G mutation is more transmissible than the original form? What is the current evidence?.Is the D614G mutation recurring in many individuals, or is it being transmitted from person to person?.The variant in question, D614G, makes a small but effective change in the virus’s ‘Spike’ protein, which the virus uses to enter human cells. In this paper, the Los Alamos team and their colleagues provided evidence that particular SARS-CoV-2 mutation was associated with increased viral transmission and the spread of COVID-19, was more infectious in cell culture, and was associated with higher levels viral genetic material in the upper respiratory tract of infected individuals. This is a synthesis of questions Los Alamos National Laboratory researchers and their colleagues have received both from scientists and from the press regarding the paper “ Tracking Changes in SARS-Cov-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 virus, Korber et al., 2020, Cell 182, 1–16. SARS-CoV-2 mutation: You've got questions, we've got answers
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