Quote:A much discussed mutation in the context of demographic confounding is D614G (nucleotide position 23,403), a non-synonymous change in the SARS-CoV-2 Spike protein. Korber et al. suggested that D614G increases transmissibility but with no measurable effect on patient infection outcome21. Other studies have suggested associations with increased infectivity in vitro18,40 and antigenicity41. Here we conversely find that D614G does not associate with significantly increased viral transmission (median log10(RoHO) = 0, paired t test p = 0.28; Supplementary Data 4), in line with our results for all other tested recurrent mutations. Though clearly, different choices of methodology may lead to different conclusions. A recent study on a sample of 25,000 whole-genome sequences exclusively from the UK used different approaches to investigate D614G. Not all analyses found a conclusive signal for D614G, and effects on transmission, when detected, appeared relatively moderate39.
These apparently contrasting results for D614G should be considered carefully. What is, however, indisputable is that D614G emerged early in the pandemic and is now found at high frequency globally, with 36,347 assemblies in our data set (77.8%) carrying the derived allele (Fig. 1a and Supplementary Data 3). However, D614G is also in linkage disequilibrium (LD) with three other derived mutations (nucleotide positions 241, 3037, and 14,408) that have experienced highly similar expansions, as 98.9% of accessions with D614G also carry these derived alleles (35,954/36,347). It should be noted that the D614G mutation displays only five independent emergences that qualify for inclusion in our analyses (fewer than the other three sites it is associated with). While this limits our power to detect a statistically significant association with transmissibility, the low number of independent emergences suggests to us that the abundance of D614G is more probably a demographic artefact: D614G went up in frequency as the SARS-CoV-2 population expanded, largely due to a founder effect originating from one of the deepest branches in the global phylogeny, rather than being a driver of transmission itself.
Quote:A much discussed mutation in the context of demographic confounding is D614G (nucleotide position 23,403), a non-synonymous change in the SARS-CoV-2 Spike protein. Korber et al. suggested that D614G increases transmissibility but with no measurable effect on patient infection outcome21. Other studies have suggested associations with increased infectivity in vitro18,40 and antigenicity41. Here we conversely find that D614G does not associate with significantly increased viral transmission (median log10(RoHO) = 0, paired t test p = 0.28; Supplementary Data 4), in line with our results for all other tested recurrent mutations. Though clearly, different choices of methodology may lead to different conclusions. A recent study on a sample of 25,000 whole-genome sequences exclusively from the UK used different approaches to investigate D614G. Not all analyses found a conclusive signal for D614G, and effects on transmission, when detected, appeared relatively moderate39.
These apparently contrasting results for D614G should be considered carefully. What is, however, indisputable is that D614G emerged early in the pandemic and is now found at high frequency globally, with 36,347 assemblies in our data set (77.8%) carrying the derived allele (Fig. 1a and Supplementary Data 3). However, D614G is also in linkage disequilibrium (LD) with three other derived mutations (nucleotide positions 241, 3037, and 14,408) that have experienced highly similar expansions, as 98.9% of accessions with D614G also carry these derived alleles (35,954/36,347). It should be noted that the D614G mutation displays only five independent emergences that qualify for inclusion in our analyses (fewer than the other three sites it is associated with). While this limits our power to detect a statistically significant association with transmissibility, the low number of independent emergences suggests to us that the abundance of D614G is more probably a demographic artefact: D614G went up in frequency as the SARS-CoV-2 population expanded, largely due to a founder effect originating from one of the deepest branches in the global phylogeny, rather than being a driver of transmission itself.
(12-20-2020, 11:53 AM)BostonCard Wrote: If I can translate that, they don't think that D614G is more transmissible than other mutations (but also can't prove the negative).
(12-20-2020, 11:53 AM)BostonCard Wrote: If I can translate that, they don't think that D614G is more transmissible than other mutations (but also can't prove the negative).
(12-20-2020, 04:38 PM)M T Wrote: If it wasn't clear from my note earlier, the "new strain" in England is not D614G. (But when D614G was spreading, it was considered the same sort of event.)
(12-20-2020, 04:38 PM)M T Wrote: If it wasn't clear from my note earlier, the "new strain" in England is not D614G. (But when D614G was spreading, it was considered the same sort of event.)
(12-26-2020, 09:52 AM)Griffins78 Wrote: It looks like the variant in the UK is called B.1.1.7. Here’s what William Haseltine, PhD, chair and president of the global health think tank, ACCESS Health International wrote on CNN, “Opinion: Here’s what’s worrying about the coronavirus variant” with a link to this paper, “Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations”Let it simply be said that anything written by William Haseltine should be taken with many grains of salt. He has been characterized as "controversial" by some and in much less flattering ways by others. That doesn't make him wrong, but it does raise questions.
He says, “this new variant tells us important things about the virus: it can adapt to become more easily transmissible and may be able to become more difficult to neutralize and may possibly be able to outsmart the vaccine to a small extent.”
The paper concludes, “We report a rapidly growing lineage in the UK associated with an unexpectedly large number of genetic changes including in the receptor-binding domain and associated with the furin cleavage site. Given (i) the experimentally-predicted and plausible phenotypic consequences of some of these mutations, (ii) their unknown effects when present in combination, and (iii) the high growth rate of B.1.1.7 in the UK, this novel lineage requires urgent laboratory characterisation and enhanced genomic surveillance worldwide.”
(12-26-2020, 09:52 AM)Griffins78 Wrote: It looks like the variant in the UK is called B.1.1.7. Here’s what William Haseltine, PhD, chair and president of the global health think tank, ACCESS Health International wrote on CNN, “Opinion: Here’s what’s worrying about the coronavirus variant” with a link to this paper, “Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations”Let it simply be said that anything written by William Haseltine should be taken with many grains of salt. He has been characterized as "controversial" by some and in much less flattering ways by others. That doesn't make him wrong, but it does raise questions.
He says, “this new variant tells us important things about the virus: it can adapt to become more easily transmissible and may be able to become more difficult to neutralize and may possibly be able to outsmart the vaccine to a small extent.”
The paper concludes, “We report a rapidly growing lineage in the UK associated with an unexpectedly large number of genetic changes including in the receptor-binding domain and associated with the furin cleavage site. Given (i) the experimentally-predicted and plausible phenotypic consequences of some of these mutations, (ii) their unknown effects when present in combination, and (iii) the high growth rate of B.1.1.7 in the UK, this novel lineage requires urgent laboratory characterisation and enhanced genomic surveillance worldwide.”
