[BostonCard]

how does this relate to the previous interest in the D614G mutation?

Here's what they write about it:

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.

As they note, there are a lot of different ways to measure whether a mutation increases transmissability.  But here, they suggest that the effect is similar to the fact that 8% of men living in the former Mongol empire have a Y chromosome descendent from Genghis Khan.  It's not that the chromosome contains genetic material that increases fitness in Central Asians; it is that there was the equivalent of a COVID-19 Genghis Khan who spread the virus (which happened to have the D614G mutation) far and wide (hopefully not by raping and pillaging).

BC

[BostonCard]

how does this relate to the previous interest in the D614G mutation?

Here's what they write about it:

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.

As they note, there are a lot of different ways to measure whether a mutation increases transmissability.  But here, they suggest that the effect is similar to the fact that 8% of men living in the former Mongol empire have a Y chromosome descendent from Genghis Khan.  It's not that the chromosome contains genetic material that increases fitness in Central Asians; it is that there was the equivalent of a COVID-19 Genghis Khan who spread the virus (which happened to have the D614G mutation) far and wide (hopefully not by raping and pillaging).

BC