Our latest cryptic lineage paper was accepted in PLoS Pathogens. This paper has some nuanced implications about the origins of SARS-CoV-2. 1/ journals.plos.org
journals.plos.org
There haven’t been a ton of changes to the manuscript since I wrote a post on the preprint, so I’ll make this summary brief and focus on the things that changed. 2/ x.com
x.com
Cryptic lineages are anachronistic, evolutionarily advanced SARS-CoV-2 lineages detected from wastewater. We are pretty certain they are all from persistent infections. We developed techniques for finding these lineages and partially reconstruction their genomes. 3/
We identified 18 cryptic lineages from public databases. They were all derived from lineages that stopped circulating long before they were detected as cryptic lineages. 4/
The cryptic lineages were wildly divergent. 5/
There were a lot of mutations that were convergently acquired by multiple cryptic lineages. Some of these were acquired by more than 50% of the cryptic lineages. I still find this degree of convergence simply astounding. 6/
This is the important bit. Many of the convergent changes were actually reversions to the consensus sequence found in enteric bat sarbecoviruses. 7/
This is the bit we added. Most of the convergent reversions we observed were either neutral or deleterious based on the calculation of independent occurrences by Bloom and Neher. @jbloom_lab academic.oup.com 8/
academic.oup.com
The fact that SARS-CoV-2 already had such changes when it began circulating in humans suggests that it had replicated in a non-enteric environment long enough to allow these substitutions to persist and become fixed in the viral genomes that started the COVID-19 pandemic. 9/ Oh, we found lots of examples of insertions in the cryptics. Not that surprising, Coronaviruses like to do that. 10/
Finally, the reality check. We independently acquired wastewater from one of the cryptic lineages that persisted in 2 different sewersheds (The Ohio cryptic). Sequences from both sewersheds acquired the same mutations synchronously, suggesting they were from a single source. 11/