Beyond Invariable Sites: Using Evolutionary Stasis to Map Multilayered Constraints on the Evolution of Viral and Mammalian Genomes
Sergei L Kosakovsky Pond, Hannah Verdonk, Steven Weaver, Gallean Brown, Danielle Callan, Anton Nekrutenko, Darren P Martin, Barbara Holland · 2026
Read Beyond Invariable Sites: Using Evolutionary Stasis to Map Multilayered Constraints on the Evolution of Viral and Mammalian Genomes by Sergei L Kosakovsky Pond, Hannah Verdonk, Steven Weaver, Gallean Brown, Danielle Callan, Anton Nekrutenko, Darren P Martin, Barbara Holland (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/PMC13427764.txt.
Description
Sergei L Kosakovsky Pond and colleagues present B-STILL, a statistical method for finding genome sites that evolution has kept unchanged because change is harmful, not by chance. Standard tools cannot separate these two explanations at sites that never vary. Their 2026 paper applies the framework to viral and mammalian genomes.
The method models how much opportunity each site had to change, given the genetic code and mutation biases, and compares observed stillness against the gene's background rate. Sites passing the threshold are called evolutionary stasis anchors. In clinical and pathogen datasets, these anchors strongly predicted biological importance and disease relevance. Across the genomes studied, thousands of anchors clustered in known functional domains and in uncharacterised structural motifs. The authors present B-STILL as a scalable way to turn uninformative constant sites into precise markers of constraint.
Catalog record
| CREATOR | Sergei L Kosakovsky Pond, Hannah Verdonk, Steven Weaver, Gallean Brown, Danielle Callan, Anton Nekrutenko, Darren P Martin, Barbara Holland |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 66 KB |
| LICENSE | https://creativecommons.org/licenses/by/4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |