High-precision binary trait association on phylogenetic trees

Traditional methods for identifying associations between genomic features and traits, or between pairs of genomic traits, struggle when applied to bacterial genomes. While several microbial genome-wid...

microbiologyresearch.org

Replaying germinal center evolution on a quantified affinity landscape

Antibody affinity maturation results from a somatic evolutionary process that takes place in the germinal center. A “parallel replay” experiment on germinal center B cells reveals the evolutionary for...

cell.com

Influenza hemagglutinin subtypes have different sequence constraints despite sharing extremely similar structures

Hemagglutinins (HA) from different influenza A virus subtypes share as little as ∼40% amino acid identity, yet their protein structure and cell entry function are highly conserved. Here we examine the extent that sequence constraints on HA differ across three subtypes. To do this, we first use pseudovirus deep mutational scanning to measure how all amino-acid mutations to an H7 HA affect its cell entry function. We then compare these new measurements to previously described measurements of how all mutations to H3 and H5 HAs affect cell entry function. We find that ∼50% of HA sites display substantially diverged preferences for different amino acids across the HA subtypes. The sites with the most divergent amino-acid preferences tend to be buried and have biochemically distinct wildtype amino acids in the different HA subtypes. We provide an example of how rewiring the interactions among contacting residues has dramatically shifted which amino acids are tolerated at specific sites. Overall, our results show how proteins with the same structure and function can become subject to very different site-specific evolutionary constraints as their sequences diverge. ### Competing Interest Statement JDB consults for Apriori Bio, Invivyd, Pfizer, GSK, and the Vaccine Company. JDB and BD are inventors on Fred Hutch licensed patents related to the deep mutational scanning of viral proteins. National Institute of Allergy and Infectious Diseases, R01AI165821, 75N93021C00015 U.S. National Science Foundation, DGE-2140004 Howard Hughes Medical Institute, https://ror.org/006w34k90

doi.org

Pleiotropic mutational effects on function and stability constrain the antigenic evolution of influenza hemagglutinin

The evolution of human influenza virus hemagglutinin (HA) involves simultaneous selection to acquire antigenic mutations that escape population immunity while preserving protein function and stability...

biorxiv.org

High-throughput neutralization measurements correlate strongly with evolutionary success of human influenza strains

Human influenza viruses rapidly acquire mutations in their hemagglutinin (HA) protein that erode neutralization by antibodies from prior exposures. Here, we use a sequencing-based assay to measure neu...

biorxiv.org