Researchers in the Basic Sciences Division track evolutionary origins for an essential protein

Unexpected flexibility and evolutionary constraints shape how HIV-1 overcomes a key human antiviral protein.

Abstract. The Genetics Society of America Mentorship Award recognizes members of the scientific community for exceptional mentoring of geneticists at any c

Hidden no longer. By peering beyond sequence similarity, this work reveals that a core centromere chaperone has been conserved across animals far more broadly than we realised.

Fred Hutch Cancer Center scientists have developed an experimental strategy to give genetically engineered CAR T cells help they'd normally find within lymph nodes -- but on the go, within the tumor. The new genetic tweaks rewired CAR T cells to respond...

Bacterial resistance to the vital last-resort antibiotic colistin is an increasing challenge. This study shows that magnesium sequestration by C. albicans enables P. aeruginosa to evolve much higher l...

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

The Polycomb Repressive Complex 2 (PRC2) is an ancient, conserved chromatin-interacting complex that controls gene expression, facilitating differentiation and cellular identity during development. It...

An ancient protein domain insertion seamlessly preserved conformational signaling while providing a novel surface for adaptation.