Indels allows proteins to access phenotypes inaccessible to missense mutations

Summary

Indels can allow proteins to access novel phenotypes that are unachievable with missense mutations (1). An anti-retroviral protein TRIM5$\alpha$ required five missense mutations to neutralize Simian Immunodeficiency Virus, but one amino acid duplication was sufficient to confer the same phenotype.

See also

• Not all sequences with improved activity have plausible evolutionary paths via stepwise introduction of mutations

1.

Tenthorey JL, del Banco S, Ramzan I, Klingenberg H, Liu C, Emerman M, et al. Indels allow antiviral proteins to evolve functional novelty inaccessible by missense mutations. Cell Genomics. 2025;5(6):100818. Available from: https://doi.org/10.1016/j.xgen.2025.100818