How Genetic Grammar Shapes Antibody Evolution

Our B-cells use somatic hypermutation to fine-tune their DNA code to make better antibodies — but not all DNA sites are treated equally. A new study from the Pavri lab at the Research Institute of Molecular Pathology (IMP) shows that somatic hypermutation depends not only on specific DNA motifs targeted for mutation but also on their surrounding sequence and their position within the antibody genes. This “genetic grammar” governs how antibodies evolve to improve immune recognition.

A study led by Bianca Bartl and Ursula Schöberl in the lab of Rushad Pavri at the IMP, along with collaborators at the AC Camargo Cancer Center in São Paulo (Brazil), King’s College London (UK) and the National Centre for Biological Sciences, Bengaluru (India), sheds new light on how genetic grammar influences somatic hypermutation in B-cells. Their findings were published in the EMBO Journal.

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Original publication

Bartl, B., Schoeberl, U.E., Valieris, R. et al. Somatic hypermutation patterns are shaped by both motif position and sequence grammar. EMBO J (2025). DOI: https://doi.org/10.1038/s44318-025-00640-9

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