Cell-lineage selection interacts with development and life history to shape the rates and identity of heritable mutations

In Drosophila melanogaster, cell-lineage selection biases transmission of a mutation affecting cellular proliferation, and the bias shifts across the individual’s reproductive lifespan.

• Why it matters: Mutation rates are typically modeled as molecular properties, but this work tests whether within-organism selection among cell lineages reshapes both the rate and identity of heritable mutations.
• What they did: The authors combine mathematical modeling with experiments in Drosophila melanogaster, treating mutation rates as emergent from molecular mutagenesis, development, life history, and cell-lineage selection; they also extend the model genome-wide.
• The result: The model predicts modest cellular fitness effects can substantially change transmission probability, and genome-wide analysis shows developmental parameters and the cellular distribution of fitness effects alter estimated mutation rate and transmitted-mutation composition.

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