Ultra-accurate sequencing unveils early somatic lineage selection in Drosophila melanogaster
Authors: Jakob McBroome; Evan Pepper; Cade Mirachandi; Russell Corbett-Detig
Affiliation: University of California, Santa Cruz
Keywords: Comparative genomics & genome evolution
Multicellular organisms are often thought to be genetically homogenous, but their constitutive cells acquire distinct mutations during growth and development. Variation among somatic lineages allows natural selection to act within the body, influencing the genetic composition of the maturing organism. This composition, known as somatic mosaicism, in turn has a significant potential impact on phenotype. Despite its importance, the nature and strength of selection on somatic lineages throughout development is largely unknown. To address this question, we present an ultra-accurate sequencing technique and accompanying analytical pipeline to identify low-frequency mutations within a single tissue sample. We applied this technique to whole Drosophila melanogaster individuals and developed a statistical framework to evaluate the distribution of low-frequency somatic mutations. From the resulting somatic allele frequency spectrum, we inferred a distribution of somatic fitness effects and discovered evidence that ribosomal genes and other metabolic genes are exceptionally conserved, in line with previous studies on the mechanisms of cell competition. Our results suggest that purifying selection plays a significant role in the fate of early developmental mutations and somatic mosaicism overall in Drosophila melanogaster.