Single-cell phylogenies reveal changes in the evolutionary rate within cancer and healthy tissues

Abstract

Cell lineages accumulate somatic mutations during organismal development, potentially leading to pathological states. The rate of somatic evolution within a cell population can vary due to multiple factors, including selection, a change in the mutation rate, or differences in the microenvironment. Here, we developed a statistical test called the Poisson Tree (PT) test to detect varying evolutionary rates among cell lineages, leveraging the phylogenetic signal of single-cell DNA sequencing (scDNA-seq) data. We applied the PT test to 24 healthy and cancer samples, rejecting a constant evolutionary rate in 11 out of 15 cancer and five out of nine healthy scDNA-seq datasets. In six cancer datasets, we identified subclonal mutations in known driver genes that could explain the rate accelerations of particular cancer lineages. Our findings demonstrate the efficacy of scDNA-seq for studying somatic evolution and suggest that cell lineages often evolve at different rates within cancer and healthy tissues.