Junk DNA, cell size, and a new model of cell growth

Why do some cells carry vast amounts of non-coding DNA while the fastest-growing cells carry so little? In this talk, I will present a quantitative framework that links non-coding DNA abundance to cell growth and cell size. Using a scalable genome-expansion system in budding yeast, we increased genome size by adding predominantly non-coding human DNA while leaving the native genome unchanged. The added DNA slowed growth, increased cell size, and lowered endogenous mRNA concentration by drawing RNA polymerase II away from native genes, showing that excess non-coding DNA can act as a sink for limiting transcriptional resources. I will then connect this result to our broader model of eukaryotic growth that is based on single-molecule ribosome tracking, spike-in RNA sequencing, and quantitative proteomics across nutrient-limited conditions. These measurements show that cellular growth is controlled primarily by proportional scaling of mRNA and ribosome concentrations, whereas peptide elongation speed remains essentially constant. Together, the two studies support a simple idea: growth depends on maintaining a sufficient mRNA pool to drive protein synthesis, and genome expansion can reduce growth by competing for the transcriptional machinery needed to sustain that pool. This provides a mechanistic link between junk DNA, cell size, and proliferative capacity, and suggests a general constraint on genome evolution.