Growth-laws and invariants from ribosome biogenesis in lower Eukarya

TL;DR

This paper derives fundamental growth relations and invariants for eukaryotic cells based on ribosome biogenesis, extending bacterial models to yeast and potentially other unicellular eukaryotes, with implications for understanding cell growth and cancer.

Contribution

It introduces the first invariants of eukaryotic growth linked to ribosome biogenesis, derived from first principles, and demonstrates their applicability to yeast and potential relevance to cancer cells.

Findings

Confirmed proportionality between ribosomal proteome fractions and growth rates in yeast.

Derived two growth-laws for RNA polymerases involved in ribosomal RNA synthesis.

Predicted invariants of eukaryotic growth conserved across conditions.

Abstract

Eukarya and Bacteria are the most evolutionarily distant domains of life, which is reflected by differences in their cellular structure and physiology. For example, Eukarya feature membrane-bound organelles such as nuclei and mitochondria, whereas Bacteria have none. The greater complexity of Eukarya renders them difficult to study from both an experimental and theoretical perspective. However, encouraged by a recent experimental result showing that budding yeast (a unicellular eukaryote) obeys the same proportionality between ribosomal proteome fractions and cellular growth rates as Bacteria, we derive a set of relations describing eukaryotic growth from first principles of ribosome biogenesis. We recover the observed ribosomal protein proportionality, and then continue to obtain two growth-laws for the number of RNA polymerases synthesizing ribosomal RNA per ribosome in the cell. These growth-laws, in turn, reveal two invariants of eukaryotic growth, i.e. quantities predicted to be conserved by Eukarya regardless of growth conditions. The invariants, which are the first of their kind for Eukarya, clarify the coordination of transcription and translation kinetics as required by ribosome biogenesis, and link these kinetic parameters to cellular physiology. We demonstrate application of the relations to the yeast S. cerevisiae and find the predictions to be in good agreement with currently available data. We then outline methods to quantitatively deduce several unknown kinetic and physiological parameters. The analysis is not specific to S. cerevisiae and can be extended to other lower (unicellular) Eukarya when data become available. The relations may also have relevance to certain cancer cells which, like bacteria and yeast, exhibit rapid cell proliferation and ribosome biogenesis.