The evolutionary plasticity of chromosome metabolism allows adaptation to constitutive DNA replication stress.

Marco Fumasoni,Andrew W Murray

doi:10.7554/elife.51963

Abstract

Many biological features are conserved and thus considered to be resistant to evolutionary change. While rapid genetic adaptation following the removal of conserved genes has been observed, we often lack a mechanistic understanding of how adaptation happens. We used the budding yeast, Saccharomyces cerevisiae, to investigate the evolutionary plasticity of chromosome metabolism, a network of evolutionary conserved modules. We experimentally evolved cells constitutively experiencing DNA replication stress caused by the absence of Ctf4, a protein that coordinates the enzymatic activities at replication forks. Parallel populations adapted to replication stress, over 1000 generations, by acquiring multiple, concerted mutations. These mutations altered conserved features of two chromosome metabolism modules, DNA replication and sister chromatid cohesion, and inactivated a third, the DNA damage checkpoint. The selected mutations define a functionally reproducible evolutionary trajectory. We suggest that the evolutionary plasticity of chromosome metabolism has implications for genome evolution in natural populations and cancer.

Highlights

The central features of many fundamental biological processes have been conserved since the last common ancestor of all extant organisms
Ctf4 is a homo-trimer, that serves as a structural hub within the replisome and coordinates different aspects of DNA replication by binding the replicative helicase, the primase, and other factors recruited to the replication fork (Figure 1A; Gambus et al, 2009; Samora et al, 2016; Simon et al, 2014; Tanaka et al, 2009; Yuan et al, 2019)
Ctf4 is essential for viability in vertebrates (Abe et al, 2018; Yoshizawa-Sugata and Masai, 2009), insects (Gosnell and Christensen, 2011), and some fungi (Harris and Hamer, 1995; Williams and McIntosh, 2002) but cannot be detected in prokaryotes, where there is a direct physical linkage between the primase (DnaG) and the helicase (DnaB) (Lu et al, 1996)

Summary

Introduction

The central features of many fundamental biological processes have been conserved since the last common ancestor of all extant organisms. Many of the proteins involved in these processes are essential, and the complex molecular interactions between them have been argued to constrain the evolution of both the processes and the proteins that carry them out (Hirsh and Fraser, 2001; Jordan et al, 2002; Wilson et al, 1977). The strength of these constraints has been questioned by studies that demonstrated that organisms can evolutionary adapt to the removal of important, and sometimes essential cellular genes (Liu et al, 2015; Rancati et al, 2008). A common feature of replication is the organization of these enzymatic activities in multi-molecular complexes called replisomes, whose function is to coordinate the simultaneous synthesis of DNA from the two anti-parallel template strands (Yao and O’Donnell, 2016)

Methods

Results

Conclusion