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Evolution Can Quickly Change Cells’ Deepest Foundations [Murray Lab]

Evolution Can Quickly Change Cells’ Deepest Foundations [Murray Lab]

Fumasoni and Murray show how evolution can quickly and reproducibly change conserved features involved in the maintenance of genomes in response to constitutive problems affecting DNA replication.

Four billion years of evolution have produced the remarkable variety of processes that we observe in living organisms. Behind the enormous diversity of cellular structures and functions that natural selection has produced, the processes that perform the foundations of cellular life have kept a remarkably similar architecture. For example, the principles of  DNA replication, the process of copying the genome before every cell division,  are universally conserved. But when you look closely, the details of DNA replication vary between species: the number and function of factors involved in replication differs dramatically between eukaryotes and eubacteria and shows substantial variability amongst eukaryotes.

Variation in fundamental cell biological processes, such as DNA replication, seems paradoxical: how can these processes be modified without being ruined and killing the organism? What selective forces drive these changes, and how do they shape the molecular machineries to allow mechanistic variation without destroying biological functions?

To answer these questions, we perturbed DNA replication by removing from buddying yeast the CTF4 gene, which encodes an important protein for DNA replication. During 1,000  generations of evolution, cells recovered from the severe DNA replication problems induced by the absence of CTF4. The mutations they acquired changed other aspects of DNA replication, as well as two cellular processes closely linked to it: the linkage between sister chromosomes and a checkpoint that detects and responds to DNA damage.

These findings show that cells can evolve quickly when a conserved cell biological processes is perturbed and how reproducible the evolutionary pathways that repair such damage can be. Analyzing how the DNA replication machinery can change over time is crucial to understand how cell biology has evolved and has implications for short-term evolution in response to selective challenges intimately linked to replication, such as those that arise in cancer and antibiotic resistance.

By Marco Fumasoni and Andrew Murray


Andrew Murray, Murray lab

Andrew Murray (left) and Marco Fumasoni in a recent virtual meeting during the COVID-19 pandemic

Andrew Murray (left) and Marco Fumasoni in a recent virtual meeting during the COVID-19 pandemic