Yeasts lose DNA-repair genes, and thrive

Researchers have discovered a genus of yeast that has lost many of the genes that help other organisms stay cancer-free.

Most organisms have a variety of genes that repair mutated DNA and help keep cell division in line, slowing the overall rate of mutation. However, scientists led by Jacob Steenwyk from Vanderbilt University in Tennessee, US, have found that members of the Hanseniaspora genus, some of which are commonly found in grapes and grape must, have lost large numbers of these genes without apparent consequence.

“Because of their importance in ensuring genomic integrity, most genome-maintenance-associated processes are thought to be evolutionarily ancient and broadly conserved,” explain the authors of the study, published in the journal PLOS Biology. 

“Deletion of many of the genes associated with DNA maintenance leads to dramatic increases of mutation rates and gross genome instability.”

The researchers analysed 25 Hanseniaspora species genomes and found two lineages, one of which evolves faster than the other. While both had lost a large number of the genes that help regulate the cell cycle and preserve genome integrity, the faster-evolving line had lost most. 

As a result, the authors write, it went through a “burst of accelerated evolution, which resulted in greater mutational loads”.

“In genomic terms, Hanseniaspora are the yeast with the least,” says Steenwyk. “They have very small genomes and among the smallest numbers of genes of any species in the lineage.” {%recommended 8648%}

Co-author Antonis Rokas says the rate of mutation in these yeasts is unprecedented. 

“Their cell division appears to be extremely fast but also somewhat erratic – a quantity-over-quality approach, so to speak,” he says.

The findings shed light on the extent to which an organism can tolerate the absence of genetic material, according to Wayne Crismani of St Vincent’s Institute of Medical Research, in Melbourne, Australia. 

“These species of yeast have lost a large selection of some of the most fundamentally important types of genes that typically are used to keep the organism’s DNA intact for survival and propagation,” he explains.

Simon Conn from Flinders University, Australia, says loss of even one of these genes can be lethal for yeast, and for humans can be a “hallmark of cancer”.

“Some of the most commonly detected mutations in cancer-causing genes, or oncogenes, belong to the DNA repair pathway and cell cycle checkpoint pathways,” he adds.

Such mutations can cause high numbers of further mutation – that is, an accelerated rate of evolution – and rapid growth in tumours, allowing cancer to survive in the human body and resist chemotherapeutic drugs, Conn explains.

“The similarities between the growth and mutation profiles seen in this yeast, albeit over millions of years, and that of human cancers is striking,” he says.

Conn says the findings may eventually help coordinate new therapies to target DNA repair pathways, while Crismani suggests they could be useful in helping increase the rate of genetic diversity in yeasts for brewing and baking, or even in plant breeding.

However, the key finding from Steenwyk and colleagues is that, counter-intuitively, the genus has not been adversely affected by the loss of protective genes.

“We conclude that Hanseniaspora is an ancient lineage that has diversified and thrived, despite lacking many otherwise highly conserved cell-cycle and genome integrity genes and pathways, and may represent a novel, to our knowledge, system for studying cellular life without them,” they conclude.