Evolving moulds

Like many biologists, Ricardo C. Rodríguez de la Vega searches the world for new species. But while other scientists venture into the depths of the ocean or the heart of the jungle, Ricardo and his colleagues visit cheese shops. “Every time we’re traveling internationally for a conference or something, we go specifically to the local cheese shop and say, ‘Give me the wildest blue cheese you have,’” said Ricardo, an evolutionary biologist at the French National Centre for Scientific Research in Paris.

The cheese they buy is alive with fungi; indeed, many cheeses require a particular species of mould to properly ripen. To produce Roquefort blue cheese, for example, cheese makers mix Penicillium roqueforti into fermenting curds. The mould spreads throughout the cheese, giving it not only a distinctive blue colour but also its (acquired) taste. To produce soft cheeses such as Camembert or Brie, on the other hand, cheese makers spray a different species, Penicillium camemberti, on the curds. The fungus spreads its tendrils over the developing cheese, eventually forming the rind. When you chew on a Camembert rind, you’re eating a solid mat of mould. In addition to influencing the taste, mould keeps cheese from spoiling by defending it from contaminating strains of fungi or bacteria.

By comparing the genomes of different species of moulds, Ricardo and his colleagues have reconstructed their history. In the journal Current Biology, the scientists have recently reported that cheese makers unwittingly have thrown their moulds into evolutionary overdrive. They haven’t simply gained genetic mutations to help them grow better in cheese. Over the past few centuries, these moulds also have picked up large chunks of DNA from other species in order to thrive in their new habitat. “It’s such a short time scale in evolution that it’s quite amazing,” said Antoine Branca, an evolutionary biologist at University of Paris-Sud and an author of the study.

Tracing its origins
The first cheese was made thousands of years ago. Cheese makers developed new varieties often by discovering new moulds. It wasn’t until the early 1900s that scientists discovered the identities of the moulds they had been collecting. Only then did it become possible for industrial cheese makers to select certain strains grown in laboratories to produce cheese in factories. Ricardo and his colleagues were curious to see how mould species changed once people began using them to make cheese. After all, wild species of Penicillium mould typically feed on decaying plant matter, not milk.

So the scientists sequenced the genomes of 10 species of Penicillium. Six of them grow on milk — either because they are used to make cheese, or because they can contaminate cheese and spoil it. The other four are never found in cheese, including Penicillium rubens, the mould from which Alexander Fleming discovered the antibiotic penicillin in 1928. The scientists then reconstructed the evolutionary tree of these moulds. At the base was the common ancestor of all 10 species: a wild mould that lived millions of years ago. As its descendants diverged, they gradually adapted to new ways of living.

The scientists could still recognise similarities in these genes, but they also came across large chunks of DNA that looked out of place. These pieces of DNA weren’t present in the closest relatives of each mould species, but they were found in identical form in distantly related species. This kind of swapping is known as horizontal gene transfer.

Sometimes an organism will take up a piece of DNA from another species and incorporate it into its own genome.

Scientists discovered horizontal gene transfer in bacteria 60 years ago and soon realised that it poses a serious threat to public health. After bacteria evolve resistance to antibiotics, for instance, those protective genes can be acquired by other species. They become resistant, too.

More common
For years, scientists found little evidence of horizontal gene transfer among eukaryotes — species such as animals, plants and fungi. But now that scientists are taking a closer look at more genomes, horizontal gene transfer is turning out to be more common than previously thought. Cheese moulds are enthusiastic adopters of foreign DNA, Ricardo and his colleagues found. Up to 5 per cent of the entire genome of each mould they studied was made up of DNA from another species. This DNA has been jumping among species within the past few centuries, the French scientists report — probably as a direct result of cheese making.

The fact that chunks of adopted DNA are identical in different species suggests they were shared recently, in evolutionary terms. The scientists examined the two biggest chunks of DNA transferred between moulds. The biggest, called Wallaby, contains 250 genes. The next biggest, called CheesyTer, contains about 60.

Neither Wallaby nor CheesyTer were present in wild species of mould, and when the scientists compared strains of Penicillium roqueforti, they found the genes only in those used to make cheese. Wallaby and CheesyTer help moulds grow faster on cheese, it turned out: CheesyTer, for example, holds a gene that appears to let moulds break down lactose, a form of sugar found in milk. But the gene also slows the moulds’ growth on a diet of simple sugar.

“We are selecting for things that are not good in the wild, but are good for us,” said Ricardo. The scientists suspect that these chunks of DNA carry other genes beneficial to moulds forced to adapt to life on a cheese curd. Tatiana Giraud, a co-author of the study at the French National Centre for Scientific Research, said that understanding this evolution could give cheese makers new ideas about how to produce new flavours.

But Tatiana also thinks scientists who want to genetically modify moulds to make better cheese should take the lessons of evolution seriously. Other moulds that contaminate cheese might pick up modified genes that help them thrive, becoming even more of a pest
to cheese makers. “You have to be cautious that it might spread to spoilers,” she said.