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You Can Thank Fruit Flies for Those Yummy Beers

October 14, 2014

A wonderful side effect of the close relationship between yeast and fruit flies is great tasting beer. Image from Wikimedia Commons

It is as simple as this, beer tastes good.  And if a new study in Cell Reports by Christiaens and coworkers pans out, you can thank fruit flies for some of those delicious flavors.

No, fruit flies aren’t in your beer. Instead, they have forced the evolution of our favorite beast, Saccharomyces cerevisiae, down a path towards making the aromatic compounds that make beer so darned tasty.

See, yeast can’t get around on their own and so they often rely on insects to move to new pastures. In order to have this happen, they need to attract insects. Plants have worked this out by evolving colorful flowers and sweet nectar. And one way that yeast may do this is by generating aromas that fruit flies find irresistible.

The researchers in this study first stumbled onto this possibility around fifteen years ago. Back then the P.I. was a graduate student who left his yeast flasks out on the bench over the weekend.  Over that same weekend fruit flies escaped from a neighboring Drosophila lab and invaded the yeast lab.

In a “you got peanut butter on my chocolate” moment, the yeast researchers found the fruit flies swarming around one set of flasks and ignoring some of the others. A quick look at the flasks showed that fruit flies were ignoring the yeast strains in which the ATF1 gene was knocked out.

The ATF1 gene encodes the alcohol acetyltransferase responsible for making most of a yeast’s fruity acetate esters.  So it makes perfect sense that fruit flies ignored strains deleted for ATF1 because they didn’t smell as good anymore. To confirm this hypothesis, the authors did a fun, controlled experiment.

In this experiment, the authors set up a chamber where they could use cameras to track fruit fly movement.  One corner of the chamber had the smells from a wild type yeast strain and another corner had smells from that same strain deleted for ATF1.  As you can see in the video here, the fruit flies cluster in the corner with the wild type strains.  Fruit flies definitely prefer yeast that can make flowery sorts of acetate esters.

Christiaens and coworkers took this one step further by actually looking at the effect these chemicals had on Drosophila neurons.  They used a strain of fruit fly containing a marker for neuronal response, so that the researchers could “see” how the flies were reacting to wild type and atf1 mutant yeast smells.  As expected from the previous experiments, the olfactory sensory neurons responded differently to each smell.

To confirm that the esters were responsible for this difference, the authors observed the effect of adding esters back to media in which the atf1 mutant yeast were growing. They found that as more esters were added, the activity pattern of the Drosophila neurons shifted towards that seen with the wild type yeast.

OK, so fruit flies like good smelling yeast.  The next question the researchers asked was whether this had any effect on the dispersal of the yeast – and it definitely did.

To test this, they labeled wild type and atf1 mutant yeast with two different fluorescent markers, so the strains could be distinguished from each other. They then spotted each strain opposite from one another on a specially designed yeast plate and let a fruit fly roam the plate. They then removed the fly and the original spots of the yeast cells.

After letting the plate incubate for 48 hours, so that any yeast cells that had been moved around on the plate could grow up into colonies, they washed the plate to remove the cells that had been dispersed by the fly and used flow cytometry to determine the amount of each strain. They found that wild type yeast were transported about four times more often than the aft1 mutant yeast.

These results show that fruit flies are more likely to disperse yeast if the yeast are producing fruity smells.  Given the close relationship between fruit flies and yeast, and the fact that insect vectors are very important for yeast out in the wild, it is reasonable to think that yeast may smell good in order to attract fruit flies to carry them to new places.

This research also again points to the importance of expanding studies to include more than one organism (see our last blog here). By increasing the diversity of organisms in an experiment, we can learn much more about how things work in the real world. And maybe even learn why yeast evolved to give us such delicious beer.

by D. Barry Starr, Ph.D., Director of Outreach Activities, Stanford Genetics

New and improved Locus Summary pages

October 13, 2014

We are pleased to announce that the redesign of our gene-specific pages, which has been ongoing over the past year, is now complete with the release of the reworked Locus Summary page. The page contains all of the information on the previous Locus Summary page, and has a more modern look and feel. Note that the order and organization of the sections has changed, and the order of the tabs across the top of the page has changed as well. New elements on the page include a navigation bar on the left to take you to the different sections of the page, a redesigned map showing genomic context in the sequence section, and a new interactive histogram summarizing expression data. Biochemical pathway information now appears in its own section (see an example), and we have added a History section to replace the previous Locus History tab. If there are no data of a particular type (for example, Pathways), then that section is absent from the page.

Please explore this new page and send us your feedback.

Yeast Gets By With a Little Help From its Friends

October 9, 2014

If you spend any time looking at social media, you’ve seen the viral videos about interspecies “friendships” – heartwarming scenes of elephants playing with dogs, or lions cuddling with antelopes. These animal relationships strike a chord with most people. Maybe they make us feel there’s hope for harmony within the human species, if such different creatures can get along with each other.

Yeast and bacteria may not be this cute, but they too can enjoy a mutually beneficial friendship.

It may not give you quite as warm and fuzzy a feeling, but in a recent Cell paper, Jarosz and colleagues have shown that yeast and bacteria enjoy a friendship too.  However, these microbes have taken it a step further than the larger animals.

Not only do the yeast and bacteria get something good out of the relationship, but the yeast also get a permanent change that they can pass down to their daughters. It is as if being friends with an elephant could give a dog (and her puppies!) the ability to survive on grasses and fruit.

Like koalas with their eucalyptus leaves and pandas with their bamboo, yeast is a nutritional specialist. It is very good at consuming glucose, and will eat nothing else if glucose is available. All the genes necessary to metabolize other carbon sources are tightly turned off in the presence of glucose, a phenomenon termed glucose repression.

As Jarosz and coworkers studied this glucose repression, they stumbled upon the finding that contaminating bacteria could short circuit this process in yeast.  In other words, when yeast and these bacteria grew together, the yeast gained the ability to metabolize other carbon sources in the presence of glucose!  And even more surprisingly, that trait was passed on to the yeast’s future generations.

Here’s how this discovery unfolded.  The authors had plated yeast on medium containing glycerol as a carbon source, plus a small amount of glucosamine, which is a nonmetabolizable glucose analog. Wild-type cells cannot grow on this medium because the presence of the glucose analog makes it seem like glucose is present, causing glucose repression and preventing utilization of the glycerol.

However, there happened to be a contaminating bacterial colony on one plate, and the yeast cells immediately around this colony were able to grow on the glycerol + glucosamine medium.  When those yeast cells were re-streaked onto a fresh glycerol + glucosamine plate, with no bacteria present, they were still able to grow: they had undergone a heritable change. The ability to utilize glycerol in the presence of glucosamine was stably inherited for many generations, even without any selective pressure.

Although the first observation was serendipitous, this proved not to be an isolated phenomenon. The researchers were able not only to reconfirm it, but also to show that it could happen in 15 diverse S. cerevisiae strains. They identified the original bacterial contaminant as Staphylococcus hominis, but showed that some other bacterial species could also give yeast the ability to bypass glucose repression.

This group had previously found a way that yeast could become a nutritional generalist: by acquiring the [GAR+] prion. Prions are proteins that take on an altered conformation and can be inherited from generation to generation.  They usually confer certain phenotypes; one of the best known is bovine spongiform encephalopathy, or mad cow disease.

Luckily for the yeast, the [GAR+] prion is not nearly so devastating. Instead of a deteriorating brain, S. cerevisiae cells carrying the [GAR+] prion can grow on multiple carbon sources even in the presence of glucose.

Since this phenotype was suspiciously similar to that of the yeast that had been exposed to bacteria, Jarosz and colleagues tested them for the presence of the [GAR+] prion, and found by several different criteria that the cells had indeed acquired it. They looked to see if the yeast got other prions as well, but found that bacterial contact specifically induced only the [GAR+] prion.

The next step was to find out how the bacteria were communicating with the yeast.  Since active extracts could be boiled, frozen and thawed, digested with RNAse, DNAse, or proteases, or filtered through a 3 kDa filter without losing activity, the signaling molecule(s) was probably small.  But the researchers ended up with a complex mixture of small molecules, and more work will be needed to find which compound(s) are responsible for this effect.

In the case of animal friendships, it’s believable that intelligent animals are getting some emotional reward from their relationships (If you don’t believe it, the story of Tarra the elephant and Bella the dog in the video below may convince you!). We can’t exactly invoke this for microbes, so why would these organisms have evolved to affect each other in this way?  It seems there must be a “reward” of some kind.

The benefit to yeast cells from their bacterial friendship is that when they carry the [GAR+] prion, they can grow much better in mixed carbon sources and have better viability during aging.

Conversely, the bacteria benefit because [GAR+] yeast cells produce less ethanol than do cells without the prion. This makes a better environment for bacteria to grow, since too much ethanol is toxic. Interestingly, although the bacterial species that were the best inducers of [GAR+] are not phylogenetically closely related to each other, several of them share an ecological niche. They are often found in arrested wine fermentations, which are unsuccessful fermentations in which the yeast stop growing and bacteria take over.

So interspecies “friendships” can have more profound effects than just tugging at the heartstrings of viewers.  One example is the cat that acts as the eyes for that blind dog.  Another is this case, where bacteria can do yeast some permanent good and make a more hospitable environment for themselves in the process.

And this study reminds scientists of two important things. First, that the laboratory environment cannot tell us everything about biology. How often do yeast cells in nature grow as a monoculture on pure glucose, anyway?  And second, that sometimes accidental occurrences in the laboratory, in this case “contamination,” can broaden our findings…if we pay attention to them.  Just ask Alexander Fleming!

by Maria Costanzo, Ph.D., Senior Biocurator, SGD

Redesigned Expression pages

October 6, 2014

The Expression pages have been redesigned and now include a clickable histogram depicting conditions and datasets in which the gene of interest is up- or down-regulated. Expression data are derived from records contained in the Gene Expression Omnibus, and datasets are assigned one or more categories to facilitate grouping, filtering and browsing. Short descriptions of the focus of each experiment are also provided. The PCL files generated for each dataset are used to populate the expression analysis tool SPELL. Also included on the pages are network diagrams which display genes that share expression profiles. The Expression pages provide seamless access to the SPELL tool at SGD, as well as external resources such as Cyclebase, GermOnline, YMGV and FuncBase.

Please explore these new pages, accessible via the Expression tab on your favorite Locus Summary page, and send us your feedback.

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