New & Noteworthy

Ancient Hybridization Causes Revision of Yeast’s Calendar

August 19, 2015

Just as this monk had trouble pinpointing when Jesus was born, so too did yeast biologists have trouble figuring out when the genome of S. cerevisiae doubled in size. But they had trouble for very different reasons… Image via Wikimedia Commons

Most people assume that Jesus Christ was born around 1 A.D. or 1 B.C. or something like that. After all, that dating system is based on when he was born. 1 A.D. is by definition “the first year of the Lord.”

Now of course no one was actually marking years this way from the get go. In fact, this dating system wasn’t really invented until 525 A.D. by the monk Dionysius Exiguus.

And as can sometimes happen when you look that far back in time, he didn’t quite get the date of Jesus’ birth right. In point of fact, Jesus was most likely born between 4 and 6 B.C.

While not nearly as momentous, yeast biologists may have done something similar with the genome of our friend Saccharomyces cerevisiae. For many years scientists have believed that this yeast underwent a whole genome duplication (WGD) event around 100 million years ago

But if the conclusions reached by Marcet-Houben and Gabaldón in a new PLOS Biology article are correct, then what looks like the WGD event actually happened before there was a S. cerevisiae around to duplicate its genome.

Which would mean that there couldn’t have been a WGD. There is no way for a species to double its genome if it doesn’t yet exist! Instead the authors propose that what looks like a WGD was actually a hybridization of two related yeasts from longer ago than 100 million years.

Once you get past the vocabulary, the idea behind this study is actually pretty easy. Basically, they took pairs of genes that most likely came from a duplication event (ohnologs) and figured out when they diverged away from one another. This is the same idea behind figuring out when chimps and humans shared a common ancestor by comparing homologous genes.

When Marcet-Houben and Gabaldón compared every potential ohnolog in S. cerevisiae, they found that a WGD event could explain the origin of only 15% of these genes. These 15% could be traced back to a time after S. cerevisiae was already around.

The other 85% all looked to have been duplicated before S. cerevisiae yet existed. Which of course means these could not have come from a WGD. A genome that does not yet exist cannot be duplicated. This set of genes must have arisen in a different way.

An origin story that makes more sense than a WGD for these genes is one in which two related species hybridize to form one new species. This kind of thing definitely happens, especially with yeast (and if you like lagers, you can be glad it does!).

Here the idea is that the related species share a subset of their genes from when they had a common ancestor. When these species fuse, the new beast has both sets of genes. A cursory look might suggest that these genes were from a duplication event, especially if there are many large tracts of them. After all, many genes share a lot of homology between species.

It is only with a closer look that you might trace these genes back to a common ancestor that came before the species you are studying even existed. This is, in essence, what Marcet-Houben and Gabaldón found.

From the phylogeny of reference species that they created, the authors were able to get a general idea about which clades these prehybridization species may have come from. The largest peak of duplication from their analysis came from before Saccharomyces split from a clade containing Kluyveromyces, Lachancea, and Eremothecium (KLE). The other major peak came before Saccharomyces separated from a clade that contains Zygosaccharomyces rouxii and Torulaspora delbrueckii (ZT). So the simplest interpretation is that at some point long ago, an ancestor of modern S. cerevisiae was formed from the hybridization of a pre-KLE and a pre-ZT species.

Showing that something like this happened so long ago is fraught with peril. All sorts of things can happen to a genome in more than a hundred million years. And duplicated genes are even trickier because they can mutate at different rates when one copy is gaining a new function. (After all, that is one way that new genes are born.)

So Marcet-Houben and Gabaldón threw everything but the kitchen sink at the genome sequences. They tried at least three different methods for comparing the various sequences, using alternative reference phylogenies and a variety of techniques to show what might happen to their results if genes were mutating at different rates.

With each method they got similar results. Many or even most of the “duplication” events happened before S. cerevisiae was even a species. And on top of all of this they were able to show that they got a similar result when they used a known hybrid, S. pastorianus, and its two founding species, S. cerevisiae and S. eubayanus.

All of this taken together argues that S. cerevisiae did not undergo a WGD in the deep, dark past. Instead, it is the result of two closely related species getting together and creating a new species.

Now this does not necessarily mean there was no WGD in our favorite yeast’s past. There are at least two ways that a hybrid species might have formed, and as you can see in this image from Marcet-Houben and Gabaldón’s article, one of them involves a duplicated genome:

Fig 6. Hybridization scenarios. From Marcet-Houben and Gabaldón (2015), PLOS Biol. 13(8):e1002220.

In the first scenario, shown on the top left, two diploids of different species fuse together to create a yeast with two sets of chromosomes. Eventually, through mutation, translocation, gene loss and whatever other genome sculpting mechanisms are handy, the yeast ends up with double the number of chromosomes of its predecessors.

In the second possibility, shown on the bottom left, two haploids fuse. This fused yeast then undergoes a whole genome duplication and then goes through similar processes as the first model to get to the current genome.

So, although there may have been a WGD, it looks unlikely that it happened to S. cerevisiae. Just as the placement of historic events in our calendar changes when more information is available, the generation of genome sequences for more and more yeast species and new methods for analyzing them are giving us deeper insight into the history of our friend S. cerevisiae.

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

Categories: Research Spotlight

Tags: whole-genome duplication , evolution , Saccharomyces cerevisiae , hybridization