What Does the Existence of a Hazy Gene Mean?

Omega Yeast’s Research Director, Laura Burns, decodes the implications of the discovery of the HZY1 gene.

What are brewers’ asking about?

Q: Learning about the backcrossing technique you used to find HZY1, could you also use backcrossing to determine the gene that drives low-diacetyl producing strains, or strains that flocculate better? 

A: Interestingly, backcrossing can’t be used effectively when multiple genes are responsible for the phenotype. We got lucky in our research with haze in that respect, because it turned out that the trait was determined by a single gene — and it was dominant, which meant we could segregate and follow the hazy and non-hazy offspring.

Q: What kind of cool resources are out there about CRISPR — to read about the science behind it? 

A: One great one is The Code Breaker. It’s a really cool book that explores CRISPR and gene editing. It focuses centrally on Jennifer Doudna, the biochemist who won the Nobel Prize in Chemistry for her work on CRISPR.

Q: Could identifying the haze gene mean getting rid of things like biofining or other methods used in the cellar to get rid of unwanted haze?

A: This is a popular question. Brewers are picking up on the fact that finding a gene for haze is about getting both great hazy AND non-hazy beer. Both are pretty explicit in the research, since, when identifying a gene and what it does, one of the first things we do is disrupt it, and see if you lose the phenotype (a phenotype just means an observable trait). I’d encourage folks to read the full research paper.

Disrupting the gene in typically non-hazy strains would definitely be another way of limiting the impact of haze in the beer-making process, and may be a way to circumvent some of the issues to make the process more simplified. I’d say it’s certainly hopeful!

Do brewers want haze control as much as they want more hazy options?

Honestly, some brewers don’t mind some haze; even if it’s an IPA that’s more ​‘West Coast’ driven. So, whether the potential for eliminating haze-prone behavior across a variety of strains is an exciting utility kind of depends on who you’re talking to. The couple of people that I’ve mentioned the possibility to, so far, see it even more when combined with our new DKO series — those are our ALDC-producing strains (strains that prevent the formation of diacetyl with intracellular ALDC). Those are both things that streamline the whole process.

Your prior research about dry hop-timing and how it affects haze with ​‘haze positive’ strains comes up with this, too.

Revisiting that with everybody is important. We had the feeling everyone was already aware of it, but there are still some people even this information is new to. We’ve been presenting cool parallel research over the last two years. Part of it was about how we were able to make non-hazy beer using these ​‘haze-positive’ yeast, too. In our experimentation, what we named ​‘haze-positive’ strains were ones that contributed consistently to good, stable, colloidal haze with mid-to-late dry hop timing. Haze positive strains could also present clear with early dry hop timing.

This new research, the genetic study solidifies some of those brew-by-feeling observations into something that’s more scientifically understood; something that’s proven.

Yeast make haze, it’s dry hop-dependent; haze depends on the yeast strain, it depends on the timing of the dry hop, and it even depends on the type of hops, etc. Brewers have experience with seeing that happen now, and get a sense of what’s going on with the yeast and haze by brewing by feeling, versus brewing by what’s actually known and proven. 

You said this new research may actually simplify things a little.

Brewers made these strains through selection via certain brewing processes; it’s that directed evolution that made these strains behave the way they do. And we know haze is variable among strains. So, the principles to manage all of that are pretty complex. This is indeed simpler:

When we disrupt the pathway, exactly what we predict will happen happens. It’s kind of like a mathematical proof, you know. You’ve got the equation in front of you, and it works. And now we can prove it.

So, basically, this more complete understanding might mean we could operate or drive haze more effectively?

Exactly. It’s similar to talking about the ways brewing strains have evolved to get better brewing phenotypes: they ferment maltose, they flocculate well, they are non-phenolic. All of these metrics that we score yeast by. Now, selecting for haze potential is one of the steps to picking the right yeast for the right beer. 

As we continue to talk about this across this year and next, and in our work with brewers every day at Omega Yeast, it will be interesting to keep hearing what brewers think about the applications of this — as in the tools they’re interested in as a result. 

We can certainly see some interesting opportunities for creativity with tools like that. Ultimately, though, it’s up to brewers to use them. 

I keep it open in that way, just like you’re asking, we’re asking brewers, what do you see? What does this inspire or enable in your work? From the response so far, I think the answer is going to be some amazing things.

Has anyone already approached you with an example of how they’d use a strain that has been made hazy, or a hazy strain that’s been made to produce clearer beer? What could you even do with a formerly haze-producing strain that’s not hazy anymore, that you can’t already do?

Well, juice and haze have been used to describe the same style because hazy and juicy have initially been really tied together. But I think what we just showed with this research is you can break that association: you can make juicy beers without haze; you can make hazy beers without juiciness. Now what you’re going to drive in your recipe much more comes down to the tools you use, and the approach to your recipe design.

I have heard people say they’d be interested in trying a non-hazy British V for a juicy West Coast IPA, for example. You could do more ester forward, lower attenuating West Coast styles, if you are looking to do that without having the muddy haze in the picture.

What do you think separating juicy and hazy means for the trajectory of each? Do you think they will both remain as relevant?

Hazy IPAs have developed a practice and an approach to brewing that has definitely made juicy a big feature. People started increasing the hopping rates on the cold side, and haze just came in hand-in-hand with juice like that. They sort of took off together. 

So, juicy and hazy have really sort of meant the same thing in a lot of ways.

But west coast brewers, who weren’t using haze positive yeast, have started to turn some of the practices of a traditional West Coast into more of a juicy West Coast: they’re lowering the IBUs and kettle additions. They’re looking for clean bitterness, but layering in a lot of cold side additions to emphasize fruity, citrus, pine, dank characters of the hops — a heavy focus on the cold side additions to drive more aroma. 

They are not looking for haze, but are adapting a lot of the same approaches and principles into West Coast IPAs.

I think ultimately, this discovery could make a choice between hazy or not hazy easy, kind of like orange juice. Like, do you like it ​‘grovestand’ (extra pulpy) or without the pulp? You decide.
There are probably other more refined analogies but….

You’ve said that there’s so much more to discover about what haze does and is linked to otherwise, too.

Yes, definitely. Another thing we’d love to look into is how haze is said to be making some of the hop compounds more soluble. Some compounds you don’t necessarily want to be soluble. Some of them are bitter, vegetal, green, astringent types of flavors that aren’t the better flavor anyway. With a side-by-side with a hazy or not hazy beer, some of the hazy comes through as bitterness, harshness, green and other characteristics that these hop compounds have. Those are not the ones that people are trying to drive, but they’re also along for the ride. So that’s something that we really need to resolve in some of the sensory that we can do with brewers.

And we still want to understand a little bit more about the driving force behind how brewers domesticated yeast to have haze; meaning, what selective pressure was put on brewing strains to result in the range of haze phenotypes we see? There’s a lot of speculating that we can do with what we know right now — we currently hypothesize that it’s involved with buoyancy and top cropping.

Brewers selected for haze?

Wild strains don’t really have expansions in this gene, and it’s the expansion that seems to be responsible for the haze characteristic, so it seems like we as brewers have selected for the expansion of the gene.

All of the yeast we use in brewing have been highly domesticated: we brewed yeast in wort, which made them evolve to ferment maltose; we selected for yeast from the bottom of the tank, which promoted the ones that were more flocculant. We got rid of phenolics…. 

All of those characteristics within brewing strains exist because of our industrial use of them. Brewers selected for those traits. Haze is another one of those traits that’s been domesticated into yeast, but we just don’t know how it was driven.

One of the hypotheses we have is that Hzy1, a cell surface protein, could affect the hydrophobicity of the yeast. This could allow the yeast to either bind to other yeast cells in suspension and fall out, or potentially get trapped with CO2 and rise to the top of the tank to form the krausen. By top cropping and skimming off the krausen, we’re selecting for those yeasts that have more of that change that makes them more buoyant. That would be our first hypothesis. 

It’s hard to kind of say these things because we could be wrong. It’s conjecture and speculation at this point — a little bit of like, stick-your-head-out-and-say-what-you-think with that. Somebody might criticize that later, but that’s where we’re at at the moment for what deeper questions this research brings up. There’s always more to look into.

Wild strains don’t have haze ability?

Wild saccharomyces strains, to our knowledge, don’t — but non-saccharomyces strains might. In wine, non-saccharomyces strains release a lot of mannoproteins. They end up reducing haze, but the point is that there are other yeast that do things differently.

There isn’t an understanding of why yeasts are expressing these cell surface proteins. A lot of the functions for cell surface proteins are unknown. We don’t know why they’re out on the surface.

HZY1 didn’t have any known function to it. Nobody knew what it did before. Now we have more of the picture.

It’s amazing to think there are still things like this to discover.

It’s kind of funny — with many brewing strains fully sequenced, we know so much, but understanding what genes impact what phenotypes still is not always 100% clear. There are a lot of these genes that people don’t really know what they do.

What you’re talking about here really puts it into perspective that there’s more to yeast than just its application in one thing, like beer.

Yeah, totally. Other industries are so important to understanding more about what yeast are capable of, you know? I mean, you can study strains in the lab all the time, but they’re in one environment, one media. You’re not really putting them through the whole gamut of what they do.

I know a lot of people that can’t wait to get more opportunities to listen in on what this research means. Are you doing any more seminars soon?

The talks that I’ve done so far have been helpful for me, too. You’re just not sure at first if you’re going to be able to engage people with this type of stuff, but I think it’s really interesting for people. I’ve had really focused attention from crowds.

Stay tuned! We’ll let everyone know where to listen in.

Are you getting a sense of what the impact is for brewers already?

Definitely. Here’s a good anecdote about that—

I was talking about how in experimentation, since we can brew two beers that are identical in every way except for haze, we struggle to discern the hazy version’s sensory difference. As a consequence, it’s not looking to us like hazy really equals juicy. It looks like so far, it’s likely they’re not dependent on each other.

This research is touching on some things people already have strong opinions and instincts about. I love that.