Brewing Beer In the Age of Infertility

Brewing Beer In the Age of Infertility

It’s time to move past yeast’s fertility problems.

Last week, an article by teams at the Manchester Institute of Biotechnology, the Department of Genetics & Genome Biology at the University of Leicester, and the Department of Chemical Engineering and Biotechnology at the University of Cambridge, was submitted to bioRxiv. This submission (which probably will be peer-reviewed soon) deals with the genetics of yeast.

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Over the past couple of weeks, we have spent time describing work related to yeast’s ecology, evolution, and mutagenesis. While all these advances highlight ways by which we can exploit yeast diversity, we should not overlook another critical factor that drives diversity in nature.


Interestingly, the vast majority of brewing strains are hybrids. In other words, they are the result of a hybridization event (sex) between parents. The majority of brew strains are sterile; however, meaning that to understand or improve yeast genetics, biologists cannot resort to the breeding approaches they commonly use for other organisms. To make such crosses possible and allow breeders to combine valuable traits in new brew strains, a collaborative effort, led by Prof Daniela Delneri, sought to overcome the infertility problem. 

How does mating work?

In a nutshell, yeast mating starts when two gametes (reproductive cells), each with an opposite mating-type (MATa and MAT⍺) meet and hybridize. Meiosis produces gametes, and if both mating types are present, will lead to sexual reproduction. Most diploid yeast hybrids are sterile because they carry only one of the mating-type genes, preventing meiosis. The laboratory circumvented this problem with two smart tricks that induce meiosis and mating between two different species.

Figure 1 from Naseeb et al (2021). Inter-species mating approach to create diploid gametes, suited for sexual reproduction.

In an inter-species approach (see image above), the authors constructed two diploid yeast lines by crossing two haploid cell types, each from different species. These two lines now carry two sets of chromosomes with both MATa and MAT⍺. The authors removed the MATa gene from one of the diploid cell line and MAT⍺ from the other, producing two diploid cell lines, each with different mating types to enable meiosis. The authors then crossed these cells to generate tetraploid yeast cells (and inter-species hybrids), which were then allowed to sporulate. The authors also performed an intra-species approach, which I will not discuss here.

The sporulation process resulted in a population of gametes (diploid), each carrying either the MATa or MAT⍺ gene. The presence of both mating-types, ensure that further sexual reproduction (and therefore recombination) takes place.

Recombination is a critical process that can help maintain diversity in populations. Geneticists can track down the gene shuffling that takes and when combined with phenotyping, linked to improved traits or performance.

The authors capitalized on their results by asking whether they could link gene recombination to improved yeast performance. For this, they first assessed progeny (obtained after about 12 cross events) for fitness in acetic acid, high maltose concentrations (Maltose), low temperature (16°C vs 4°C), heat and ethanol.

The authors then linked phenotypic information to recombination profiles, allowing them to identify regions in the inter-species genomes, that confer beneficial traits. By doing so, the authors indeed identified many new loci (Quantitative Trait Loci or QTLs). Some of these loci were shared between strains, whereas others appeared unique to some hybrid strains. Notably, the authors validated their results by removing the candidate genes found with their work and assessing the resulting phenotype.

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Why is this important? 

Firstly, many brew strains are hybrids and sterile. We were therefor only able to look for natural or induced mutants with enhanced profiles. Now that we can produce fertile hybrids, geneticists can cross hybrid strains and use genetics to identify and combine gene versions (alleles) to optimize strains for any measurable trait.

Secondly, the fact that new QTLs were identified not only shows that the approach is working. It also convincingly demonstrates that classical genetic methods (albeit helped by some clever tricks) can unlock the enormous potential that gene recombination holds

Thus, this work opens the way to create novel strains from yeast isolates and species that already have great value or can add to the diverse gene pool that underpins delicious beer making. 

Until next time. 



Edgar, The Beerologist. 

Edgar Huitema is a Scientist, Brewer & Scientific Consultant at Subscribe to my free newsletter to get the latest advances in science. Contact The Beerologist at ExtrAnalytics if you wish to discuss your needs and our research.

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