Quantitative Genetics of Hybrid Yeasts: overcoming sterility and biotechnological exploitation of diversity

Lead Research Organisation: University of Leicester
Department Name: Genetics


Selection for improved characteristics of crops and animals over the millennia of modern human history has benefited from the ability to breed. Artificial selection for such improvement through selective breeding feeds the world as well as gives us the wide variety of dog breeds, faster race horses, etc. Without the ability to breed there is limited variation on which to base improvements. Many plants, including various crops of great importance such as wheat, originated from the hybridization of two or more closely related species. These initially were sterile and dead ends in terms of evolution but overcame their sterility by duplicating their genomes. Variation could still be limited in these as the fertile derivatives may have occurred only once in history resulting in variation being fixed at that point and accumulated over time via mutations. A lot of effort goes into crop improvement by introgressing chromosomes from parental species of the hybrids to bring in new variation. In animals it is more difficult to overcome sterility and so working animals such as mules can only really be improved by breeding in the horse and donkey parents and hoping for improved characteristics in each new mules created by mating the two parents. This is a hit or miss approach and not very efficient.

In fermentation uses with yeast there are hybrids that are used, the most famous being the lager yeast Saccharomyces carlsbergensis. There are also some used in the wine industry and others are found in nature. These are sterile hybrids which preclude improvement by breeding. In this project we overcome the sterility barrier by duplicating the genomes of several new and existing hybrids, first to determine the genetics of particular characteristics, like why does lager yeast ferment better at cold temperatures, and then to create new diverse hybrids with improved or even new characteristics. We will generate a large number of new hybrids and explore their characteristics, isolating useful strains for use in brewing and wine making as well as industrial production strains. We will also learn about the biology of hybrids and how their two genomes interact. Finally we will answer the question 'Can mules evolve?'

Technical Summary

Yeast hybrids are important in many industrial situations including various fermentations used to produce alcoholic beverages. These and other production strains have been improved upon over the decades by relying on mutations and selection. A much greater potential for improvement would be available if these strains were amenable to genetics and breeding. We will apply several mating/fusion techniques to create tetraploids out of existing hybrids and new hybrids created in the lab from extant species in the group. These will then be assessed for basic phenotypes and new genetically variable hybrids will be generated by putting the tetraploids through meiosis. Rather than being sterile the 4n hybrids will generate 2n diploid hybrids similar to the original sterile hybrid created but with new genetic combinations from the input parental strains of each species going into the hybrid. This will make the progeny amenable to the latest QTL analysis techniques in yeast using next generation sequencing on pools of selected individuals. The result will be first the generation of new hybrids with new characteristics, some will have improvements of desired traits. The analysis of these will provide the determination of why these new hybrids are improved. Finally some will be taken through fermentation processes with all the inherent stresses to determine whether the improved strains are still fit for fermentation purposes. Any useful strains will be protected by safe storage in the national culture collection (NCYC). Ultimately we will produce new hybrids to order for various fermentation and industrial purposes.

Planned Impact

Who will benefit from this research?

The opening up of hybrids to genetic analysis and breeding solves an age old problem and is of great potential benefit to several groups, primarily the fermentation industries producing alcoholic beverages but also to the biotech industries producing flavours and other high value compounds as well as those producing platform chemicals for new compound development, biofuels, bespoke compounds from engineered pathways, new enzymes, etc. Beyond the biotech and fermentation industries the methods could be beneficial to agriculture providing a means to bring in more genetic variation to hybrid crops that already have undergone tetraploidization. This research will also reach public and educational communities, such as agricultural and winery colleges (i.e. Plumpton College, East Sussex, UK), delivering awareness in new cutting-edge technologies, such as next generation sequencing and large-scale quantitative trait analysis, and specifically promoting UK basic science in the yeast physiology and evolution community.

How will they benefit from this research?

Immediate benefits will arise from the generation of new hybrid strains with improved properties, which will come along with the knowledge of the underlying genetics providing the improvement. Some beneficiaries will be able to utilize these immediately while other can use the approach on their production strains for improvement or can take the genetic knowledge to help engineer improvements in their strains.

What will be done to ensure that they have the opportunity to benefit from this research?

In addition to the traditional routes of publication and academic seminars, the results of this project will be communicated to target groups through the communications offices of the Universities of Leicester, Manchester and Nottingham and the BBSRC media office. Various activities of the PI, CoIs and Industrial Partner involve a wide range of industrial contacts including the Industrial Platform of the LACE programme under BSBEC, the Industrial members of the EU Cost Action Network on Bioflavours from Yeast, and attendance at conferences concentrating on applied aspects of yeast fermentation such as the ISSY in October 2014 and the Yeast in Bioeconomy in November 2013 where relevant outputs and methodologies will be disseminated. We will engage college students by publishing scientific articles in the "Biological Science Review" (http://www.bsr.manchester.ac.uk/) and by meeting them face-to-face in the 'Meet the Scientists' days, organized by Nowgen, a centre for genetics in healthcare, in Manchester.

Professional development for staff working on the project

The project will offer opportunities for the PDRAs to acquire additional skill sets. These will include training in quantitative trait analysis and NGS informatics as well as communication skills through scientific conferences and public engagement events. By attending the BBSRC Media courses, the PDRAs will achieve a better understanding on how to communicate science to the public and explain research strategies to policy makers and general communities.
Description We have successfully taken a sterile hybrid from the wine industry and made it fertile - now allowing for genetic analysis and manipulation.

We have generated all the parental species strains to go into our new hybrid production and will concentrate first on brewing related hybrids.
Exploitation Route The techniques will be applicable to hybrid crops in the future.

For the yeast hybrid outcomes there will eventually be improved brewing traits with the potential for bespoke yeast hybrids for specific purposes.
Sectors Agriculture, Food and Drink,Manufacturing, including Industrial Biotechology

URL http://www2.le.ac.uk/colleges/medbiopsych/research/gact/projects
Description Discussions with brewers and wine makers. Impact not yet realised but the potential for it has been disseminated and is recognised.
First Year Of Impact 2015
Sector Agriculture, Food and Drink,Creative Economy,Manufacturing, including Industrial Biotechology
Impact Types Economic

Description FEMS 2015 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Discussion in yeast for biotechnology session with a mixed audience resulting in longer term interactions on developing yeast and hybrids for industrial uses.
Year(s) Of Engagement Activity 2015
Description Keynote at Benelux annual yeast meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Several Universities and Industries attended and interest in future collaborations was expressed.
Year(s) Of Engagement Activity 2018
URL https://www.yeasterday.nl
Description Plenary speaker at ISSY33 in Cork 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact New collaborations starting with potential of future benefit.
Year(s) Of Engagement Activity 2017