Evolution at the genetic level
Evolution acts upon genetic variation within a population so that over many generations, the individuals within the population become better suited, or fitter, to their environment. The variation across the genome is co-adapted to this environment and this variation occurs in unpredictable combinations at different genetic loci. Man has taken advantage of genetic variation for millennia in breeding agricultural animals and crops, and in the domestication of various animals. Such breeding has generally been blind to the underlying genetics until the recent availability of affordable and efficient whole genome sequencing. Even with the genome sequences being known, predicting the breeding outcome is problematic due to the complex interactions within co-adapted gene networks.
Breeding advantages of saccharomyces cerevisiae
S. cerevisiae can easily be bred with controllable haploid and diploid phases and extensive meiosis, which recombines genetic variation along the chromosomes from any two parents. This generates multiple different genetic combinations in a short generation time. This approach is not possible or scalable for prokaryotic and mammalian systems such as E. coli and CHO. A single diploid baker’s yeast cell can rapidly produce billions of diverse progeny, making it an ideal organism for studying evolution and mapping underlying genotype (full genome) to phenotype (observable functional differences).
Sourcing genetic diversity
Since the early days of yeast genetics and the completion of the first yeast genome sequence in 1996, hundreds of strains have been isolated from different wild niches and domestications. Whole genome sequencing reveals hundreds of thousands of genetic variations between any two strains, all of which have passed the test of evolution and are functional. Breeding diverse yeast strains generates combinations of genetic variation that evolution has never seen before. The analysis of these can reveal which combinations are adapted to their environments and which new combinations may provide better phenotypes/traits, such as in domestic processes like brewing or baking.
Key realities of evolutionary genetics
Decades of research into this area have highlighted three fundamental realities of evolution:
- Even the most similar genotypes of a particular phenotype (similar functionality) vary at multiple genes.
- The more relevant diversity in the parents’ genome, the more ‘ammunition’ there is for the progeny to be optimally adapted to the environmental challenges.
- The genetic adaptation by evolution work involves multiple variants of multiple genes. These patterns of multiple variants are not predictable in terms of which genes are involved and which base variants of these genes are effective in delivering a desired phenotype.
Strain optimisation & evolutionary genetics
Creating the optimum strain for manufacturing a given product in bioprocessing can be viewed as the intensive evolution of the host cell, which is desired to be optimally adapted to the bioprocess environment. Once the means of generating the product within the host cell has been established (e.g. gene sequence in a plasmid cassette), the host cell genome is adjusted to meet the commercial and technical requirements for the project.All existing approaches to strain development involve some form of genetic engineering. This includes synthetic biology, which uses in silico technologies to guide and accelerate this process of rational engineering. Breeding, incorporating vast, nature-tested genetic diversity, provides an innovative alternative to host cell adjustment by generating a large, diverse set of host cells to select from and interrogate.
