Comparative Behavioural Genomics
The CBG strategy is based upon principles of evolutionary biology and population genetics to identify system bioParts for synthetic systems design built from evolved diverse components that contribute to diversity in the qualitative and quantitative differences that naturally occur in diverse biological populations. Bacterial strains of the same species can be very different; differing in both which genes they possess (the gene complement) as well as in the versions of genes (alleles) that are present. For example while typical strains of E. coli contain between 4,000 and 5,500 genes, only around 2000 genes are present in all strains of E. coli and the genes that are variably present are many and present in diverse combinations. (E. coli as a species actually contains more different genes than humans do.) In addition, the different gene versions can have different biological activities, including differences in the rates at which different enzymes (biological catalysts) work.
Bacterial strains have remarkable abilities to evolve diversity due to many factors, including:
- Large population sizes
- Long periods of independent evolution
- The ability to exchange DNA between strains, so that parts of a genome can be very old and distantly related to that present in other strains – while other parts of the same genome can be recently and closely related to parts of one or multiple other strains.
- Adaptation to a range of similar and different environments providing different selective pressures on evolutionary developments
- Adaptation to communities in which different co-existing strains have complementary specializations
The objective of the CBG approach is to identify the various combinable components that can be used to create a strain that is better than any that naturally occurs in nature for intended applications, and to use this information to design and construct new versions of these species with novel and optimized behaviour.
In CBG experiments diverse strains from the strain collections for synthetic biology are screened for quantitative behaviours of interest. Comparative analysis is then performed based upon our in-house annotations to determine the genes and gene-versions that are strongly associated with the behaviour of interest. This is a very powerful approach and has the ability to provide a new type of information to assist in synthetic systems design: identification of gene versions that indicate higher and lower activity of enzymes and other products associated with target behaviours.
This is important because most microbial bioengineering is based upon using one of three principle approaches that can be described as ‘system construction’:
- Inserting new genes that add a desired function (often from unrelated species)
- Removing (knocking out) genes that compete with the desired function
- Increasing the expression of a gene to increase a desired function (typically on a plasmid, or using one of a small number of controllable promoters in the chromosome)