Research

Evolutionary genetics

This general area underlies a good deal of our work -- motivated to a large extent by a wish to understand the mechanistic bases of evolutionary change. But equally, genetics holds so much fascination and there is so much that remains unknown. It is also one awful lot of fun doing genetics with organisms that are experimentally tractable and where it becomes possible to dissect phenotypes that have arisen during the course of real-time evolution (selection) experiments.

The evolution of phenotypic diversity

Natural selection shapes patterns of diversity, but its ability to do this is constrained by the supply of phenotypically useful variants. This interests us a great deal and is a motivating factor behind the many years spent painstakingly dissecting the phenotypic and gentics bases of wrinkly spreader fitness. This work was begun by Sophie Kahn, one of my first D. Phil. students (see Spiers et al 2002 Genetics 161, 33). She did a wonderful -- pioneering -- job, back in the days before we had a genome sequence and where identifying the genomic location of transposons required Southern blotting and cloning pieces of impossibly large genomic DNA using restriction enzymes whose positions were unknown. Things have progress: we now have a genome sequence of the ancestor (one day it will get published) and this has greatly facilitated our genetic analyses. Of course with such a reference sequence it becomes possible to take advantage of some of the latest genome re-sequencing technologies to wonderful effect (see Christian Kost, Jenna Gallie and Frederic Bertels' pages)

Our approach has been phenotype back to genotype: it took many years to find the causal mutations, but once found, we understood why the mutations had the effects that they do. So far we have published only the wspF story (Bantinaki et al 2007 Genetics 176, 441), but we now know that there are three (and only three) simple genetic routes to WS. Genetic characterization has unravelled some emerging 'rules' governing the origins of these mutants. Mike McDonald -- in particular -- has extended this work to study the full spectrum of mutations (and fitness effects) generating WS in both the presence and absence of selection.

All-in-all, this part of our work is entering an exciting stage with understanding of the system beginning to coincide with the assays and tools to answer the kinds of quesitons that motivate us.

Evolution of a genetic switch

In addition to our work on the evolutionary genetics of the Pseudomonas radiation we have a general interest in the evolution of gene regulation that manifests in various projects (see for example the histidine work). More recently, thanks to Dominik Refardt's interest in the evolution of virulence we got to deal with the genetic switch of phage lambda that determines lysogenic vs. lytic growth. This well-studied switch has been shown to be genetically robust (i.e. it keeps working even through peturbed), which leads to questions about the ecological significance of the swtich and the capacity of the switch to respond to selection.

Dominik performed an interesting selection experiment in which he tried to change the sensitivity of the lambda switch. To our surprise -- and contrary to expectation -- it proved relatively easy to select for either more sensitive or less sensitive switches. In fact in some lines we observed not only a change in switch sensitivity, but also a change in the response time of the switch. Some re-sequencing of derived genomes, along with analysis of candidate loci has provided some new insights into the workings of the lambda switch.

This project took a further interesting turn upon looking at variation in switch sensitivity among natural isolates of lambda phage. It turns out that the switch is very different in different isolates suggestion that natural selection in the wild does tune the switch to prevailing ecological conditions.

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