Speaker: Ben Dickins (Nottingham Trent University)
Title: Evolution of Small Genomes under Pressure
Date/time/place: 4 March 2015; 3pm; Hendon Campus, room tba
Mutations are the ultimate source of variation for evolution, but in small genomes in particular many mutations are deleterious. The accumulation of deleterious mutations in a population reduces its mean fitness and, if the mutation rate is sufficiently high, can lead to extinction. If lethal mutagenesis is realizable, it could be deployed as an anti-viral strategy and recent work has addressed this in several RNA viruses (e.g., in poliovirus: Graci et al. 2007, and in norovirus: Arias et al., 2014) following on from classic work in HIV (Loeb et al., 1999). I will describe approaches taken in my laboratory at Nottingham Trent University to understand the influence of elevated mutation rates on viral genomes in a single-stranded DNA model organism, the bacteriophage ΦX174.
The persistence of mutant alleles, whether deleterious or not, is also affected by the severity of population “bottlenecks” in which only a small number of individual genomes give rise to subsequent generations. I will describe recent work with colleagues at Penn State University on human mitochondrial DNA. Using samples from apparently healthy family members we applied next-generation sequencing to estimate both the mutation rate and the bottleneck size. This work improves our understanding of this form of inheritance and of how mitochondrial diseases may be transmitted.
I shall explore the evolutionary consequences of mutation in the context of adaptation to environmental change including various forms of “bet hedging” in response to variable environments.
Arias, A., Thorne, L., Goodfellow, I. (2014). Favipiravir elicits antiviral mutagenesis during virus replication in vivo. eLife, 3, e03679.
Graci, J. D., Harki, D. A., Korneeva, V. S., Edathil, J. P., Too, K., Franco, D., Smidansky, E. D., Paul, A. V., Peterson, B. R., Brown, D. M., Loakes, D., Cameron, C. E. (2007). Lethal mutagenesis of poliovirus mediated by a mutagenic pyrimidine analogue. Journal of virology, 81(20), 11256-11266.
Loeb, L. A., Essigmann, J. M., Kazazi, F., Zhang, J., Rose, K. D., Mullins, J. I. (1999). Lethal mutagenesis of HIV with mutagenic nucleoside analogs. Proceedings of the National Academy of Sciences, 96(4), 1492-1497.
Ben Dickins is Lecturer in Molecular Genetics at Nottingham Trent University. During his PhD at the Babraham Institute, University of Cambridge, he worked on the physiological consequences of genomic imprinting at the Gnas locus in mice. In postdoctoral work at Penn State University, he developed methods for polymorphism detection from next-generation sequencing data, applying these to evolving populations of phage. In subsequent work Ben contributed to the mitochondrial DNA sequencing project described above. His research agenda is driven by the expanding capacity to observe evolutionary changes as they occur in real-time and his methods are broadly within the field of “Experimental Evolution”. This is an exciting time in evolutionary biology since hypotheses, which previously could only be developed analytically or tested indirectly, can now be assessed directly and quantitatively.
Please contact Tom Dickins (t.dickins AT mdx.ac.uk) if coming from outside the university.