Current Research
We have been interested in a variety of projects concerned with how the genome evolves. We have recently focussed on the evolution of DNA sequences which control development, particularly in Drosophila, and on the evolution of mobile repetitive DNA sequences.
Our interests are in the application of evolutionary theory to problems in molecular genetics. Currently, our research can be grouped under two main headings:
Evolution of Developmental Processes.
We are interested in the ways in which the DNA sequences that control development evolve, and in the genetic variation in developmental processes that exists in populations. One approach is to investigate the way in which enhancer sequences evolve. These sequences determine the time- and tissue- specific expression patterns of downstream coding sequences. They function through their possession of binding sites for transcription factors. We are interested in the ways in which these sequences change on the microevolutionary scale and the degree to which selective constraints act on the protein-binding sequences and the sequences that do not bind proteins. The focus of this research is the Drosophila melanogaster species group, members of which are sufficiently close that their DNA sequences can be unambiguously aligned. This allows tests for natural selection which simultaneously examine DNA sequence variation within and between species (e.g. Phinchongsakuldit et al. 2004). In addition, we are investigating the ways in which enhancers might initially arise. The binding sites for transcription factors are of low complexity and could be created by mutation and selection from random DNA sequences. This potentially could allow the reasonably rapid evolution of new binding sites in controlling regions, allowing genes to be brought under the control of new transcription factors (MacArthur and Brookfield 2004).
The interaction between transcription factors and their targets forms the building block of networks of genetic interaction that bring about spatial patterns of gene expression. We are interested in modeling the ways in which interactions between transcription factors and their targets might be expected to evolve (Johnson and Brookfield 2003, Cooper et al., 2008, 2009).
References:
Johnson, L.J. and Brookfield, J.F.Y. (2003) Evolution of spatial expression pattern. Evolution and Development 5: 593-599
Phinchongsakuldit, J., MacArthur, S., and Brookfield, J.F.Y. (2004) Evolution of developmental genes: Molecular microevolution of enhancer sequences at the Ubx locus in Drosophila and its impact on developmental phenotypes. Molecular Biology and Evolution 21: 348-363
MacArthur, S. and Brookfield, J.F.Y. (2004) Expected rates and modes of evolution of enhancer sequences. Molecular Biology and Evolution 21: 1064-1073
Cooper, M.B., Loose, M. and Brookfield, J.F.Y. (2008) Evolutionary modeling of feed-forward loops in gene regulatory networks. Biosystems 91: 231-244
Cooper, M.B., Loose, M. and Brookfield, J.F.Y. (2009) The evolutionary influence of binding site organization on gene regulatory networks. Biosystems 96: 185-193
Mobile DNAs and their evolution
Genome projects reveal that mobile DNA sequences contribute a substantial fraction of the DNAs of higher eukaryotes. We are interested in the factors determining the diversity of such mobile DNA sequences, and their relative abundance in genomes. The vast majority of mobile DNAs appear to act as "selfish DNAs", increasing their abundance through their capacity to over-replicate relative to their hosts (Brookfield 2005a). However, the selfish spread of mobile DNAs is less likely in organisms which are partially or completely asexual, and we are investigating, both experimentally and through simulation, the possibility that the maintenance of mobile DNAs in asexual bacteria results from these sequences capacity to act as mutagens. (Edwards et al. 2002, Edwards and Brookfield 2003, McGraw and Brookfield 2006). We are also interested in the consequences of patterns of transposition for the phylogeny of copies in a transposable element family (Brookfield 2005b, Johnson and Brookfield 2006, Brookfield and Johnson 2006, Styles and Brookfield 2007, 2009).
References:
Edwards, R.J., Sockett, R.E., and Brookfield, J.F.Y. (2002) A simple method for genome-wide screening for advantageous insertions of mobile DNAs in Escherichia coli. Current Biology 12: 863-867
Edwards, R. J. and Brookfield, J.F.Y. (2003) Transiently beneficial insertions could maintain mobile DNA sequences in variable environments. Molecular Biology and Evolution 20: 30-37
Brookfield, J.F.Y. (2005a) Evolutionary forces generating sequence homogeneity and heterogeneity within retrotransposon families. Cytogenetic and Genome Research 110: 383-391
Brookfield, J.F.Y. (2005b) The ecology of the genome- mobile DNA elements and their hosts. Nature Reviews Genetics 6: 128-136.
Johnson, L.J. and Brookfield (2006) A test of the master gene hypothesis for interspersed repetitive DNA sequences. Molecular Biology and Evolution 23: 235-239
Brookfield, J.F.Y. and Johnson, L.J. (2006) The evolution of mobile DNAs-when will transposons create phylogenies that look as if there is a master gene? Genetics 173: 1115-1123
McGraw, J.E. and Brookfield, J.F.Y. (2006) The interaction between mobile DNAs and their hosts in a fluctuating environment. Journal of Theoretical Biology 243: 13-23
Styles, P. and Brookfield, J.F.Y. (2007) Analysis of the features and source gene composition of the AluYg6 subfamily of human retrotransposons. BMC Evolutionary Biology 7: 102
Styles, P. and Brookfield, J.F.Y. (2009) Source gene composition and gene conversion of the AluYh and AluYi lineages of retrotransposons. BMC Evolutionary Biology 9: 102
Hellen, E. H. B. and Brookfield, J.F. (2011) Investigation of the Origin and Spread of a Mammalian Transposable Element Based on Current Sequence Diversity Journal of Molecular Evolution 73: 287-296
Brookfield John F.Y. (2011) Host-parasite relationships in the genome. BMC Biology 9: 67.
Past Research
Dr. Brookfield is interested in the molecular population genetics of Drosophila melanogaster combining techniques from theoretical population genetics with molecular biology. In recent years, he has specialised in the genetics and molecular biology of transposable genetic elements in Drosophila and bacteria. He is also interested in the statistical analyses of hypervariable DNA in ecology and forensic science, and some more general problems in evolutionary biology.