Henderson Group: Mapping and Remodeling the Recombination Landscape in Chlamydomonas
Supervisors
Professor Ian Henderson and Professor Alison Smith
Importance of Research
Meiosis is fundamental to the sexual reproduction of eukaryotes and involves the reciprocal exchange of genetic information between homologous chromosomes, termed crossover. Crossovers have a profound effect on patterns of genetic variation and genome evolution and are also a vital tool during breeding and crop improvement.
Crossover patterns along the chromosomes are highly non-random and hotspots and coldspots of recombination exist. Furthermore, crossovers interfere with the formation of adjacent events, which means they are more widely spaced out than expected at random, yet how this communication occurs is unknown. Accumulating data have also shown that both chromatin and DNA sequence play important roles in shaping recombination landscapes, but their interactions are still incompletely understood, particularly in the green algae.
The mechanisms that control recombination number and pattern are thus critically important for understanding genome structure and evolution and are the main focus of this project.
Project Summary
In this project the student will harness the power of Chlamydomonas genetics to generate genome-wide maps of meiotic recombination. They will cross divergent strains of Chlamydomonas and generate tetrads of progeny. Four tetrads are produced from each meiosis and sequencing all members of a tetrad provides a complete, high resolution picture of all recombination events across the chromosomes. New advances in long-read sequencing technology (e.g. Oxford Nanopore) will be used to generate gold-standard maps of the recombination events and the first base pair-resolution maps in a green algae.
Work in the Smith group has identified that metabolism and availability of vitamin B12 have significant effects on transposon mobility, likely via chromatin. As discussed, chromatin is also known to play a major role shaping the recombination landscape in green plants. Therefore, this project will also utilize tools and strains available in the Department to investigate how chromatin, metabolism and the activity of transposons interact to shape the recombination landscape.
What will the successful applicant do?
The student will cross key Chlamydomonas strains and generate populations of tetrad progeny. They will use these tetrads to isolate genomic DNA and generate long-read DNA sequencing libraries for analysis with Nanopore flow cells. They will use the resulting data to identify patterns of recombination and relate this to genetic and epigenetic features of the genome. They will repeat mapping experiments in situations where metabolism, or chromatin, are altered and use this to understand how the recombination landscape is changed
Training Provided
The student will gain experience in molecular genetics using the model green alga Chlamydomonas. They will also gain training in cutting-edge nanopore sequencing; from DNA extraction and library construction, through to bioinformatics analysis and genome assembly approaches. They will also learn how to analyse chromatin, DNA methylation and metabolism and integrate this understanding with their recombination maps. Overall, an advanced training in genetics, genomics and computational biology will be provided to the student, with relevance to algal biology and biotechnology.
References
Lambing, C., Kuo, P.C., Tock, A.J., Topp, S.D. and Henderson, I.R. ‘ASY1 acts a gene dose-dependent antagonist of telomere-led recombination and mediates crossover interference in Arabidopsis’ (2020) PNAS 117: 13647-13658.
Helliwell KE, Collins S, Kazamia E, Purton SP, Wheeler GL and Smith AG (2015) Fundamental shift in vitamin B12 eco-physiology of a model alga demonstrated by experimental evolution. ISME J, 9: 1446-1455.
Choi, K., Zhao, X., Kelly, K.A., Venn, O., Higgins, J., Yelina, N., Hardcastle, T., Ziolkowski, P., Copenhaver, G.P., Franklin, C. McVean, G.A. and Henderson, I.R. ‘Meiotic crossover hotspots overlap with H2A.Z nucleosomes at Arabidopsis gene promoters.’ (2013) Nature Genetics 45: 1327-1336.