Principal Supervisor: Dr Andre Pires da Silva - SLS
Co-supervisor: Alfonso Jaramillo - SLS
PhD project title: Variations in meiosis and their consequences to genetic, cellular and organismal diversity
University of Registration: University of Warwick
Eukaryotic organisms that propagate sexually generate gametes by the process of meiosis. Meiosis not only assures the correct ploidy of subsequent generations, but also promotes genetic diversity by generating new allelic combinations. Environmental effects on this variation provides the basis for natural selection and evolution. Despite advances in uncovering the mechanistic basis of meiotic events in model systems, there is little understanding about why there is so much natural variation in meiosis. Few studies have addressed the consequences of this variation at the cellular and organismal level.
Proteins that control the process of meiosis, for example, are surprisingly divergent in primary sequence even within the same species . The behaviour of chromosomes, which seems so crucial for meiosis, may also vary. In the ‘normal’ meiosis, homologous chromosomes pair and undergo crossing-over in meiosis I, and the sister chromatids separate to different daughter cells in meiosis II. In some organisms, however, sister chromatids already separate in meiosis I .
We have been studying a roundworm that has an atypical meiosis , which ultimately influences the sex ratio in the following generation. In contrast to mammals, which have two sex chromosomes, males of this species of roundworm have a single (i.e., univalent or X) sex chromosome. The first difference from the typical meiosis is that, in contrast to the autosomes, the chromatids of the sex chromosome separate already in the first meiotic division. The second difference is that shortly before the second meiotic division there is a major reorganization of the cytoplasm; mitochondria and other essential sperm components follow the daughter cell with the X chromosome. Consequently, only sperm with the X chromosome are functional. These males then, generate mostly XX progeny when mating with females.
We hypothesize that the X chromosome is being used as signal for the cytoplasmic rearrangement. This project will involve the bioinformatics analysis of sequences in the X chromosome, generation of mutants in which males are XX, and mathematical modelling to uncover potential consequences of males always inheriting the paternal X chromosome.
The implications of this work is not limited to this roundworm. By understanding how the X chromosome or other signal might reorganize the cytoplasm will give also insights into how cellular diversity is generated during development.
- Anderson, J.A., Gilliland, W.D., and Langley, C.H. (2009). Molecular population genetics and evolution of Drosophila meiosis genes. Genetics 181, 177-185.
- Heckmann, S., Schubert, V., and Houben, A. (2014). Holocentric plant meiosis: first sisters, then homologues. Cell Cycle 13, 3623-3624.
- Shakes, D.C., Neva, B.J., Huynh, H., Chaudhuri, J., and Pires-daSilva, A. (2011). Asymmetric spermatocyte division as a mechanism for controlling sex ratios. Nat Commun 2, 157.
BBSRC Strategic Research Priority: Molecules, cells and systems
Techniques that will be undertaken during the project:
- Gene editing tools to generated mutant nematodes (e.g., CRISPR/Cas9)
- Generation of transgenic nematodes (e.g., tagging of specific proteins with fluorescent markers)
- Microscopy (e.g., time lapse videos, confocal microscopy)
- Bioinformatics (e.g., writing scripts in Unix, R and Python)
- Mathematical modelling (R, Python)
Contact: Dr Andre Pires da Silva, University of Warwick