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Title: Gene expression dynamics underlying diversification and expansion of an actin gene family
Author: Tunnacliffe, Edward Alan John
ISNI:       0000 0004 7229 305X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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During the evolution of gene families, functional diversification of proteins often follows gene duplication. However, some gene families expand while preserving protein sequence. Why would a cell need to maintain multiple copies of the same gene? In this thesis I have addressed this question for an actin gene family containing 17 genes encoding an identical protein in the social amoeba Dictyostelium discoideum. Using bioinformatics I identified several highly conserved sequence elements as potential regulatory motifs, yet found that gene expression patterns during development are broadly similar across the gene family. Turning to live cell imaging I showed that family members display different transcription dynamics, with strong 'bursty' behaviours contrasted by more steady, continuous transcriptional activity. By switching promoters I showed that different dynamics are directly determined by endogenous promoter sequences, rather than genomic context. I have explored how cell-to-cell variability in gene expression introduced by bursty transcription propagates to resultant cytoplasmic mRNA and protein and showed that population variance of these molecules is reduced compared to nascent transcription. Finally, I generated cell lines with up to 6 genes knocked out and showed that these cells potentially display a minor defect in growth. Overall these data suggest that expanded gene families are utilised not only to generate sufficient protein for normal cell physiology, but also to enable both robustness and responsiveness to a range of stimuli regulating the expression of essential genes.
Supervisor: Chubb, J. R. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available