Use this URL to cite or link to this record in EThOS:
Title: The evolution of functional non-coding DNA in humans
Author: Bird, C. P.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2010
Availability of Full Text:
Full text unavailable from EThOS.
Please contact the current institution’s library for further details.
By studying the patterns of nucleotide variation in conserved non-coding (CNC) sequences in comparison to coding and non-coding regions of the genome, I demonstrated that not only coding sequence but also CNC sequences have been under active selective constraint in humans. I identified a subset of CNC sequences with a significantly accelerated nucleotide substitution rate in the human lineage (relative to chimpanzee) by comparing whole genome alignments of human, chimpanzee and macaque. SNPs within these ‘accelerated CNCs’ (or ANCs) have a significant excess of high frequency derived alleles and high FST values relative to control CNC sequences, indicating that accelerated sequence evolution and positive selection is recent in human populations. ANC sequences are also enriched within the most recent segmental duplications, suggesting recent changes in selective constraint following duplication. A substantial number of SNPs within ANC sequences (34%) are associated with changes in gene expression phenotypes. This analysis suggests ANC sequences have played, and still play, a role in human evolution – potentially through changes in gene regulation. I designed and validated a paralog-specific gene expression array to array the expression of recent human paralogs in diverse human tissues. I then analysed this novel dataset to investigate the influence of the mode of duplication on the patterns of differential expression, and attempted to reconcile the observed patterns with those of the predicted models of paralog fates.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available