University of Cambridge > Talks.cam > Seminars on Quantitative Biology @ CRUK Cambridge Institute  > Accelerated substitution rates in non-coding sequence: Gene duplication, transcription factor binding site turnover and biased gene conversion.

Accelerated substitution rates in non-coding sequence: Gene duplication, transcription factor binding site turnover and biased gene conversion.

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Differences in the gene regulatory network are hypothesized to contribute significantly to phenotypic divergence between and within species. Non-coding sequences with bursts of lineage-specific changes are promising candidates, because clusters of nearby substitutions are a hallmark of selection potentially modify evolutionarily conserved regulatory elements. Performing a comprehensive, genome-wide analysis, we find that genomic loci with high substitution rates in the human-chimp lineage are over-represented near genes that duplicated in the human-chimp ancestor. We also developed a method to screen for nucleotide substitutions predicted to affect transcription factor binding. Rates of binding site divergence are elevated in non-coding sequences near duplicated loci with accelerated substitution rates. Finally, GC-biased gene conversion (gBGC) is a non-adaptive, recombination-associated explanation for accelerated substitution rates. Explicitly modeling this effect we re-analyze loci with the most pronounced human specific acceleration in substitution rate (HARs) and find that the majority (~80%) is unlikely to be driven by gBGC alone.

This talk is part of the Seminars on Quantitative Biology @ CRUK Cambridge Institute series.

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