Anti-Ageing: Health or Beauty?

Tue, 07 Jul 2015 13:52:48 +0000

a guest blog by Jorge I. Castillo-Quan, written for the 2015 Write About Research Competition. If you had not heard of the term anti-ageing you have not noticed spam emails, television advertising, and articles in magazines. The term anti-ageing has definitely permeated our society. Most scientists struggle to explain to their non-scientist friends what their […]

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13 May 2013

"Why does selection care about codon usage (or what really determines ribosome velocity)"


Laurence Hurst
Date & Time:
Wednesday, 22 May at 5pm
Venue: Medical Sciences AV Hill Lecture Theatre (map)
Host: Jurg Bahler (51602)

Owing to the structure of the genetic code more than one codon can specify the same amino acid.  At first sight natural selection should not care which of the multiple synonymous codons is employed as the translated protein will be the same regardless.  That we see selection on codon usage is thus intruiging.  Understanding why selection cares about codon usage is important for understanding how cells work and, in turn, for understanding how to intelligently engineer transgenes.  I provide evidence that selection cares about codon usage because it minimizes errors: it ensures translation is accurate and, in mammals, it ensures splicing is accurate. It is also commonly assumed that, because common codons match common tRNAs, codon usage must affect ribosomal velocity. Using ribosome protection data I find no evidence that in normal conditions codon usage has any effect on ribosomal velocity.  In retrospect this result makes sense as the original logic was flawed - it considered only tRNA supply, not codon driven tRNA demand.  We expect evolution to drive towards supply:demand equilibrium at which point rare codons specified by rare tRNAs wait as long to be translated as common codons specified by common tRNAs.  More generally, we see little or no evidence for RNA mediated effects on translational velocity (either codon usage or mRNA structure). This leaves the problem of what does actually determine ribosomal velocity.  I show that positively charged amino acids entering into the negatively charged ribosome exit tunnel have a profound effect on ribosome velocity.   This can explain the evolution of the polyA tail.  Methods to improve transgenes are suggested by these results.

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