Notes on “Hearing Silence: non-neutral evolution at synonymous sites in mammals”

September 30, 2008

Hearing Silence: non-neutral evolution at synonymous sites in mammals: J. V. Chamary, Joanna L. Parmley and Laurence D. Hurst.

The Gist:

We know that synonymous codons are under heavy selection pressure in bacteria and other organisms with very large populations. In such large populations, even slightly negative mutations are quickly weeded out.

It isn’t clear that this process occurs in mammals. Mammal species have relatively small populations. A small mutation with only slightly negative effects is more likely to survive through generations. 

Codon bias exists in mammals, but non-selection effects explain much of it. One example: DNA repair mechanisms probably favour G and C over A and T when ambiguities are discovered, resulting in long stretches of GC-rich DNA.

There is some evidence that this explanation isn’t sufficient, however. For example, pseudogenes exhibit less codon bias than genes, and rare codons are more common at sites corresponding to protein turns, loops and kinks. 

Some potential selection-based mechanisms for the codon bias in mammals include translational efficiency (matching tRNA levels in order to produce more protein), mRNA stability (producing mRNA with stable structure), and efficient splicing control (making it “easy” to splice out introns).

If it is the case that codon bias is under heavy selection pressure even in mammals, we cannot use it to estimate mutation rates accurately.

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