Multiple+coding


 * __NO__**__**TE: THE INFORMATION ON THIS PAGE IS NO LONGER PART OF THE COURSE (removed from main wiki, 2014-2015)**__

Prev: Accuracy and relevance of RNA landscapes Next: Gene regulation networks

TODO List
 * REF: only in eukaryotes are they used for polymerase binding (REF)
 * MOVE THIS EXAMPLE TO "Links to old pages"! Instead, discuss de Boer and Hogeweg (2012) here.

=Multiple coding=

Here we explore another aspect of evolved coding, namely multiple coding. From viruses to mammals, multiple coding of biochemically totally unrelated functions occurs for given molecules. For example in tRNA there are extra contrained regions on 2 helices which are conserved over phylogenies. However only in eukaryotes are they used for polymerase binding (REF). Why? Well perhaps because it makes use of conserved sequence that is there anyway. To study this issue, Hogeweg and Hesper ([|1992]) constructed a model with 2 genes whereby gene A needs a certain target sequence and gene B just needs to bind to gene A. Included as a part of gene A which is more //crucial// for fitness. This crucial stretch can be a different locations on the gene. The evolution of gene B to match gene A was then studied.

Results show that gene B binding to gene A tends to focus on the crucial stretch, i.e. a certain coding evolves which matches to the most conserved (crucial) part of gene A. The crucial part of gene A can therefore be said to code both for the fitness of gene A and for the matching between gene A and B. However, results differ for different mutation rates.

For high mutation rates the binding sequence between genes is as short as possible and small parts on both genes overlap on the crucial part of gene A, i.e. the multiple coding as described above. In effect this causes the selection pressure on the crucial part of gene A to increase and hence lower the //effective// mutation rate. In this way this improves the information holding capacity of the 2 gene system. Multiple coding allows to get above information threshold.With low mutation rates the matching of gene B to gene A occurs on non-crucial and less conserved area. Since non-crucial have a higher mutation rate, mutations in both gene A and gene B help to generate a match between the genes faster. This capacity is selected during evolution.

On the one hand we therefore see that when mutation rates are too high, the system evolves to reduce the impact of mutation and multiple coding both reduces the length of sequence required, and increases the selection pressure on that sequence helping to reduce the effective mutation rate. On the other hand, when mutation rate a very low, the system evolves to take advantage of non-conserved regions (non-crucial) in order to faster generate a match between both genes. The evolved coding therefore appears to develop in such a way as to fairly close to the information threshold (cf mutation rates of different length genomes). Here we see why it happens: **coding adapts to the mutation rates in order to affect the mutation rate!**

So what does this tell us about an evolutionary process?
 * not just selection to get things better
 * also adjusting coding in order to get better: coding length, selection pressure, adjust how to get as high as possible on the Royal Road
 * optimal mutation rate: dependent on sequence length, population size, selection pressure

(NOTE: [|Muller's ratchet] is a consideration of the information threshold when population fitness plays a role in mutations).

Next: Gene regulation networks


 * References**
 * Hogeweg P & Hesper B** (1992) Evolutionary dynamics and the coding structure of sequences: multiple coding as a consequence of crossover and high mutation rates. //Computers Chem. Vol.// 16: 171-182. [|Download PDF]