Talk:Substitution matrix
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193.51.83.104 (talk)16:35, 23 September 2012 (UTC)[reply]
This sentence is wrong :
"This is primarily due to redundancy in the genetic code, which translates similar codons into similar amino acids."
Because :
"Summarizing, it would appear that, with the exception of synonymous codon transitions, the overall consequences arising from minimal base substitutions favor protein structural diversification rather than structural preservation."(Salemme, PNAS, 1977)
"According to the physicochemical theory of the genetic code(1, 2), allocations of codon domains for the 20 amino acids havebeen determined by the advantage of assigning to amino acidsthat are similar in physicochemical properties neighboringcodons that differ from one another only in a single base. Suchassignments would minimize the chemical distances betweendifferent amino acids encoded by neighboring codons and,therefore, offer protection against damage due to mutationalor translational errors involving a single base change." (Wong, PNAS, 1980)
and
"These findings, togetherwith those of Salemme et al. (8), do not support thephysicochemical theory of the genetic code, which considersdistance minimization to be the predominant factor shapingthe evolution of the genetic code."(Wong, PNAS, 1980)
---
There is a serious confusion in this article about the concepts of substitution and mutation. When sequences evolve neutraly, the substitution rate is the same as the mutation rate, when selection intervines, then the substitution rates are altered with respect to the mutation rates. For example, if strong purifying selection is operative, then the substitution rate will be reduced, while under positive diversifying selection, the substitution rates are increased when compared to the mutation rates. When we analyze a sequence alignment, the differences observed among the sequences are the substitutions that became fixed after the action of selection (if any) and stochastic factors (random drift). Because we cannot measure mutation directly from the alignment, we usually try to model the substitutions instead. If a comprenhensive population model is avaible for the system under study, then the substitution matrix can be written as a function of selection, effective population size, and the true mutation rates. Then we can use the observed substitutions in the alignment to estimate the substitution rate parameters, and decomposed them into the corresponding population parameters. Generally, it is hard to describe substitution matrices in terms of population genetics models, so most of the time the substitution models implemente are phenomenological, and they tend to be descriptive rather than analytic.
80.47.149.18022:35, 27 April 2007 (UTC)[reply]
A stab by someone who's more a student of the topic than an expert on it =)
Please feel very very free to make any changes you want.
Good point. I've now included a definition of log-odds scores.
Reorganisation of Molecular Evolution
I noticed several overlaps and missing aspects in these molecular evolution articles:
When there are no objections, I will reorganize, partly rewrite and extend these articles in the next few days.I would welcome any advice, especially on other related articles that I am not yet aware of.
My concept looks as follows:
09:13, 5 October 2006 (UTC)
Thank you for your comment. I also prefer comprehensive, longer articles. My concern was that having Markov models and DNA models and protein models all in one article might be too much. But your suggestion sounds reasonable. So I'm looking forward to see your version early next week. Then we can discuss the details.wild8oar07:06, 6 October 2006 (UTC)[reply]
Does anyone know what proteins the original PAM matrix was generated from?Aaadddaaammm03:25, 3 November 2006 (UTC)[reply]
Each amino acid is more or less likely to mutate into various other amino acids. For instance, a hydrophilic residue such as arginine is more likely to be replaced by another hydrophilic residue such as glutamine, than it is to be mutated into a hydrophobic residue such as leucine. (Here, a residue refers to an amino acid stripped of a hydrogen and/or a hydroxyl group and inserted in the polymeric chain of a protein.) This is primarily due to redundancy in the genetic code, which translates similar codons into similar amino acids. Furthermore, mutating an amino acid to a residue with significantly different properties could affect the folding and/or activity of the protein.There is therefore usually strong selective pressure to remove such mutations quickly from a population.
There is a big difference between the probability of a substitution (or a point mutation) occurring -- which depends on chemistry and cannot be prevented by selection, except perhaps very indirectly -- and the substitution being discouraged through differential reproductive success, over a much longer time scale.
Maybe it intended as a parenthetical remark outside the primary line of argument, but it doesn't read that way. So, please reword, cite an expert, or remove.84.227.252.224 (talk)16:52, 16 October 2014 (UTC)[reply]
