Point accepted mutation

A sophisticated model of protein evolution was developed by Dayhoff et al. (1978) who measured the frequency with which each amino acid was replaced by every other in sets of closely related sequences. This was converted into a Markov model, which was used to generate the probability of any amino acid being substituted by any other or remaining unchanged after different amounts of evolution. The amount of evolution was measured in PAMs (point accepted mutations), which are mean numbers of substitutions per 100 residues. This is, of course, the same... 

PAM Point Accepted Mutation. The PAM matrix is a frequency table representing substitution rates for closely related proteins at the particular evolutionary distance represented by multiple sequence alignments. 

The neutral mutation rate differs for each nucleotide in a gene and usually serves as a good indicator for the functional importance of encoded amino acid residue. For example, the C-peptide of proinsulin evolves at a rate (0.526PAM/10 years) much more rapid than that of the A- and B-chains of insulin (0.071 PAM(point accepted mutation)/10 years) because the C-peptide appears to promote the protein folding and is removed pro-teolytically after the insulin has folded to its correct conformation. The greater divergent rate of the C-peptide than that of the A and B-chains reflects the fewer constraints on its... 

Fig. (7). Phylogenetic relationship of tomato subtilases. An unrooted phylogenetic tree is shown based on the amino acid sequences deduced from tomato subtilase genes and cDNAs. Numbers indicate PAM distances (accepted point mutations per 100 residues) between sequences. The figure was modified after (8).

Implicit in Darwin s work is chance represented by the randomness of mutations in the genetic patrimony and their necessary filtering by natural selection. However, the novel point of view that astrobiology forces on us is to accept that randomness is built into the fabric of the living process. Yet, contingency, which is represented by the large number of possibilities for evolutionary pathways, is limited by a series of constraints. 

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