Amino acid sequence divergence rate

In the 1960, it was noticed that substitutions in some amino acid sequences seemed to occur at a roughly constant rate over time (Zuckerkandl and Pauling, 1965). This is the well known molecular clock hypothesis. For a particular protein such as cytochrome c or myoglobin, it was noticed that there was a linear relationship between divergences of pairs of sequences, as measured by numbers of amino acid differences, and divergences of the species, as measured by dates from the fossil record. There is still considerable debate as to how accurate the molecular clock may be and as to how it might vary systematically depending on the species, type of protein, and kinds of substitutions that are counted. 

Comparison of the amino acid sequences of hemoglobin and myoglobin chains from different species of animals shows that the chains from related species are similar. The number of differences increases with phylogenetically more separated species. On the assumption that proteins evolve at a constant rate, the number of differences between two homologous proteins will be proportional to the time of divergence in evolution of the species. 

With the divergence of two species from a common ancestor, mutations in the structural genes encoding similar proteins result in amino acid differences between the proteins produced by the now separate species. The degree of immunological similarity between any two such proteins is directly related to the evolutionary distance between the two species. Different proteins evolve at different rates. The structural basis for this difference in rate is that, for slowly evolving proteins, changes in amino acid sequence... 

With the determination of amino acid sequences of hemoglobins and cytochrome C from many mammalian sources, sequence comparisons revealed that the number of amino acid divergences between different pair of mammals seemed to be roughly proportional to the time since they had diverged from one another, as inferred from the fossil record (Holsinger, 2004). As a possible explanation, Zuckerkandl and Pauling (1965) propounded a molecular clock hypothesis in which they proposed the presence of a constant rate of amino acid substitution over time. 

In Section VII,B and Fig. 10 we compared the sequences of 13 a-lactalbumins (if the bovine A variant, equine B and C variants, and ovine variant are included), 23 mammalian c-type lysozymes (if donkey, mouse M, bovine stomach 1 and 3, caprine 1 and 2, ovine 1-3, camel 1, deer 2, echidna II, and porcine 1 and 2 are included), and 13 avian c-type lysozymes (if KDIII and PD2 and PD3 are included). Analysis of the sequence differences indicates that, with the recent considerable increase in the number of lysozymes sequenced, there has been an appreciable decrease in the numbers of residues that are invariant in lysozymes as well as for both proteins. Nevertheless, there is still significant overall homology (—35%) between a-lactalbumin and c-type lysozyme. From the similarities in amino acid sequences, three-dimensional structures, intron—exon patterns, etc., there can be little doubt that the concept of divergence is still valid for these proteins. What is controversial are the rate of evolution and the details of the way in which ct-lactalbumin arose, although it is conceded generally that the mechanism involves gene duplication. 

Fig. 13, Approximately linear rates of evolutionary change in the amino acid sequences of three proteins. The time in millions of years (MY) given for each protein is the time required for a 1% change in sequence to occur between two diverging branches of the phylogenetic tree. From reference 126.

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