Conceptual phylogenetics questions

Question

[Callahan]

Hello, I am reading a paper and am having a difficult time understanding 2 concepts that they bring up.

What is meant by:

1. “non homogenous rates of substitution between alignment sites”
2. “Heterogeneity in frequency of amino acids across the alignment.”

If someone could help explain these concepts broadly, that would be very helpful! Thanks

Answer 1

[brian.fristensky]

Without seeing the paper there is no context. Presumably, the paper is referring to a multiple alignment of sequences for a protein, taken from many species.

1. Along the length of the multiple protein alignment, the rate of amino acid substitution varies. In some parts of the protein, a high rate of substitution is observed. In other parts, very little substitution is observed across species. Regions with little amino acid substitution are said to be conserved, and conserved regions are typically those which are critical to the function of the protein. The active site of an enzyme, or sites critical to the folding of the protein, are typically conserved. In contrast, the N-terminal regions of most proteins seem to tolerate a large degree of amino acid substitution, and are therefore presumed to be less important to the function.

2. It shouldn't be surprising that the frequencies of the 20 amino acids would vary along the length of a protein, and therefore, along the length of an alignment. For example, regions of a protein that are exposed to the cytoplasm would tend to be rich in hydrophylic amino acids. In contrast, regions of a protein that due to folding are in the interior of the protein, or membrane spanning regions, would be rich in hydrophobic amino acids.

Further to 1, #2 gives a rationale for different types of substitutions occurring at different frequencies across the length of the alignment. For example, in a transmembrane (hydrophobic) region, substitutions of one hydrophobic aa for another hydrophobic aa would be more common than substitutions of a hydrophilic aa in place of a hydrophobic aa. The reverse would be true in hydrophilic parts of the protein. Put another way, the types of substitutions allowed will vary depending on the function of different parts of a protein.