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Are hinge residues conserved in evolution?
We next investigated whether hinge residues are conserved. Since certain residue classes
are preferred in hinges, one might suspect that hinge residues would be conserved.
Evolutionary conservation can be thought of as an effort to retain genetic features most
important for the survival and proliferation of the species; features that are less essential
are likely to change as a result of random mutations introduced over time through a
variety of mechanisms. If a feature is conserved across related organisms, we say it has
low information entropy, whereas to the extent that its variability approaches random we
say it has high entropy. This entropy is the basis of various measures of information
content, one of which we used and describe below.
First, for each of the Hinge Atlas sequences we wished to find an alignment of protein
sequences similar enough that principal features were conserved, but without large
numbers of proteins so closely related as to be uninformative. To do this we
BLASTed[48] each of the Hinge Atlas sequences against nrdb90, a non-redundant
sequence database in which protein sequences have no more than 90% sequence identity
with each other [22] Next we extracted up to 50 top-aligned sequences to a given morph
to generate a multiple sequence alignment using Clustal W[23]. For each position in the
multiple sequence alignment, we used the formalism developed by Schneider et al[24] to
compute the information content associated with a column in the multiple sequence
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