Published online before print
November 21, 2000, 10.1101/gr.GR-1478R
Vol. 10, Issue 12, 1845-1864, December 2000
Phylogeny of the Serpin Superfamily: Implications of Patterns of Amino Acid Conservation for Structure and Function
James A.
Irving,1
Robert N.
Pike,1
Arthur M.
Lesk,2 and
James C.
Whisstock1,3
1 Department of Biochemistry and Molecular Biology, Monash
University, Clayton Campus, Melbourne, Victoria 3168, Australia;
2 Wellcome Trust Centre for the Study of Molecular Mechanisms
in Disease, Cambridge Institute for Medical Research, University of
Cambridge Clinical School, Cambridge CB2 2XY, United Kingdom
We present a comprehensive alignment and phylogenetic analysis of
the serpins, a superfamily of proteins with known members in higher
animals, nematodes, insects, plants, and viruses. We analyze, compare,
and classify 219 proteins representative of eight major and eight minor
subfamilies, using a novel technique of consensus analysis. Patterns of
sequence conservation characterize the family as a whole, with a clear
relationship to the mechanism of function. Variations of these patterns
within phylogenetically distinct groups can be correlated with the
divergence of structure and function. The goals of this work are to
provide a carefully curated alignment of serpin sequences, to describe
patterns of conservation and divergence, and to derive a phylogenetic
tree expressing the relationships among the members of this family. We
extend earlier studies by Huber and Carrell as well as by Marshall, after whose publication the serpin family has grown functionally, taxonomically, and structurally. We used gene and protein sequence data, crystal structures, and chromosomal location where available. The
results illuminate structure-function relationships in serpins, suggesting roles for conserved residues in the mechanism of
conformational change. The phylogeny provides a rational evolutionary
framework to classify serpins and enables identification of conserved
amino acids. Patterns of conservation also provide an initial point of
comparison for genes identified by the various genome projects. New
homologs emerging from sequencing projects can either take their place
within the current classification or, if necessary, extend it.
3
Corresponding author.
10:1845-1864 ©2000 by Cold Spring Harbor Laboratory Press ISSN 1088-9051/00 $5.00
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