Comparative genomics of elastin: Sequence analysis of a highly repetitive protein.
Due to the low complexity associated with their sequences, uncovering the evolutionary and functional relationships in highly repetitive proteins such as elastin, spider silks, resilin and abductin represents a significant challenge. Using the polymeric extracellular protein elastin as a model system, we present a novel computational approach to the study of sequence, function and evolutionary relationships in repetitive proteins. To address the absence of accurate sequence annotation for repetitive proteins such as elastin, we have constructed a new database repository, ElastoDB (http://theileria.ccb.sickkids.ca/elastin), dedicated to the storage and retrieval of elastin sequence- and meta-data. To analyse their sequence relationships we have devised an innovative new method, based on the identification of overrepresented 'fuzzy' motifs. Applying this method to elastin sequences derived from mammals, chicken, Xenopus and zebrafish resulted in the identification of both highly conserved, and taxon and species specific motifs that likely represent important functional and/or structural elements. The relative spacing and organization of these elements suggest that exon duplication events have played an important role in the evolution of elastin. Clustering of similarity profiles generated for sets of exons and introns, revealed a pattern of putative duplication events involving exons 15-30 in mammalian and chicken elastins, exons 20-31 in both zebrafish elastins, exons 15-20 in fugu elastin and exons 35-50 in Xenopus elastin 1. The success of this approach for elastin offers a promising route to the elucidation of sequence, structure, function and evolutionary relationships for many other proteins with sequences of low complexity.
He
David
D
Program in Molecular Structure and Function, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario Canada M5G 1X8.
Chung
Martin
M
Chan
Esther
E
Alleyne
Trevis
T
Ha
Kevin C H
KC
Miao
Ming
M
Stahl
Richard J
RJ
Keeley
Fred W
FW
Parkinson
John
J
D000595:Amino Acid Sequence; D000818:Animals; D002645:Chickens; D004549:Elastin / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D011898:Ranidae; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics
D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D004549:Elastin