the evolution of extracellular fibrillins and their functional domains细胞外的进化fibrillins及其功能域.pdfVIP

The Evolution of Extracellular Fibrillins and Their Functional Domains 1 2 1,3 Adam Piha-Gossack , Wayne Sossin , Dieter P. Reinhardt * 1 Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada, 2 Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada, 3 Faculty of Dentistry, McGill University, Montreal, Quebec, Canada Abstract Fibrillins constitute the major backbone of multifunctional microfibrils in elastic and non-elastic extracellular matrices, and are known to interact with several binding partners including tropoelastin and integrins. Here, we study the evolution of fibrillin proteins. Following sequence collection from 39 organisms representative of the major evolutionary groups, molecular evolutionary genetics and phylogeny inference software were used to generate a series of evolutionary trees using distance-based and maximum likelihood methods. The resulting trees support the concept of gene duplication as a means of generating the three vertebrate fibrillins. Beginning with a single fibrillin sequence found in invertebrates and jawless fish, a gene duplication event, which coincides with the appearance of elastin, led to the creation of two genes. One of the genes significantly evolved to become the gene for present-day fibrillin-1, while the other underwent evolutionary changes, including a second duplication, to produce present-day fibrillin-2 and fibrillin-3. Detailed analysis of several sequences and domains within the fibrillins reveals distinct similarities and differences across various species. The RGD integrin-binding site in TB4 of all fibrillins is conserved in cephalochordates a