Evolutionarily consistent families in SCOP: sequence, structure and function

Several phylogenetic trees were generated for each superfamily: one derived from a multiple sequence alignment, one based on structural distances, and the final two from presence/absence of GO terms or EC numbers assigned to domains. The topologies of the resulting trees and confidence values were compared to the SCOP family classification.We show that SCOP family groupings are evolutionarily consistent to a very high degree with respect to classical sequence phylogenetics. The trees built from (automatically generated) structural distances correlate well, but are not always consistent with SCOP (hand annotated) groupings. Trees derived from functional data are less consistent with the family level than those from structure or sequence, though the majority still agree. Much of GO and EC annotation applies directly to one family or subset of the family; relatively few terms apply at the superfamily level. Maximum sequence diversity within a family is on average 22% but close to zero for superfamilies.Proteins are made up of domains. Protein domains in this context can be regarded as the building blocks of proteins, and the smallest units of protein evolution. A small protein may consist of a single domain, larger proteins maybe contain multiple domains. A domain can be defined as a protein unit which is seen in nature either on its own or in combination with other different domains.Detecting the evolutionary relationship between two or more domains using sequence information alone is often not possible, as sequences often diverge beyond the point of detection by comparison methods. Lack of sequence information does not necessarily show that there is no relationship between domains. If the three dimensional structure of the domains is known, evolutionary relationships can usually be recognised. The Structural Classification of Proteins (SCOP) [1-3], is a hierarchical classification system of proteins for which atomic resolution three dimensional structures are known;