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Homologues, analogues and evolution

As a result of classification efforts, two main terms are used to describe pairs of protein structures with similar folds:

• Homologous: same fold, same or similar function, common ancestry.
• Analogous: same fold, different function, ancestral origin unknown.

Since homology is defined by common ancestry it is not a difficult concept to take hold of. However `common ancestry' does not necessarily infer `detectable sequence similarity' (see Section 1.4.1). Correctly aligned homologues can share minimal sequence identity in the range of about 0-25% known as the `twilight zone' of sequence similarity[Doolittle, 1981,Sander & Schneider, 1991]. Pairs of analogues also align with very low sequence identity, however this is obviously not sufficient evidence to rule out evolutionary relatedness. Many proteins have been evolving for a billion or more years and their sequences have diverged beyond recognition. There has also been sufficient time for the spontaneous evolution of the same folds in unrelated proteins (convergent evolution). In this context, a number of commonly occurring folds[Orengo et al., 1994] may be `attractors' in fold space. For example, the TIM barrel topology[Farber, 1993,Orengo et al., 1994,Reardon & Farber, 1995] has an eightfold strand-helix repeat which may have simpler folding pathways and could also be the common outcome of gene duplication events.