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Ariel Fernandez (2011) Nonadaptive Origins of Interactome Complexity. Nature, volume 474, pages 502-505.
This work by Ariel Fernandez (formerly also by Michael Lynch) highlights the pivotal role of dehydrons - the epistructural markers of protein association- in molecular evolution. While the fold is conserved across proteins of common ancestry, Ariel Fernandez shows here that the associated dehydron pattern is not conserved, and in fact changes in a manner that reveals the role of random genetic drift as promoter of interactome complexity. The nonconserved nature of dehydron patterns across homologs has been exploited in the past at Ariel Fernandez Consultancy in order to build selectivity filters for drug design and molecular targeted therapy. The selectivity filter materializes through the so-called wrapping technology, a drug design strategy introduced by Ariel Fernandez in 2005.
Sampling bias in small populations can result in a non-adaptive evolutionary phenomenon called genetic drift. By comparing the protein-coding genomes of many species, Ariel Fernandez and Michael Lynch show that population-size bottlenecks allow for the appearance of mildly destabilized proteins that can subsequently be re-stabilized through new protein–protein interactions. These interactions can then evolve into meaningful biochemical pathways. Thus, although complex protein architectures and interactions may be essential contributors to phenotypic complexity, such features may initially emerge through non-adaptive mechanisms.