Mutation processes at the protein level: is Lamarck back?

The experimental evidence accumulated for the last half of the century clea rly suggests that inherited variation is not restricted to the changes in g enomic sequences. The prion model, originally based on unusual transmission of certain neurodegenerative diseases in mammals, provides a molecular mec hanism for the template-like reproduction of alternative protein conformati ons. Recent data extend this model to protein-based genetic elements in yea st and other fungi. Reproduction and transmission of yeast protein-based ge netic elements is controlled by the "prion replication" machinery of the ce ll, composed of the protein helpers responsible for the processes of assemb ly and disassembly of protein structures and multiprotein complexes. Among these, the stress-related chaperones of Hsp100 and Hsp70 groups play an imp ortant role. Alterations of levels or activity of these proteins result in "mutator" or "antimutator" affects in regard to protein-based genetic eleme nts. "Protein mutagens" have also been identified that affect formation and /or propagation of the alternative protein conformations. Prion-forming abi lities appear to be conserved in evolution, despite the divergence of the c orresponding amino acid sequences. Moreover, a wide variety of proteins of different origins appear to possess the ability to form amyloid-like aggreg ates, that in certain conditions might potentially result in prion-like swi tches. This suggests a possible mechanism for the inheritance of acquired t raits, postulated in the Lamarckian theory of evolution. The prion model al so puts in doubt the notion that cloned animals are genetically identical t o their genome donors, and suggests that genome sequence would not provide a complete information about the genetic makeup of an organism. (C) 2001 El sevier Science B.V. All rights reserved.