The appearance of new structures and functions in proteins during evolution.

The likelihood of a de novo generation of classes of efficient proteins through neoformation of DNA, through modification of expressed DNA, and through modification of nonexpressed DNA is examined. So is the likelihood that newly formed inefficient enzymes be turned into efficient enzymes. The conclusions are that neither gene duplicates nor dormant genes represent promising materials for a de novo generation of protein classes, that (with exceptions) such generation is unlikely to have taken place in recent evolution, that new structural genes must nearly consistently derive from preexisting structural genes, and that new functions can be evolved only on the basis of old proteins. Conditions of protein evolution in prokaryotes suggest that the saltatory formation of protein classes is as unlikely in prokaryotes as in eukaryotes. Data on the history of a few protein classes are reviewed to illustrate the preceding inferences. The analysis leads to the hypothesis that most protein classes originated before the major elements of the translation apparatus of modern cells were fully evolved. If simple sequence DNA is turned into structural genes by evolution, this process (again with exceptions) is considered to have taken place only at that very remote period. A polyphyletic origin of proteins is thought to date back to the same era. It is proposed that the development of genic multiplicity and of marked structural and functional diversity of proteins may have come about in the earliest cells primarily through the independent generation of structurally different polymerases in different protocells, followed by cell conjugation and the subsequent use by enriched cells of supernumerary types of polymerase for evolving further functions. Functional growth, as it took place at early times, is briefly discussed as well as functional change. The foundations for new functional developments in old proteins are analyzed. In considering the evolutionary recovery of lost functions, aspects of cell differentiation and gene regulation are linked with the evolutionary picture. The distinction between eurygenic and stemogenic control of gene activity is used. Next to gene deletion, cell and tissue deletion is held to be an event of general evolutionary significance, through cell and tissue origination that presumably accompanies the restoration of a lost molecular function.