On the possibility of the production of many rare proteins by higher eukaryotes

Arguments are presented which support the idea that the large amount of single copy DNA in the haploid genome of higher eukaryotes is coding for many (approximately 10(6) rare proteins, that is, proteins present at the level of no more than a few molecules per cell. It is asserted that a large number of such rare protein species is consistent with (1) apparent slow rates of DNA sequence evolution as shown by DNA annealing experiments, (2) physiological complexity and the DNA content of organisms, and (3) evidence that there are many proteins already known whose primary purpose is the regulation of the function of other proteins. It is shown that the best available detection techniques would not uncover these proteins unless a concerted effort were made to do so. An outline of such an effort, based on immune precipitation and two-dimensional gel electrophoresis, is presented and discussed.