ON THE RECOMBINATIONAL ORIGIN OF PROTEIN-SEQUENCE-SUBUNIT STRUCTURE

Since 1929 the concept that proteins are built from subunits of certain standard size (Svedberg 1929) has been revisited several times, each time with a new demonstration that, indeed, there are certain preferred protein sizes. According to recent estimates the overrepresented sizes are close to multiples of 125 amino acid (aa) residues for eukaryotes and 150 residues for prokaryotes. To explain these preferences, a hypothesis is suggested, and quantitatively developed, on the recombinational nature of this regularity. The protein-coding sequences are assumed to evolve at some early stage via recombinational events-insertions of DNA circles of a certain optimal size. The contour lengths of the protein-coding DNA circles had to be simultaneously divisible by three and, to minimize torsional constraint, by the DNA helical repeat. With these two conditions satisfied, the calculated contour lengths of the DNA circles, 250-500 base pairs (bp), turn out to correspond well to known optimal DNA circularization sizes and to the predicted range of the protein sequence subunit sizes: 80-170 aa residues, which covers experimentally observed values. The subunit size is found to be strongly influenced by the helical repeat of DNA. The sizes 125 and 150 aa are derived when the corresponding helical repeats of DNA are set within fractions of promilles from the 10.54 bp/turn value. This fits to the experimentally estimated mean for natural mixed DNA sequences, 10.53-10.57 bp/turn. The suggested recombinational mechanism thus not only gives a qualitative explanation for the observed underlying order in the protein sequences but also quantitatively links the observed protein sequence sizes with the optimal DNA circularization size and with the helical repeat of DNA. It also offers a versatile molecular model of early protein evolution by fusion and insertion of preexisting proteins of standard subunit sizes.