The principal sequence feature responsible for intrinsic DNA curvature is generally assumed to be runs of adenines. However, according to the wedge model of DNA curvature, each dinucleotide step is associated with a characteristic deflection of the local helix axis. Thus, an important test of a more general view of sequence-dependent DNA curvature is whether sequence elements other than A-A cause the DNA axis to deflect. To address this question, we have applied the wedge model to a large body of experimental data. The axial path of DNA can be described at each step by three Eulerian angles: the helical twist, the deflection angle (wedge angle), and the direction of the deflection. Circularization and gel electrophoretic mobility data on 54 synthetic DNA fragments, both from other laboratories and from our own, were used to compare the theoretical predictions of the wedge model with experiment. By minimizing misfit between calculated and observed DNA curvature, we have found that the stacks AG/CT, CG/CG, GA/TC, and GC/GC, in addition to AA/TT, have large wedge values. We have also synthesized seven sequences without AA/TT elements but with these other wedges correctly phased to cause appreciable predicted curvature. All appear curved as demonstrated by anomalous gel mobilities. The full set of 16 roll and tilt wedge angles is estimated and, together with the known 10 helical twists, these allow prediction of the general sequence-dependent trajectory of the DNA axis.

A correlation analysis of chromatin DNA nucleotide sequences reveals the clear tendency of some of the dinucleotides to be repeated along the sequences with periods of 3 and about 10.5 bases. This latter period, which is equal within experimental error to recent estimates of the pitch of the DNA double helix

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Temporal order ("chronology") of appearance of amino acids and their respective codons on evolutionary scene is reconstructed. A consensus chronology of amino acids is built on the basis of 60 different criteria each offering certain temporal order. After several steps of filtering the chronology vectors are averaged resulting in the consensus order: G, A, D, V, P, S, E, (L, T), R, (I, Q, N), H, K, C, F, Y, M, W. It reveals two important features: the amino acids synthesized in imitation experiments of S. Miller appeared first, while the amino acids associated with codon capture events came last. The reconstruction of codon chronology is based on the above consensus temporal order of amino acids, supplemented by the stability and complementarity rules first suggested by M. Eigen and P. Schuster, and on the earlier established processivity rule. At no point in the reconstruction the consensus amino-acid chronology was in conflict with these three rules. The derived genealogy of all 64 codons suggested several important predictions that are confirmed. The reconstruction of the origin and evolutionary history of the triplet code becomes, thus, a powerful research tool for molecular evolution studies, especially in its early stages.

Curved DNA molecules and unusually small circles have been obtained by ligation of synthetic 21-base precursors:The ligation resulted in the formation of double-stranded oligo-(precursor)s possessing a strong 10.5-base-pair (bp) periodicity of the runs of adenines. Two-dimensional polyacrylamide gel electrophoresis of the ligation products showed two distinct families of spots: (a) noncircular oligo(precursor)s of 21 to 231 bp (1-to ll-mers) and (it) four circles from 105 to 168 bp (eluted and analyzed by denaturing gel electrophoresis). The noncircular oligomers exhibited anomalously slow migration, as if they were as much as three times longer than they actually are. The amount of circular products peaked sharply at %126 bp, near which size the circles have been estimated to be nonconstrained both torsionally and in terms of bending. The nonconstrained circularization provides a technique for the direct measurement of the inherent curvature of DNA in solution. From the size of the circles, an estimate of 8.7 is obtained for the absolute value of the AA-TT wedge angle (roll and tilt combined).The "wedge" model of inherently curved DNA was suggested (1, 2) on the basis of a weak 10.5-base-pair (bp) periodicity observed in chromatin DNA sequences and is shown in Fig.