DNA shape, genetic codes, and evolution

Abstract

Although the three-letter genetic code that maps nucleotide sequence to protein sequence is well known, there must exist other codes that are embedded in the human genome. Recent work points to sequence-dependent variation in DNA shape as one mechanism by which regulatory and other information could be encoded in DNA. Recent advances include the discovery of shape-dependent recognition of DNA that depends on minor groove width and electrostatics, the existence of overlapping codes in protein-coding regions of the genome, and evolutionary selection for compensatory changes in nucleotide composition that facilitate nucleosome occupancy. It is becoming clear that DNA shape is important to biological function, and therefore will be subject to evolutionary constraint.

Figure 1

Different genomic codes are subject to selective pressures. Shown is a hypothetical genomic region (top) with a gene (black rectangle), nucleosomes (red ellipses), and various transcription factors (colored circles). Gray rectangles (middle) represent genomic regions in which the primary order of the DNA nucleotide sequence encodes functional information. Pink rectangles (bottom) represent regions where genomic information is encoded in DNA shape. These various encodings can be dispersed, overlapping, redundant, and, importantly, can represent different types of biological function. Considering the molecular structure of DNA in addition to the primary nucleotide sequence can help in understanding how biological function is encoded in genomes. Note that symbols and spacing are not drawn to scale.

Figure 2

Three-dimensional structure of the DNA minor groove. The minor groove of a B-form DNA molecule (PDB code: 355D) is shown in this Chimera rendering. The backbone is represented as a ribbon and the bases as a ladder. The numbering system corresponds to nucleotides that are either complementary (i and i’), or offset by different numbers of nucleotides across the strands, in the 3′ direction. The red arrows point toward the 3′ end of each strand. Distances between C5′ atoms on each strand are depicted with yellow lines. Note that the C5′ atoms closest to each other across the two DNA strands belong to nucleotides offset by +3 and +4. (This figure was adapted from Jason A Greenbaum, PhD thesis, Boston University, 2006, and used with permission.)

Figure 3

The relationship between sequence identity and similarity in structural profile in a pairwise comparison of all 7-mer DNA oligonucleotide duplexes. DNA structural profiles were predicted using the ORChID database [21], and similarity in structure was measured using Euclidean distance. The color scale represents log₁₀(counts) for each cell within the matrix, representing the number of sequences having a particular nucleotide sequence identity and a particular structural similarity. The cell in the lower left corner, which corresponds to sequences with 0% identity but very similar structural profiles, contains 1,365 distinct 7-mer pairs. The overall correlation (Pearson’s r) between sequence identity and structural profile change is −0.365.