Large-scale oscillation of structure-related DNA sequence features in human chromosome 21

Human chromosome 21 is the only chromosome in the human genome that exhibits oscillation of the $(\mathrm{G}+\mathrm{C})$ content of a cycle length of hundreds kilobases (kb) ($500\mathrm{kb}$ near the right telomere). We aim at establishing the existence of a similar periodicity in structure-related sequence features in order to relate this $(\mathrm{G}+\mathrm{C})\%$ oscillation to other biological phenomena. The following quantities are shown to oscillate with the same $500\mathrm{kb}$ periodicity in human chromosome 21: binding energy calculated by two sets of dinucleotide-based thermodynamic parameters, AA/TT and AAA/TTT bi- and tri-nucleotide density, $5^{\prime }\text{−}\mathrm{TA}\text{−}{3}^{\prime }$ dinucleotide density, and signal for 10- or 11-base periodicity of AA/TT or AAA/TTT. These intrinsic quantities are related to structural features of the double helix of DNA molecules, such as base-pair binding, untwisting or unwinding, stiffness, and a putative tendency for nucleosome formation.

Figure 1

(a) $(\mathrm{G}+\mathrm{C})\%$ calculated in nonoverlapping windows of size $2\mathrm{kb}$, (b) free energy $\Delta G$ in the nearest-neighbor model with Breslauer’s parameter values, and (c) free energy $\Delta G$ in the nearest-neighbor model with SantaLucia’s parameter values. The $x$ axis is the chromosome position, in Mb.

Figure 2

(a) Density of AA/TT in nonoverlapping windows of size $2\mathrm{kb}$, (b) AAA/TTT density, (d) $5^{\prime }\text{−}\mathrm{YR}\text{−}{3}^{\prime }$ density, and (d) $5^{\prime }\text{−}\mathrm{TA}\text{−}{3}^{\prime }$ density.

Figure 3

(a) Density of AA-10b-AA/TT-10b-TT in nonoverlapping windows of size $2\mathrm{kb}$, (b) AAA-10b-AAA/TTT-10b-TTT density, and (c) YWG-10b-VWG density, where VWG indicates [not-T][A/T][G] or its reverse complement triplet [C][A/T][not-A].

Figure 4

Scatter plots of ten quantities versus GC%: (a) helix binding energy by the model of Breslauer et al., (b) binding energy by SantaLucia’s model, (c) AA/TT (upper) and AAA/TTT (lower, using the symbol $\mid$) densities, (d) $5^{\prime }\text{−}\mathrm{YR}\text{−}{3}^{\prime }$ density, (e) $5^{\prime }\text{−}\mathrm{TA}\text{−}{3}^{\prime }$ densities, (f) AA-10b-AA/TT-10b-TT (upper) and AAA-10b-AAA/TTT-10b-TTT (lower, using the symbol $\mid$) densities, (g) VWG-10-VWG densities, and (h) density of the top 34 hexamers in known S/MAR sequences and their reverse complements. The corresponding values for randomized sequences are also shown (grey circles). The correlation coefficient between these quantities and GC% is indicated on the plot.