Bifractality of human DNA strand-asymmetry profiles results from transcription

S. Nicolay, E. B. Brodie of Brodie, M. Touchon, B. Audit, Y. d’Aubenton-Carafa, C. Thermes, and A. Arneodo

Phys. Rev. E 75, 032902 – Published 12 March 2007

Abstract

We use the wavelet transform modulus maxima method to investigate the multifractal properties of strand-asymmetry DNA walk profiles in the human genome. This study reveals the bifractal nature of these profiles, which involve two competing scale-invariant (up to repeat-masked distances $≲ 40 kbp$ ) components characterized by Hölder exponents $h_{1} = 0.78$ and $h_{2} = 1$ , respectively. The former corresponds to the long-range-correlated homogeneous fluctuations previously observed in DNA walks generated with structural codings. The latter is associated with the presence of jumps in the original strand-asymmetry noisy signal $S$ . We show that a majority of upward (downward) jumps colocate with gene transcription start (end) sites. Here 7228 human gene transcription start sites from the refGene database are found within $2 kbp$ from an upward jump of amplitude $Δ S ⩾ 0.1$ which suggests that about 36% of annotated human genes present significant transcription-induced strand asymmetry and very likely high expression rate.

Received 8 July 2006

DOI:https://doi.org/10.1103/PhysRevE.75.032902

Authors & Affiliations

S. Nicolay^1,*, E. B. Brodie of Brodie¹, M. Touchon², B. Audit¹, Y. d’Aubenton-Carafa², C. Thermes², and A. Arneodo¹

¹Laboratoire Joliot-Curie and Laboratoire de Physique, UMR 5672, CNRS, ENS-Lyon, 46 Allée d’Italie, 69364 Lyon Cedex 07, France
²Centre de Génétique Moléculaire, UPR 2167 CNRS, Allée de la Terrasse, 91198 Gif-sur-Yvette, France

^*Permanent address: Institut de Mathématique, Université de Liège, Grande Traverse 12, 4000 Liège, Belgium

Article Text (Subscription Required)

Click to Expand

References (Subscription Required)

Click to Expand

Issue

Vol. 75, Iss. 3 — March 2007

Reuse & Permissions

Access Options

Author publication services for translation and copyediting assistance advertisement

Images

Figure 1
(a) Skew profile $S (n)$ of a repeat-masked fragment of human chromosome 6; light gray (dark gray) $1 − kbp$ window points correspond to sense (antisense) genes lying on the Watson (Crick) strand; black points to intergenic regions. (b) Cumulated skew profile $Σ (n)$ . (c) WT of $Σ$ ; $T_{ψ^{(2)}} (n, a)$ is coded from white (min) to black (max); the WT skeleton defined by the maxima lines is shown in solid (dashed) lines corresponding to positive (negative) WT values. For illustration black solid (dashed) maxima lines are shown to point to the positions of 4 upward (3 downward) jumps in $S$ [vertical dashed lines in (a) and (b)] that coincide with gene transcription starts (ends). Thick white lines correspond to maxima lines that persist above $a ⩾ 200 kbp$ and that point to sharp upward jumps in $S$ [vertical solid lines in (a) and (b)] that are likely to be the locations of putative replication origins [12]; note that three out of those four jumps are colocated with transcription start sites.Reuse & Permissions
Figure 2
Multifractal analysis of $Σ (n)$ of the 22 human (solid symbols) and 19 mouse (open circles) autosomes using the WTMM method with $ψ^{(2)}$ over the range $10 kbp ⩽ a ⩽ 40 kbp$ . (a) $τ (q)$ vs $q$ . (b) $D (h)$ vs $h$ . (c) WTMM pdf: $ρ$ is plotted versus $∣ T ∣ ∕ a^{H}$ where $H = h_{1} = 0.78$ , in semilogarithmic representation; the inset is an enlargement of the pdf central part in linear representation. (d) Same as in (c) but with $H = h_{2} = 1$ . In (c) and (d), the symbols correspond to scales $a = 10$ (●), 20 (∎), and 40 (▴) kbp.Reuse & Permissions
Figure 3
Statistical analysis of skew variations at the singularity positions determined at scale $1 kbp$ from the maxima lines that exist at scales $a ⩾ 10 kbp$ in the WT skeletons of the 22 human autosomes. For each singularity, we computed the variation amplitudes $Δ S = \bar{S} (3^{'}) - \bar{S} (5^{'})$ over two adjacent $5 − kbp$ windows, respectively in the $3^{'}$ and $5^{'}$ directions and the distances $Δ n$ to the closest TSS (TES). (a) Histograms $N (∣ Δ S ∣)$ for upward ( $Δ S > 0$ , gray) and downward ( $Δ S < 0$ , black) skew variations. (b) Histograms of the distances $Δ n$ of upward (gray) or downward (black) jumps with $∣ Δ S ∣ ⩾ 0.1$ to the closest TSS (filled black bullet, filled gray bullet) and TES (empty black circle, empty gray circle).Reuse & Permissions
Figure 4
(a) Number of TSS’s with an upward jump within $∣ Δ n ∣$ (abscissa) for jump amplitudes $Δ S > 0.1$ (black), 0.15 (dark gray), and 0.2 (light gray). Solid lines correspond to true jump positions while dashed lines to the same analysis when jump positions were randomly drawn along each chromosome. (b) Among the $N_{tot} (Δ S^{*})$ upward jumps of amplitude larger than some threshold $Δ S^{*}$ , we plot the proportion of those that are found within $1 kbp$ (●), $2 kbp$ (∎), or $4 kbp$ (▴) of the closest TSS vs the number $N_{TSS}$ of the so-delineated TSS’s. Curves were obtained by varying $Δ S^{*}$ from 0.1 to 0.3 (from right to left). Open symbols correspond to similar analyses performed on random upward jump and TSS positions.Reuse & Permissions

Physical Review E

covering statistical, nonlinear, biological, and soft matter physics