Institute of Cytology, Russian Academy of Sciences
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Abstract |
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Introduction |
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Materials and Methods |
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The random DNA sequences of 10-kb length were generated with 0.1% increments in the 1%100% range of GC-content using Perl function rand. (Each base pair was drawn by two iterations, one for choice between the GC and AT pairs, and the other for choice between the purine and pyrimidine bases on a given strand. The real percent of GC-pairs and purine bases on a given strand was determined after the generation of the sequence.) Generally, the average content of purine bases on the coding strand in exons is about 48%, and in introns, about 52%. Therefore, the complete sets of random sequences were generated for different purine contents in the range of 45%55% (with 2.5% increments); their bendability and melting energy were not found to vary significantly. Here, the results for the 50% purine content are presented.
The parameters under study were determined using the trinucleotide table for bendability based on consensus values obtained from the DNAse I digestion and nucleosome positioning studies (Gabrielian, Simoncsits, and Pongor 1996
) and the dinucleotide table for free energy of melting (delta G) obtained from the UV absorbance and temperature profiles (SantaLucia, Allawi, and Seneviratne 1996
) in a sliding tri- and dinucleotide frame (with 1 - nt step), respectively, and averaged for each sequence.
The statistical analyses were done with the Statgraphics (Statistical Graphics Co.) and Statistica (StatSoft, Inc.) software.
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Results |
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With only a few exceptions (exons of the rat, introns and exons of a green alga), there is a negative partial correlation between the bendability and melting energy at fixed GC-percent (table 1 ). This correlation is always stronger in the introns as compared with exons. (The coefficients of partial correlation between the polynomial-subtracted residuals of bendability and melting energy at fixed GC-percent were very similar and not shown.)
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Discussion |
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Genome compositional heterogeneity is known to be lower in the murids as compared with other mammals (Robinson, Gautier, and Mouchiroud 1997
; Douady et al. 2000
). The compositional heterogeneity was found not only in the homeotherms, but also, to a lesser degree, in the lower animals (D'Onofrio et al. 1999
; Jabbari and Bernardi 2000
; Nekrutenko and Li 2000
) and plants as well. Among the latter, it is most pronounced in the cereals but can be discerned also in the cress thale (Carels and Bernardi 2000
; Nekrutenko and Li 2000
). The present results suggest that in all these cases, except in cereals, this heterogeneity may be stipulated by the increase in bendability of GC-rich genome regions. The cereals differ from the homeotherms by a much higher exon-intron contrast in GC-content (Carels et al. 1998
; Vinogradov 2001
) and may present a special case. If these physical DNA properties are involved somehow in the GC-enrichment of cereal genomes, it is either the melting energy that may be a leading cause or there is some subtle balance between the two forces.
Although the GC-rich regions constitute only a minor part of the genome (10%15%), they harbor a great part of the genes because of the very high gene concentration (Bernardi 2000
). They are located in the early replicating and highly transcribed chromatin (Saccone et al. 1993, 1999
; Federico, Saccone, and Bernardi 1998
). Therefore, the DNA helix of these genes should be often bent and unbent in its transition from packaged to extended state to comply with the operation of transcription machinery. These requirements should extend both to the exons and introns and probably to the intergenic sequences as well (which are short and also GC-rich in the heavy isochores). The average molecular properties were suggested to dominate over the local features in the sequence-dependent nucleosome formation (Anselmi et al. 2000
). It was supposed that introns can be necessary for correct chromatin structure (Zuckerkandl 1981
; Trifonov 1993
). In several cases, the involvement of introns in the nucleosome ordering was demonstrated experimentally (Lauderdale and Stein 1992
; Liu et al. 1995
). Therefore, it is interesting that the bendability over melting energy trend is more pronounced in the introns of the homeotherms as compared with their exons (table 1). In a seeming contradiction to the notion about possible significance of intronic bendability for the structure of chromatin, there is the fact that introns in the heavy isochores are GC-poorer than exons (e.g., Bernardi 2000
; Vinogradov 2001
). However, this can be explained by the impact of transposable elements, which decreases GC-content of introns even when these elements become nonrecognizable (Duret and Hurst 2001
). The increase in the bendability of the highly expressed genes of mammals and birds may be associated with the higher organizational level of these animals, which requires fast and smoothly operating transcription.
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Acknowledgements |
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Footnotes |
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Keywords: isochore
mutation bias
GC-percent
bendability
thermal stability
introns
Address for correspondence and reprints: Alexander E. Vinogradov, Institute of Cytology, Russian Academy of Sciences, Tikhoretsky Ave. 4, St. Petersburg 194064, Russian Federation. aevin{at}mail.cytspb.rssi.ru
.
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References |
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