The Laboratory of Computational Molecular Biology. Professor Alexander Bolshoy.

The major goal is to reveal biological role of certain evolutionary preserved genomic patterns using statistical and other methods of sequence comparison. The four topics of major investigations are: (1) evolution of noncoding DNA; (2) evolution of retroviruses; (3) chromatin organization; (4) genomic sequence repeats.

1. Evolution of Promoters.

Currently we continue study started in ^1-3. In the latter manuscript "Ecological genomics of DNA: upstream bending in prokaryotic promoters" we analyzed the distribution of predicted intrinsic curvature along all complete bacterial genomes. We found that the DNA curvature plays a biological role in gene regulation in mesophilic as against hyperthermophilic prokaryotes, i.e. DNA curvature presumably has a functional adaptive significance determined by temperature selection.

2. Factors of Sequence Conservation in HIV-1 Genome.

Using algorithms for computing the optimal RNA folding patterns on a data set of env sequences of HIV-1 we found conserved RNA secondary structure in the C1 region ⁸. We also analyzed the variability of putative RNA secondary structures inside the nef gene of HIV-1 by applying these algorithms to a non-redundant data set of 104 nef sequences, and predicted the existance of a novel functional RNA secondary structure in b3/b4 regions of nef. The predicted RNA fold in b3/b4 region of nef appears in two forms, withh different loop sizes.

3. Nucleosome DNA sequence pattern.

We plan to continue our study started in ^4-7

4. Sequence complexity.

The manuscript "Sequence Complexity Profiles of Prokaryotic Genomic Sequences: A Fast Algorithm for Calculating Linguistic Complexity." of Troyanskaya O.G., Arbell O., Koren Y., Landau G.M. and Bolshoy A. has been published in Bionformatics in May 2002.

References.

1. Gabrielian, A.E. & Bolshoy, A. Sequence complexity and DNA curvature. Comput Chem. 23, 263-274 (1999).

2. Gabrielian, A.E., Landsman, D. & Bolshoy, A. Curved DNA in promoter sequences. In Silico Biol. 1, 183-196, (1999).

3. Bolshoy, A. & Nevo, E. Ecologic genomics of DNA: upstream bending in prokaryotic promoters. Genome Res. 10, 1185-1193 (2000).

4. Ioshikhes, I., Bolshoy, A., Derenshteyn, K., Borodovsky, M. & Trifonov, E.N. Nucleosome DNA sequence pattern revealed by multiple alignment of experimentally mapped sequences. J Mol Biol 262, 129-139 (1996).

5. Bolshoy, A. CC dinucleotides contribute to the bending of DNA in chromatin. Nat Struct Biol. 2, 446-448 (1995).

6. Bolshoy, A., Ioshikhes, I. & Trifonov, E.N. Applicability of the multiple alignment algorithm for detection of weak patterns: periodically distributed DNA pattern as a study case. Comput Appl Biosci. 12, 383-389 (1996).

7. Bolshoy, A., Shapiro, K., Trifonov, E.N. & Ioshikhes, I. Enhancement of the nucleosomal pattern in sequences of lower complexity. Nucl. Acids Res 25, 3248- 3254 (1997).

8. Peleg, O., Brunak, S., Trifonov, E.N., Nevo, E. & Bolshoy, A. RNA secondary structure and sequence conservation in C1 region of human Immunodeficiency virus type 1 env gene. AIDS research and Human Retroviruses 18, 867-878 (2002).

9. Troyanskaya, O.G., Arbell, O., Koren, Y., Landau, G.M. & Bolshoy, A. Sequence complexity profiles of prokaryotic genomic sequences: a fast algorithm for calculating linguistic complexity. Bioinformatics 18, 679-688 (2002).