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. Also we found that within the V3 region, the conservation of nucleotides at the gene level is substantially higher than the conservation of amino acids at the protein level.

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 submitted to Bionformatics in January 2001.

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).