The purpose of this project is to utilize genomic data from many related organisms in order to learn more about functions of eukaryotic DNA, both coding noncoding. For coding sequences, we developed a method which uses rapid successions of single-nucleotide substitutions at the same codon as an indicator of positive selection, and identified many sites which evolved under such selection in rodent genomes. Also, we developed a method for in silico prediction of whether loss-of-function mutations at a particular gene would be morbid. For non-coding transcribed sequences, we analyzed patterns of evolutionary conservation in 3'UTRs and also developed an algorithm for finding regions of RNAs which are suitable for oligonucleotide targeting. We also continued work on comparative analysis of untranscribed intergenic regions. In particular, we developed an algorithm for calculating evolutionary distances on the basis of indels, instead of substitutions, and studied the dependence of indel mutation rates on their DNA context.
| Yampolsky, Lev Y; Allen, Chenoa; Shabalina, Svetlana A et al. (2005) Persistence time of loss-of-function mutations at nonessential loci affecting eye color in Drosophila melanogaster. Genetics 171:2133-8 |
| Jordan, I King; Kondrashov, Fyodor A; Adzhubei, Ivan A et al. (2005) A universal trend of amino acid gain and loss in protein evolution. Nature 433:633-8 |
| Yampolsky, Lev Y; Kondrashov, Fyodor A; Kondrashov, Alexey S (2005) Distribution of the strength of selection against amino acid replacements in human proteins. Hum Mol Genet 14:3191-201 |
| Kolker, Eugene; Makarova, Kira S; Shabalina, Svetlana et al. (2004) Identification and functional analysis of 'hypothetical' genes expressed in Haemophilus influenzae. Nucleic Acids Res 32:2353-61 |
| Kondrashov, Alexey S; Rogozin, Igor B (2004) Context of deletions and insertions in human coding sequences. Hum Mutat 23:177-85 |
| Arnegard, Matthew E; Kondrashov, Alexey S (2004) Sympatric speciation by sexual selection alone is unlikely. Evolution Int J Org Evolution 58:222-37 |
| Bazykin, Georgii A; Kondrashov, Fyodor A; Ogurtsov, Aleksey Y et al. (2004) Positive selection at sites of multiple amino acid replacements since rat-mouse divergence. Nature 429:558-62 |
| Matveeva, Olga V; Foley, Brian T; Nemtsov, Vladimir A et al. (2004) Identification of regions in multiple sequence alignments thermodynamically suitable for targeting by consensus oligonucleotides: application to HIV genome. BMC Bioinformatics 5:44 |
| Shabalina, Svetlana A; Ogurtsov, Aleksey Y; Rogozin, Igor B et al. (2004) Comparative analysis of orthologous eukaryotic mRNAs: potential hidden functional signals. Nucleic Acids Res 32:1774-82 |
| Kondrashov, Fyodor A; Ogurtsov, Aleksey Y; Kondrashov, Alexey S (2004) Bioinformatical assay of human gene morbidity. Nucleic Acids Res 32:1731-7 |
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