Selection and mutation on the DNA level

Selection and mutation on the DNA level

 

What fraction of all substitutions are fixed by positive selection? What is the rate of mutation in different genomes? What sites in the genome are under negative selection? These fundamental questions are relevant to all aspects of biology, yet we do not have clear answers. We know that most things are under negative selection, positive selection is rare but nor very rare, and that the rate of mutation is small. In the past we have investigated these issues, and in the foreseeable future the efforts of our laboratory will be engaged in elucidating various aspects of selection and mutation on a genomic level. To achieve these aims, it is usually mandatory to  apply or develop  a theoretical background. Using a combination of genome-wide, evolutionary data and theory we have investigated numerous aspects of protein evolution, measured selection in synonymous sites, developed a new test of positive selection and attempted to identify disease-causing and cancer-related genes.

Relevant publications
Schmidt S, Gerasimova A, Kondrashov FA, Adzuhbei IA, Kondrashov AS, Sunyaev S (2008) Hypermutable nonsynonymous sites are under stronger negative selection. PLoS Genet. 4, e1000281.

Assis R, Kondrashov AS, Koonin EV, Kondrashov FA. (2008) Nested genes and increasing organizational complexity of metazoan genomes. Trends Genet. 2008 24, 475-478.

Bazykin GA, Kondrashov FA, Brudno M, Poliakov A, Dubchak I and Kondrashov AS (2007) Extensive parallelism in protein evolution. Biology Direct 2, 20

Babenko VN, Basu MK, Kondrashov FA, Rogozin IB, Koonin EV. (2006) Signs of positive selection of somatic mutations in human cancers detected by EST sequence analysis. BMC Cancer 6, 36.

Kondrashov FA, Ogurtsov AY, Kondrashov AS. (2006) Selection in favor of nucleotides G and C diversifies evolution rates and levels of polymorphism at mammalian synonymous sites. Journal of Theoretical Biology 240, 616-626.

Yampolsky LY, Kondrashov FA and Kondrashov AS. (2005) Strength of selection against amino acid replacements in human proteins. Human Molecular Genetics 14, 3191-3201.

Bazykin GA, Kondrashov FA, Sunyaev S, Ogurtsov AY and Kondrashov AS. (2004) Positive selection at sites of multiple amino acid replacements since rat-mouse divergence. Nature 429, 558-562.

Kondrashov FA, Ogurtsov AY and Kondrashov AS. (2004) Bioinformatical assay of human gene morbidity. Nucleic Acids Res. 32, 1731-1737.

Sunyaev S, Kondrashov FA, Bork P and Ramensky V. (2003) Impact of selection, mutation rate and genetic drift on human genetic variation. Human Molecular Genetics 12, 3325-3330.