BACKGROUND: The substitution rates within different nucleotide contexts are subject to varying levels of bias. The most well known example of such bias is the excess of C to T (C > T) mutations in CpG (CG) dinucleotides. The molecular mechanisms underlying this bias are important factors in human genome evolution and cancer development. The discovery of other nucleotide contexts that have profound effects on substitution rates can improve our understanding of how mutations are acquired, and why mutation hotspots exist. RESULTS: We compared rates of inherited mutations in 1-4 bp nucleotide contexts using reconstructed ancestral states of human single nucleotide polymorphisms (SNPs) from intergenic regions. Chimp and orangutan genomic sequences were used as outgroups. We uncovered 3.5 and 3.3-fold excesses of T > C mutations in the second position of ATTG and ATAG words, respectively, and a 3.4-fold excess of A > C mutations in the first position of the ACAA word. CONCLUSIONS: Although all the observed biases are less pronounced than the 5.1-fold excess of C > T mutations in CG dinucleotides, the three 4 bp mutation contexts mentioned above (and their complementary contexts) are well distinguished from all other mutation contexts. This provides a challenge to discover the underlying mechanisms responsible for the observed excesses of mutations.

UNLABELLED: The database NPIDB (Nucleic Acids-Protein Interaction DataBase) contains information derived from structures of DNA-protein and RNA-protein complexes extracted from PDB (1834 complexes in July 2007). It is organized as a collection of files in PDB format and is equipped with a web-interface and a set of tools for extracting biologically meaningful characteristics of complexes. The content of the database is weekly updated. AVAILABILITY: http://monkey.belozersky.msu.ru/NPIDB/