title: SNPs occur in regions with less genomic sequence conservation.
abstract: Rates of SNPs (single nucleotide polymorphisms) and cross-species genomic sequence conservation reflect intra- and inter-species variation, respectively. Here, I report SNP rates and genomic sequence conservation adjacent to mRNA processing regions and show that, as expected, more SNPs occur in less conserved regions and that functional regions have fewer SNPs. Results are confirmed using both mouse and human data. Regions include protein start codons, 3' splice sites, 5' splice sites, protein stop codons, predicted miRNA binding sites, and polyadenylation sites. Throughout, SNP rates are lower and conservation is higher at regulatory sites. Within coding regions, SNP rates are highest and conservation is lowest at codon position three and the fewest SNPs are found at codon position two, reflecting codon degeneracy for amino acid encoding. Exon splice sites show high conservation and very low SNP rates, reflecting both splicing signals and protein coding. Relaxed constraint on the codon third position is dramatically seen when separating exonic SNP rates based on intron phase. At polyadenylation sites, a peak of conservation and low SNP rate occurs from 30 to 17 nt preceding the site. This region is highly enriched for the sequence AAUAAA, reflecting the location of the conserved polyA signal. miRNA 3' UTR target sites are predicted incorporating interspecies genomic sequence conservation; SNP rates are low in these sites, again showing fewer SNPs in conserved regions. Together, these results confirm that SNPs, reflecting recent genetic variation, occur more frequently in regions with less evolutionarily conservation.
authors.affiliation: Rosetta Inpharmatics LLC, Seattle, Washington, United States of America. john.castle@tron-mainz.de
authors.forename: John C
authors.initials: JC
authors.lastname: Castle
mesh_terms: D000818:Animals; D001665:Binding Sites; D018387:Codon, Initiator / Q000235:genetics; D018388:Codon, Terminator / Q000235:genetics; D017124:Conserved Sequence; D019143:Evolution, Molecular; D015894:Genome, Human / Q000235:genetics; D023281:Genomics; D006801:Humans; D007438:Introns / Q000235:genetics; D051379:Mice; D026723:Polyadenylation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D022821:RNA Splice Sites / Q000235:genetics; D012326:RNA Splicing / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D018387:Codon, Initiator; D018388:Codon, Terminator; D022821:RNA Splice Sites