Estimation of genetic distances from human and mouse introns.docVIP

/2002/3/6/research/0028.1 Research Estimation of genetic distances from human and mouse introns Jose Castresana Address: European Molecular Biology Laboratory (EMBL), Biocomputing Unit, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. Current address: Center for Genomic Regulation (CRG), Biocomputing Program, Dr Aiguader 80, 08003 Barcelona, Spain. E-mail: jose.castresana@crg.es Published: 14 May 2002 Received: 3 December 2001 Revised: 1 February 2002 Accepted: 27 March 2002 GenomeBiology 2002, 3(6):research0028.1–0028.7 The electronic version of this article is the complete one and can be found online at /2002/3/6/research/0028 ? 2002 Castresana, licensee BioMed Central Ltd (Print ISSN 1465-6906; Online ISSN 1465-6914) Abstract Background: Using genetic distances measured from exons, it has been observed that the mutation rate is not constant along mammalian chromosomes. Exons constitute only 1% of the human genome, however, and thus they cannot provide a complete picture of the mutational variation in the genome. Results: I calculated genetic distances between 504 human introns and their orthologous mouse counterparts from a set of 63 pairs of human and mouse genes scattered through the genome using a recently developed method that can extract reliably aligned regions from the introns in an objective manner. I found a significant correlation between the genetic distance measured in the conserved intron segments and the synonymous and nonsynonymous distances measured in the corresponding coding exons, indicating that genes with fast-evolving exons tend to have fast- evolving introns, and vice versa. Conclusions: These results indicate that introns, which extend over almost a quarter of the human genome, contain useful information for fully understanding the mutational dynamics of human and mouse genomes. This work also supports the idea that there is a mutational fo