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Covariation in Frequencies of Substitution, Deletion, Transposition, and Recombination During Eutherian Evolution

Departments of ¹Biochemistry and Molecular Biology,² Computer Science and Engineering, ³Statistics, and⁴ Health Evaluation Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA; ⁵Center for Biomolecular Science and Engineering, ⁶Howard Hughes Medical Institute, University of California, Santa Cruz, California 95064, USA; ⁷European Bioinformatics Institute, Hinxton, Cambridge, England CB10 1SD, UK; ⁸The Institute for Systems Biology, Seattle, Washington 98103-8904, USA

Six measures of evolutionary change in the human genome were studied, three derived from the aligned human and mouse genomes in conjunction with the Mouse Genome Sequencing Consortium, consisting of (1) nucleotide substitution per fourfold degenerate site in coding regions, (2) nucleotide substitution per site in relics of transposable elements active only before the human–mouse speciation, and (3) the nonaligning fraction of human DNA that is nonrepetitive or in ancestral repeats; and three derived from human genome data alone, consisting of (4) SNP density, (5) frequency of insertion of transposable elements, and (6) rate of recombination. Features 1 and 2 are measures of nucleotide substitutions at two classes of "neutral" sites, whereas 4 is a measure of recent mutations. Feature 3 is a measure dominated by deletions in mouse, whereas 5 represents insertions in human. It was found that all six vary significantly in megabase-sized regions genome-wide, and many vary together. This indicates that some regions of a genome change slowly by all processes that alter DNA, and others change faster. Regional variation in all processes is correlated with, but not completely accounted for, by GC content in human and the difference between GC content in human and mouse. [Supplemental material is available online at www.genome.org and http://www.soe.ucsc.edu/research/compbio/covariation/.]

E-MAIL rch8{at}psu.edu; FAX (814) 863-7024.
E-MAIL haussler{at}cse.ucsc.edu; FAX (831) 459-4829.

Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.844103.

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