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Patterns of Insertions and Their Covariation With Substitutions in the Rat, Mouse, and Human Genomes

¹ Departments of Biochemistry and Molecular Biology, Center for Comparative Genomics and Bioinformatics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA ² Departments of Computer Science and Engineering, Center for Comparative Genomics and Bioinformatics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA ³ Department of Statistics, Center for Comparative Genomics and Bioinformatics, The Pennsylvania State University, University Park, Pennsylvania 16802, USA ⁴ The Institute for Systems Biology, Seattle, Washington 98103, USA ⁵ Center for Biomolecular Science and Engineering, University of California, Santa Cruz, California 95064, USA ⁶ Howard Hughes Medical Research Institute, The University of California at Santa Cruz, Santa Cruz, California 95964, USA

The rates at which human genomic DNA changes by neutral substitution and insertion of certain families of transposable elements covary in large, megabase-sized segments. We used the rat, mouse, and human genomic DNA sequences to examine these processes in more detail in comparisons over both shorter (rat–mouse) and longer (rodent–primate) times, and demonstrated the generality of the covariation. Different families of transposable elements show distinctive insertion preferences and patterns of variation with substitution rates. SINEs are more abundant in GC-rich DNA, but the regional GC preference for insertion (monitored in young SINEs) differs between rodents and humans. In contrast, insertions in the rodent genomes are predominantly LINEs, which prefer to insert into AT-rich DNA in all three mammals. The insertion frequency of repeats other than SINEs correlates strongly positively with the frequency of substitutions in all species. However, correlations with SINEs show the opposite effects. The correlations are explained only in part by the GC content, indicating that other factors also contribute to the inherent tendency of DNA segments to change over evolutionary time.

⁷ Corresponding author.
E-MAIL rch8{at}psu.edu; FAX (814) 863-7024.

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