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Open Access Research article

Weak preservation of local neutral substitution rates across mammalian genomes

Hideo Imamura123, John E Karro4 and Jeffrey H Chuang1*

Author Affiliations

1 Boston College, Department of Biology, Chestnut Hill, MA, 02467 USA

2 Instituut voor Tropische Geneeskunde, B-2000 Antwerpen, Belgium

3 The Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK

4 Miami University of Ohio, Department of Computer Science & Systems Analysis and Department of Microbiology, Oxford, OH, 45056 USA

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BMC Evolutionary Biology 2009, 9:89  doi:10.1186/1471-2148-9-89

Published: 5 May 2009

Abstract

Background

The rate at which neutral (non-functional) bases undergo substitution is highly dependent on their location within a genome. However, it is not clear how fast these location-dependent rates change, or to what extent the substitution rate patterns are conserved between lineages. To address this question, which is critical not only for understanding the substitution process but also for evaluating phylogenetic footprinting algorithms, we examine ancestral repeats: a predominantly neutral dataset with a significantly higher genomic density than other datasets commonly used to study substitution rate variation. Using this repeat data, we measure the extent to which orthologous ancestral repeat sequences exhibit similar substitution patterns in separate mammalian lineages, allowing us to ascertain how well local substitution rates have been preserved across species.

Results

We calculated substitution rates for each ancestral repeat in each of three independent mammalian lineages (primate – from human/macaque alignments, rodent – from mouse/rat alignments, and laurasiatheria – from dog/cow alignments). We then measured the correlation of local substitution rates among these lineages. Overall we found the correlations between lineages to be statistically significant, but too weak to have much predictive power (r2 <5%). These correlations were found to be primarily driven by regional effects at the scale of several hundred kb or larger. A few repeat classes (e.g. 7SK, Charlie8, and MER121) also exhibited stronger conservation of rate patterns, likely due to the effect of repeat-specific purifying selection. These classes should be excluded when estimating local neutral substitution rates.

Conclusion

Although local neutral substitution rates have some correlations among mammalian species, these correlations have little predictive power on the scale of individual repeats. This indicates that local substitution rates have changed significantly among the lineages we have studied, and are likely to have changed even more for more diverged lineages. The correlations that do persist are too weak to be responsible for many of the highly conserved elements found by phylogenetic footprinting algorithms, leading us to conclude that such elements must be conserved due to selective forces.