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Distinct Changes of Genomic Biases in Nucleotide Substitution at the Time of Mammalian Radiation
 

Summary: Distinct Changes of Genomic Biases in Nucleotide Substitution at the Time
of Mammalian Radiation
Peter F. Arndt,* Dmitri A. Petrov,à and Terence Hwa*
*Physics Department and Center for Theoretical Biological Physics, University of California at San Diego; Institute for
Theoretical Physics, Cologne University, Cologne, Germany; and àDepartment of Biological Sciences, Stanford University
Differences in the regional substitution patterns in the human genome created patterns of large-scale variation of base
composition known as genomic isochores. To gain insight into the origin of the genomic isochores, we develop
a maximum-likelihood approach to determine the history of substitution patterns in the human genome. This approach
utilizes the vast amount of repetitive sequence deposited in the human genome over the past approximately 250 Myr.
Using this approach, we estimate the frequencies of seven types of substitutions: the four transversions, two transitions,
and the methyl-assisted transition of cytosine in CpG. Comparing substitutional patterns in repetitive elements of various
ages, we reconstruct the history of the base-substitutional process in the different isochores for the past 250 Myr. At
around 90 MYA (around the time of the mammalian radiation), we find an abrupt fourfold to eightfold increase of the
cytosine transition rate in CpG pairs compared with that of the reptilian ancestor. Further analysis of nucleotide
substitutions in regions with different GC content reveals concurrent changes in the substitutional patterns. Although the
substitutional pattern was dependent on the regional GC content in such ways that it preserved the regional GC content
before the mammalian radiation, it lost this dependence afterward. The substitutional pattern changed from an isochore-
preserving to an isochore-degrading one. We conclude that isochores have been established before the radiation of the
eutherian mammals and have been subject to the process of homogenization since then.
Introduction

  

Source: Arndt, Peter - Max-Planck-Institut für molekulare Genetik
Petrov, Dmitri - Department of Biology, Stanford University
Spang, Rainer - Computational Molecular Biology Group, Max-Planck-Institut für molekulare Genetik

 

Collections: Biology and Medicine; Biotechnology; Computer Technologies and Information Sciences; Physics