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  Substantial Regional Variation in Substitution Rates in the Human Genome: Importance of GC Content, Gene Density, and Telomere-Specific Effects

Arndt, P. F., Hwa, T., & Petrov, D. A. (2005). Substantial Regional Variation in Substitution Rates in the Human Genome: Importance of GC Content, Gene Density, and Telomere-Specific Effects. Journal of Molecular Evolution: the Journal of the International Society of Molecular Evolution, 60(6), 748-763. doi:10.1007/s00239-004-0222-5.

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Genre: Journal Article
Alternative Title : J. Mol. Evol.

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 Creators:
Arndt, Peter F.1, Author           
Hwa, Terence, Author
Petrov, Dmitri A., Author
Affiliations:
1Evolutionary Genomics (Peter Arndt), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479638              

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Free keywords: Genome evolution - Nucleotide substitution - Genomic isochores - Short interspersed elements
 Abstract: This study presents the first global, 1-Mbp-level analysis of patterns of nucleotide substitutions along the human lineage. The study is based on the analysis of a large amount of repetitive elements deposited into the human genome since the mammalian radiation, yielding a number of results that would have been difficult to obtain using the more conventional comparative method of analysis. This analysis revealed substantial and consistent variability of rates of substitution, with the variability ranging up to twofold among different regions. The rates of substitutions of C or G nucleotides with A or T nucleotides vary much more sharply than the reverse rates, suggesting that much of that variation is due to differences in mutation rates rather than in the probabilities of fixation of C/G vs. A/T nucleotides across the genome. For all types of substitution we observe substantially more hotspots than coldspots, with hotspots showing substantial clustering over tens of Mbp’s. Our analysis revealed that GC-content of surrounding sequences is the best predictor of the rates of substitution. The pattern of substitution appears very different near telomeres compared to the rest of the genome and cannot be explained by the genome-wide correlations of the substitution rates with GC content or exon density. The telomere pattern of substitution is consistent with natural selection or biased gene conversion acting to increase the GC-content of the sequences that are within 10–15 Mbp away from the telomere.

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Language(s): eng - English
 Dates: 2005-07-012005-05-31
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: eDoc: 264899
DOI: 10.1007/s00239-004-0222-5
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Title: Journal of Molecular Evolution : the Journal of the International Society of Molecular Evolution
  Other : J. Mol. Evol.
Source Genre: Journal
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Publ. Info: New York : Springer Verlag
Pages: - Volume / Issue: 60 (6) Sequence Number: - Start / End Page: 748 - 763 Identifier: ISSN: 0022-2844
CoNE: https://pure.mpg.de/cone/journals/resource/954925415946