Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes

Sankar Subramanian; S Kumar

doi:10.1101/gr.1152803

Back

Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes

Journal article

Open access

Peer reviewed

Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes

Sankar Subramanian and S Kumar

Genome Research, Vol.13(5), pp.838-844

2003

DOI: https://doi.org/10.1101/gr.1152803

Files and links (2)

pdf

PDF - Published Version (Open Access)191.18 kBDownload View

Published VersionPDF - Published Version (Open Access)CC BY-NC V4.0, Open Access

url

https://doi.org/10.1101/gr.1152803View

Published Version

Abstract

mutation

genome

primate genomes

noncoding DNA

Point mutation rates in exons (synonymous sites) and noncoding (introns and intergenic) regions are generally assumed to be the same. However, comparative sequence analyses of synonymous substitutions in exons (81 genes) and that of long intergenic fragments (141.3 kbp) of human and chimpanzee genomes reveal a 30%-60% higher mutation rate in exons than in noncoding DNA. We propose a differential CpG content hypothesis to explain this fundamental, and seemingly unintuitive, pattern. We find that the increased exonic rate is the result of the relative overabundance of synonymous sites involved in CpG dinucleotides, as the evolutionary divergence in non-CpG sites is similar in noncoding DNA and synonymous sites of exons. Expectations and predictions of our hypothesis are confirmed in comparisons involving more distantly related species, including human-orangutan, human-baboon, and human-macaque. Our results suggest an underlying mechanism for higher mutation rate in GC-rich genomic regions, predict nonlinear accumulation of mutations in pseudogenes over time, and provide a possible explanation for the observed higher diversity of single nucleotide polymorphisms (SNPs) in the synonymous sites of exons compared to the noncoding regions.

Details

Title: Neutral substitutions occur at a faster rate in exons than in noncoding DNA in primate genomes
Authors: Sankar Subramanian (Author) - Arizona University, United States
S Kumar (Author) - Arizona University, United States
Publication details: Genome Research, Vol.13(5), pp.838-844
Publisher: Cold Spring Harbor Laboratory Press
Date published: 2003
DOI: 10.1101/gr.1152803
ISSN: 1088-9051
Copyright note: Copyright © 2003 The Authors. This article is distributed under a Creative Commons CC-BY-NC Licence (Attribution-NonCommercial 4.0 International Licence, http://creativecommons.org/licences/by-nc/4.0/)
Organisation Unit: School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99450336602621
Output Type: Journal article

Metrics

74 File views/ downloads

407 Record Views

101 Times Cited - Web of Science

See more details

InCites Highlights

These are selected metrics from InCites Benchmarking & Analytics tool, related to this output

Web Of Science research areas: Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity

UN Sustainable Development Goals (SDGs)

This output has contributed to the advancement of the following goals:

Source: InCites