Genomewide Comparison of DNA Sequences between Humans and Chimpanzees

Ebersberger, Ingo; Metzler, Dirk; Schwarz, C.; Pääbo, Svante

doi:10.1086/340787

Cited by 311 publications

(253 citation statements)

References 26 publications

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“…In contrast, only 0.82% of ancestrally TpG or CpA show a change to CpG. This roughly estimated ∼sevenfold difference in forward and reverse mutation rates is in agreement with previous studies on disease mutations and comparative sequence analysis, which have shown CpG mutations to be 5-20 times more frequent than other types of point mutations (Batzer et al 1990;Yang et al 1996;Krawczak et al 1998;Giannelli et al 1999;Ebersberger et al 2002).…”

Section: Directionality Of the Cpg Mutationssupporting

confidence: 91%

Neutral Substitutions Occur at a Faster Rate in Exons Than in Noncoding DNA in Primate Genomes

Subramanian¹,

Kumar²

2003

Genome Res.

110

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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.

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Section: Directionality Of the Cpg Mutationssupporting

confidence: 91%

Neutral Substitutions Occur at a Faster Rate in Exons Than in Noncoding DNA in Primate Genomes

Subramanian¹,

Kumar²

2003

Genome Res.

110

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“…Similar trends have also been observed for HSA21q based on smaller comparisons with the chimpanzee genome 18 .…”

Section: Base Substitutionssupporting

confidence: 82%

DNA sequence and comparative analysis of chimpanzee chromosome 22

Watanabe

Fujiyama²,

Hattori³

et al. 2004

Nature

209

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Human–chimpanzee comparative genome research is essential for narrowing down genetic changes involved in the acquisition of unique human features, such as highly developed cognitive functions, bipedalism or the use of complex language. Here, we report the high-quality DNA sequence of 33.3 megabases of chimpanzee chromosome 22. By comparing the whole sequence with the human counterpart, chromosome 21, we found that 1.44% of the chromosome consists of single-base substitutions in addition to nearly 68,000 insertions or deletions. These differences are sufficient to generate changes in most of the proteins. Indeed, 83% of the 231 coding sequences, including functionally important genes, show differences at the amino acid sequence level. Furthermore, we demonstrate different expansion of particular subfamilies of retrotransposons between the lineages, suggesting different impacts of retrotranspositions on human and chimpanzee evolution. The genomic changes after speciation and their biological consequences seem more complex than originally hypothesized

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“…Sequence divergence between human and chimpanzee is relatively low for CYP3A43 and CYP3A7 (0.88 and 1%, respectively), as well as for CYP3A4 and CYP3A5 (0.86 and 0.66%) compared to the genome-wide average of 1.24%. 22 We identified a total of 224 polymorphic sites, including 13 biallelic and three multiallelic indels. Two hundred and four polymorphic sites were located in noncoding sequence and 20 in coding sequence, including eight synonymous (s) and 11 ns substitutions.…”

Section: Re-sequencing Survey Design and Resultsmentioning

confidence: 99%

Sequence diversity and haplotype structure at the human CYP3A cluster

et al. 2005

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The four members of the human CYP3A subfamily play important roles in the clearance of xenobiotics, hormones, and environmental compounds. Many SNPs at the CYP3A locus have been characterized, with several showing large allele frequency differences across populations. In addition to the effects of CYP3A SNPs on drug metabolism, recent studies have highlighted the potential for CYP3A variation in susceptibility to several common phenotypes, including hypertension and cancer. We previously showed that the CYP3A4 and CYP3A5 genes have a strong haplotype structure at varying frequencies across ethnic groups. Here, we extend our re-sequencing survey to the remaining CYP3A genes in the same cluster, CYP3A7 and CYP3A43. Our study identified a large number of SNPs in coding and conserved noncoding sequences, several of which are common. The combined data set allows us to investigate patterns of sequence variation and linkage disequilibrium at the entire CYP3A locus for use in future association studies.

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Genomewide Comparison of DNA Sequences between Humans and Chimpanzees

Cited by 311 publications

References 26 publications

Neutral Substitutions Occur at a Faster Rate in Exons Than in Noncoding DNA in Primate Genomes

Neutral Substitutions Occur at a Faster Rate in Exons Than in Noncoding DNA in Primate Genomes

DNA sequence and comparative analysis of chimpanzee chromosome 22

Sequence diversity and haplotype structure at the human CYP3A cluster

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