Characterization and potential functional significance of human-chimpanzee large INDEL variation
13 pages
English
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Characterization and potential functional significance of human-chimpanzee large INDEL variation

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13 pages
English

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Although humans and chimpanzees have accumulated significant differences in a number of phenotypic traits since diverging from a common ancestor about six million years ago, their genomes are more than 98.5% identical at protein-coding loci. This modest degree of nucleotide divergence is not sufficient to explain the extensive phenotypic differences between the two species. It has been hypothesized that the genetic basis of the phenotypic differences lies at the level of gene regulation and is associated with the extensive insertion and deletion (INDEL) variation between the two species. To test the hypothesis that large INDELs (80 to 12,000 bp) may have contributed significantly to differences in gene regulation between the two species, we categorized human-chimpanzee INDEL variation mapping in or around genes and determined whether this variation is significantly correlated with previously determined differences in gene expression. Results Extensive, large INDEL variation exists between the human and chimpanzee genomes. This variation is primarily attributable to retrotransposon insertions within the human lineage. There is a significant correlation between differences in gene expression and large human-chimpanzee INDEL variation mapping in genes or in proximity to them. Conclusions The results presented herein are consistent with the hypothesis that large INDELs, particularly those associated with retrotransposons, have played a significant role in human-chimpanzee regulatory evolution.

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Publié le 01 janvier 2011
Nombre de lectures 13
Langue English
Poids de l'ouvrage 1 Mo

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Polavarapu et al . Mobile DNA 2011, 2 :13 http://www.mobilednajournal.com/content/2/1/13
R E S E A R C H Open Access Characterization and potential functional significance of human-chimpanzee large INDEL variation Nalini Polavarapu 2 , Gaurav Arora 1 , Vinay K Mittal 1 and John F McDonald 1*
Abstract Background: Although humans and chimpanzees have accumulated significant differences in a number of phenotypic traits since diverging from a common ancestor about six million years ago, their genomes are more than 98.5% identical at protein-coding loci. This modest degree of nucleotide divergence is not sufficient to explain the extensive phenotypic differences between the two species. It has been hypothesized that the genetic basis of the phenotypic differences lies at the level of gene regulation and is associated with the extensive insertion and deletion (INDEL) variation between the two species. To test the hypothesis that large INDELs (80 to 12,000 bp) may have contributed significantly to differences in gene regulation between the two species, we categorized human-chimpanzee INDEL variation mapping in or around genes and determined whether this variation is significantly correlated with previously determined differences in gene expression. Results: Extensive, large INDEL variation exists between the human and chimpanzee genomes. This variation is primarily attributable to retrotransposon insertions within the human lineage. There is a significant correlation between differences in gene expression and large human-chimpanzee INDEL variation mapping in genes or in proximity to them. Conclusions: The results presented herein are consistent with the hypothesis that large INDELs, particularly those associated with retrotransposons, have played a significant role in human-chimpanzee regulatory evolution. Keywords: insertion and deletion, differential gene expression, retrotransposon, noninterspersed sequence, human insertion, short interspersed nuclear element
Background extensive insertion and deletion (INDEL) variation Although humans and chimpanzees have accumulated between the two species [3]. significant differences in a number of phenotypic traits A number of comparative genomic studies focused on since diverging from a common ancestor about six to specific chromosomal regions of humans and nonhuman eight million years ago, their genomes are more than primates that have been carried out have revealed that 98.5% identical at protein-coding loci [1]. Since this significant INDEL variation exists between these species modest degree of nucleotide divergence does not seem [4,5]. For example, in a comparison of human chromo-sufficient to explain the extensive phenotypic differences some 21 and the syntenic chimpanzee chromosome 22, that exist between the two species, it has been hypothe- as many as 68,000 INDELs were identified [6]. We have sized that the genetic basis of the differences lies at the shown previously that interspersed repeats, particularly level of gene regulation [2] and is associated with the retrotransposons (RTs), have contributed significantly to the INDEL variation between humans and chimpanzees [7]. Because RT sequences located in or near genes have the capacity to significantly alter patterns of gene 1 *GPeCaorokrrgerireasHpInoPsnteidttieuttnIecneso:titmuctegefnore@Bigoaetnegcihn.eederuing&Bioscience,SchoolofBiology, expression,ithaslongbeenrecognizedthartytehvesleeiloen-f Technology, 315 Ferst Drive NW, Atlanta, GA 30332, USA ments may be important factors in regulato o ut Full list of author information is available at the end of the article © 2011 Polavarapu et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.