Unknown,Transcriptomics,Genomics,Proteomics

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Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection [DGE-seq]


ABSTRACT: The human genome shares a remarkable amount of genomic sequence with our closest living primate relatives. Researchers have long sought to understand what regions of the genome are responsible for unique species-specific traits. Previous studies have shown that many genes are differentially expressed between species, but the regulatory elements contributing to these differences are largely unknown. Here we report a genome-wide comparison of active gene regulatory elements in human, chimpanzee, and macaque, and we identify hundreds of regulatory elements that have been gained or lost in the human or chimpanzee genomes since their evolutionary divergence. These elements contain evidence of natural selection and correlate with species-specific changes in gene expression. Polymorphic DNA bases in transcription factor motifs that we found in these regulatory elements may be responsible for the varied biological functions across species. This study directly links phenotypic and transcriptional differences between species with changes in chromatin structure. DGE-seq

ORGANISM(S): Homo sapiens

SUBMITTER: Yoichiro Shibata 

PROVIDER: E-GEOD-54906 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection.

Shibata Yoichiro Y   Sheffield Nathan C NC   Fedrigo Olivier O   Babbitt Courtney C CC   Wortham Matthew M   Tewari Alok K AK   London Darin D   Song Lingyun L   Lee Bum-Kyu BK   Iyer Vishwanath R VR   Parker Stephen C J SC   Margulies Elliott H EH   Wray Gregory A GA   Furey Terrence S TS   Crawford Gregory E GE  

PLoS genetics 20120628 6


Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regu  ...[more]

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