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Proc Natl Acad Sci U S A. 2007 May 8;104(19):8005-10. Epub 2007 Apr 26.

Thousands of human mobile element fragments undergo strong purifying selection near developmental genes.

Author information

1
Center for Biomolecular Science and Engineering, University of California, Santa Cruz, CA 95064, USA.

Abstract

At least 5% of the human genome predating the mammalian radiation is thought to have evolved under purifying selection, yet protein-coding and related untranslated exons occupy at most 2% of the genome. Thus, the majority of conserved and, by extension, functional sequence in the human genome seems to be nonexonic. Recent work has highlighted a handful of cases where mobile element insertions have resulted in the introduction of novel conserved nonexonic elements. Here, we present a genome-wide survey of 10,402 constrained nonexonic elements in the human genome that have all been deposited by characterized mobile elements. These repeat instances have been under strong purifying selection since at least the boreoeutherian ancestor (100 Mya). They are most often located in gene deserts and show a strong preference for residing closest to genes involved in development and transcription regulation. In particular, constrained nonexonic elements with clear repetitive origins are located near genes involved in cell adhesion, including all characterized cellular members of the reelin-signaling pathway. Overall, we find that mobile elements have contributed at least 5.5% of all constrained nonexonic elements unique to mammals, suggesting that mobile elements may have played a larger role than previously recognized in shaping and specializing the landscape of gene regulation during mammalian evolution.

PMID:
17463089
PMCID:
PMC1876562
DOI:
10.1073/pnas.0611223104
[Indexed for MEDLINE]
Free PMC Article

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