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

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Date
2007-05
Authors
Lowe, Craig B
Bejerano, Gill
Haussler, David
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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.
Type
Journal article
Subject
Humans
Serine Endopeptidases
Cell Adhesion Molecules, Neuronal
Nerve Tissue Proteins
Extracellular Matrix Proteins
DNA Transposable Elements
Signal Transduction
Genes, Regulator
Multigene Family
Genes, Developmental
Selection, Genetic
Permalink
https://hdl.handle.net/10161/17404
Published Version (Please cite this version)
10.1073/pnas.0611223104
Publication Info
Lowe, Craig B; Bejerano, Gill; & Haussler, David (2007). Thousands of human mobile element fragments undergo strong purifying selection near developmental genes. Proceedings of the National Academy of Sciences of the United States of America, 104(19). pp. 8005-8010. 10.1073/pnas.0611223104. Retrieved from https://hdl.handle.net/10161/17404.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Lowe

Craig Lowe

Assistant Professor of Molecular Genetics and Microbiology
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