Thousands of human mobile element fragments undergo strong purifying selection near developmental genes.
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 articleSubject
HumansSerine Endopeptidases
Cell Adhesion Molecules, Neuronal
Nerve Tissue Proteins
Extracellular Matrix Proteins
DNA Transposable Elements
Signal Transduction
Genes, Regulator
Multigene Family
Genes, Developmental
Selection, Genetic
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https://hdl.handle.net/10161/17404Published Version (Please cite this version)
10.1073/pnas.0611223104Publication 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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Craig Lowe
Assistant Professor of Molecular Genetics and Microbiology

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