29 mammalian genomes reveal novel exaptations of mobile elements for likely regulatory functions in the human genome.
Abstract
Recent research supports the view that changes in gene regulation, as opposed to changes
in the genes themselves, play a significant role in morphological evolution. Gene
regulation is largely dependent on transcription factor binding sites. Researchers
are now able to use the available 29 mammalian genomes to measure selective constraint
at the level of binding sites. This detailed map of constraint suggests that mammalian
genomes co-opt fragments of mobile elements to act as gene regulatory sequence on
a large scale. In the human genome we detect over 280,000 putative regulatory elements,
totaling approximately 7 Mb of sequence, that originated as mobile element insertions.
These putative regulatory regions are conserved non-exonic elements (CNEEs), which
show considerable cross-species constraint and signatures of continued negative selection
in humans, yet do not appear in a known mature transcript. These putative regulatory
elements were co-opted from SINE, LINE, LTR and DNA transposon insertions. We demonstrate
that at least 11%, and an estimated 20%, of gene regulatory sequence in the human
genome showing cross-species conservation was co-opted from mobile elements. The location
in the genome of CNEEs co-opted from mobile elements closely resembles that of CNEEs
in general, except in the centers of the largest gene deserts where recognizable co-option
events are relatively rare. We find that regions of certain mobile element insertions
are more likely to be held under purifying selection than others. In particular, we
show 6 examples where paralogous instances of an often co-opted mobile element region
define a sequence motif that closely matches a transcription factor's binding profile.
Type
Journal articleSubject
AnimalsMammals
Humans
Transcription Factors
5' Untranslated Regions
Models, Statistical
Sequence Alignment
Phylogeny
Binding Sites
Protein Binding
Gene Frequency
Genome
Genome, Human
Models, Genetic
Regulatory Elements, Transcriptional
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https://hdl.handle.net/10161/17409Published Version (Please cite this version)
10.1371/journal.pone.0043128Publication Info
Lowe, Craig B; & Haussler, David (2012). 29 mammalian genomes reveal novel exaptations of mobile elements for likely regulatory
functions in the human genome. PloS one, 7(8). pp. e43128. 10.1371/journal.pone.0043128. Retrieved from https://hdl.handle.net/10161/17409.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
Craig Lowe is an Assistant Professor in the Department of Molecular Genetics and Microbiology.
His research interests are in understanding how traits and characteristics of humans,
and other vertebrates, are encoded in their genomes. He is especially focused on
adaptations and disease susceptibilities that are unique to humans. To address these
questions, Craig uses both computational and experimental approaches. Craig's recent
research has been on differences in how gene

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