29 mammalian genomes reveal novel exaptations of mobile elements for likely regulatory functions in the human genome.

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2012-01

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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.

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10.1371/journal.pone.0043128

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Lowe, Craig B, and David Haussler (2012). 29 mammalian genomes reveal novel exaptations of mobile elements for likely regulatory functions in the human genome. PloS one, 7(8). p. e43128. 10.1371/journal.pone.0043128 Retrieved from https://hdl.handle.net/10161/17409.

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Lowe

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 genes are regulated between species, or between different individuals within a species, and how this causes traits to differ.  All students in Craig's lab are exposed to an interdisciplinary environment; current lab members have backgrounds in mathematics, computer science, neuroscience, developmental biology, and genetics.  Each year Craig teaches one or two courses on rotating topics of: ancient DNA, ethical issues in genomics, and software development for genetic analyses.


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