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

Lowe, Craig B

Haussler, David

Yu, Jr-Kai Sky

2018-09-13T14:41:28Z

2018-09-13T14:41:28Z

2012-01

2018-09-13T14:41:25Z

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.

PONE-D-12-04531

1932-6203

1932-6203

https://hdl.handle.net/10161/17409

eng

Public Library of Science (PLoS)

PloS one

10.1371/journal.pone.0043128

Animals

Mammals

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

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

Journal article

e43128

8

School of Medicine

Duke

Molecular Genetics and Microbiology

Basic Science Departments

Published

7