RT Journal Article
SR Electronic
T1 Natural Selection has Shaped Coding and Non-coding Transcription in Primate CD4+ T-cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 083212
DO 10.1101/083212
A1 Charles G. Danko
A1 Zhong Wang
A1 Edward J. Rice
A1 Tinyi Chu
A1 Andre L. Martins
A1 Elia Tait Wojno
A1 John T. Lis
A1 Lee W. Kraus
A1 Adam Siepel
YR 2016
UL http://biorxiv.org/content/early/2016/11/12/083212.abstract
AB Transcriptional regulatory changes have been shown to contribute to phenotypic differences between species, but many questions remain about how gene expression evolves. Here we report the first comparative study of nascent transcription in primates. We used PRO-seq to map actively transcribing RNA polymerases in resting and activated CD4+ T-cells in multiple human, chimpanzee, and rhesus macaque individuals, with rodents as outgroups. This approach allowed us to directly measure active transcription separately from post-transcriptional processes. We observed general conservation in coding and non-coding transcription, punctuated by numerous differences between species, particularly at distal enhancers and non-coding RNAs. Transcription factor binding sites are a primary determinant of transcriptional differences between species. We found evidence for stabilizing selection on gene expression levels and adaptive substitutions associated with lineage-specific transcription. Finally, rates of evolutionary change are strongly correlated with long-range chromatin interactions. These observations clarify the role of primary transcription in regulatory evolution.