Presented by: Chelsea Herron

Regulatory difference vs. phenotypic difference

Enhancers & promoters

Enhancers: regulate transcription

Promoters: regulate binding of RNA polymerase

Enhancers & Promoters Where are they located?

Conserved or Recently evolved?

Do they differ between species?

http://meatex.co.uk/product/pig-liver/http://hubpages.com/hub/How-To-Understand-Your-

Blood-Tests-Biochemistry

http://www.askjpc.org/wsco/wsc_showconference.php?id=520

Histones & Lysine H3K27ac

H3K4me3

Enhancers identified by H3K27ac

Promoters identified by H3K27ac & H3K4me3

http://www.rndsystems.com/product_detail_objectname_exactachip.aspx

Enhancers bound to H3K27ac are located away from the start codon region & are more apt to evolve while promoters bound to H3K27ac & H3K4me3 are located near the start codon region.

Concentration Levels

Alignment w/ Ancestral DNA

Location within DNA

Mapped active promoter & enhancer elements

Adult Somatic tissue

20 species of mammals

Met Criteria

I. Capture large fraction of mammalian phylogenetic tree

II. Profile major placental orders

III.Extend understanding of regulatory evolution of mammals w/ highly divergent phenotypes

Biological replicates ≥ 2

Exceptions: Sei Whale & Dolphin

Histone rich markers w/ biologically reproducible peaks

H3K27ac

H3K4me3

Chromatin immunoprecipitation

Verify if protein is localized to specific DNA sequence

ChIP-seq

Method to analyze protein interactions w/ DNA

Gel electrophoresis &

nanodrop spectrophotometer

Illumina genome analyzerhttp://www.bio.brandeis.edu/haberlab/jehsite/chIP.html

The majority of enhancers are not conserved Exception: regions coding for primary liver functions

Exaptation from Ancestral DNA sequence

http://www.telegraph.co.uk/news/uknews/crime/6781990/Bat-preservation-area-being-used-to-rob-people.html & http://www.lasgralariasfoundation.org/RLGvarious/slides/saturnid%20moth%202.html

https://www.flickr.com/photos/mikewiz/11809326866/in/photostream/

Exaptation vs. Adaptation

o Natural selection for current fxn.

o A feature that was notproduced by natural selection for current use

Promoter regions, located near TSS, are highly conserved compared to enhancer regions, located away from TSS, which evolve relatively quickly except for enhancers that regulate transcription of primary liver function.

Enhancers w/ H3K27ac location

Promoters w/ H3K27ac & H3K4me3 location

Enhancers evolve quickly through exaptation

Areas of highly conserved Enhancers

Primary liver functions

Areas of highly conserved Promoters

“Housekeeping” functions

From this knowledge researchers may further progress in the analysis of regulatory evolution & its effects

Villar, D., et al. (2015). Enhancer Evolution across 20 Mammalian Species. Cell 160, 554-566.

http://www.jeffkorhan.com/2011/08/ask-your-customers-the-tough-questions.html