Enhancer Evolution across 20 Mammalian Species

Villar, Diego; Berthelot, Camille; Aldridge, Sarah; Rayner, Tim; Lukk, Margus; Pignatelli, Miguel; Park, Thomas J.; Deaville, Robert; Erichsen, Jonathan Thor; Jasinska, Anna J.; Turner, James M. A.; Bertelsen, Mads F.; Murchison, Elizabeth P.; Flicek, Paul; Odom, Duncan T.

doi:10.1016/j.cell.2015.01.006

Cited by 724 publications

(1,054 citation statements)

References 71 publications

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“…Similarly, we tried to prevent the inclusion in the data set of maturation leftovers of previous genes. We discarded the monoexonic transcripts embedded into introns and expressed in the same orientation of the host genes without independent supporting evidence for transcriptional initiation (either overlap with FANTOM Cap analysis of gene expression [CAGE] tags) (The FANTOM Consortium and the RIKEN PMI and CLST [DGT] 2014) or expressed enhancers (Methods; Villar et al 2015).…”

Section: Resultsmentioning

confidence: 99%

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Improved definition of the mouse transcriptome via targeted RNA sequencing

et al. 2016

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Targeted RNA sequencing (CaptureSeq) uses oligonucleotide probes to capture RNAs for sequencing, providing enriched read coverage, accurate measurement of gene expression, and quantitative expression data. We applied CaptureSeq to refine transcript annotations in the current murine GRCm38 assembly. More than 23,000 regions corresponding to putative or annotated long noncoding RNAs (lncRNAs) and 154,281 known splicing junction sites were selected for targeted sequencing across five mouse tissues and three brain subregions. The results illustrate that the mouse transcriptome is considerably more complex than previously thought. We assemble more complete transcript isoforms than GENCODE, expand transcript boundaries, and connect interspersed islands of mapped reads. We describe a novel filtering pipeline that identifies previously unannotated but high-quality transcript isoforms. In this set, 911 GENCODE neighboring genes are condensed into 400 expanded gene models. Additionally, 594 GENCODE lncRNAs acquire an open reading frame (ORF) when their structure is extended with CaptureSeq. Finally, we validate our observations using current FANTOM and Mouse ENCODE resources.

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Section: Resultsmentioning

confidence: 99%

“…Transcripts whose transcription initiation did not match any permissive FANTOM CAGE peak (The FANTOM Consortium and the RIKEN PMI and CLST [DGT] 2014) within 100 bp distance and not sharing at least 80% reciprocal coverage with mouse enhancers (Villar et al 2015) were discarded.…”

Section: Splicing Maturation Degradation Product Filteringmentioning

confidence: 99%

Improved definition of the mouse transcriptome via targeted RNA sequencing

et al. 2016

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“…They comprised 1067 genes and 289 641 SNPs were found in our data within these genes. Pig enhancer regions were downloaded from Villar et al (2015). These consisted of regions enriched in H3K27 acetylation (32 979 regions, 1 290 312 SNPs) and H3K4 trimethylation (10 756 regions, 122 311 SNPs) along the pig genome.…”

Section: Snp Annotationmentioning

confidence: 99%

The ‘heritability’ of domestication and its functional partitioning in the pig

et al. 2016

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We propose to estimate the proportion of variance explained by regression on genome-wide markers (or genomic heritability) when wild/domestic status is considered the phenotype of interest. This approach differs from the standard Fst in that it can accommodate genetic similarity between individuals in a general form. We apply this strategy to complete genome data from 47 wild and domestic pigs from Asia and Europe. When we partitioned the total genomic variance into components associated to subsets of single nucleotide polymorphisms (SNPs) defined in terms of their annotation, we found that potentially deleterious non-synonymous mutations (9566 SNPs) explained as much genetic variance as the whole set of 25 million SNPs. This suggests that domestication may have affected protein sequence to a larger extent than regulatory or other kinds of mutations. A pathway-guided analysis revealed ovarian steroidogenesis and leptin signaling as highly relevant in domestication. The genomic regression approach proposed in this study revealed molecular processes not apparent through typical differentiation statistics. We propose that at least some of these processes are likely new discoveries because domestication is a dynamic process of genetic selection, which may not be completely characterized by a static metric like Fst. Nevertheless, and despite some particularly influential mutation types or pathways, our analyses tend to rule out a simplistic genetic basis for the domestication process: neither a single pathway nor a unique set of SNPs can explain the process as a whole.

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“…31 Yet, the use of the term, in a number of recent high-profile publications on evolution illustrates its lasting potency. [32][33][34][35] We feel that [Het-s] is an interesting example of exaptation in which the process can be understood at the molecular level and pinned down to a single point mutation. In addition, the [Het-s] case is characterized by the coincidence of loss-offunction and neofunctionalization (neofunctionalization here corresponds to acquisition of the incompatibility function which confers a benefit in restricting various forms of parasitism).…”

Section: Evolutionary Origin Of [Het-s] or How A Loss-of-function Mamentioning

confidence: 99%

As a toxin dies a prion comes to life: A tentative natural history of the [Het-s] prion

Daskalov

Saupe

2015

Prion

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A variety of signaling pathways, in particular with roles in cell fate and host defense, operate by a prion-like mechanism consisting in the formation of open-ended oligomeric signaling complexes termed signalosomes. This mechanism emerges as a novel paradigm in signal transduction. Among the proteins forming such signaling complexes are the Nod-like receptors (NLR), involved in innate immunity. It now appears that the [Het-s] fungal prion derives from such a cell-fate defining signaling system controlled by a fungal NLR. What was once considered as an isolated oddity turns out to be related to a conserved and widespread signaling mechanism. Herein, we recall the relation of the [Het-s] prion to the signal transduction pathway controlled by the NWD2 Nod-like receptor, leading to activation of the HET-S pore-forming cell death execution protein. We explicit an evolutionary scenario in which formation of the [Het-s] prion is the result of an exaptation process or how a loss-of-function mutation in a pore-forming cell death execution protein (HET-S) has given birth to a functional prion ([Het-s]).

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Enhancer Evolution across 20 Mammalian Species

Cited by 724 publications

References 71 publications

Improved definition of the mouse transcriptome via targeted RNA sequencing

Improved definition of the mouse transcriptome via targeted RNA sequencing

The ‘heritability’ of domestication and its functional partitioning in the pig

As a toxin dies a prion comes to life: A tentative natural history of the [Het-s] prion

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