1000 Genomes Selection Browser 1.0: a genome browser dedicated to signatures of natural selection in modern humans

Pybus, Marc; Dall’Olio, Giovanni Marco; Luisi, Pierre; Uzkudun, Manu; Carreño-Torres, Angel; Pavlidis, Pavlos; Laayouni, Hafid; Bertranpetit, Jaume; Engelken, Johannes

doi:10.1093/nar/gkt1188

Cited by 142 publications

(175 citation statements)

References 59 publications

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“…3D; Supplemental Methods). The Fay and Wu's H values (Fay and Wu 2000;Pybus et al 2014) were not significantly different between Alu-containing exons with 3 ′ ss editing and the control exons (Supplemental Fig. S12).…”

Section: Wwwgenomeorgmentioning

confidence: 95%

RNA editing in nascent RNA affects pre-mRNA splicing

et al. 2018

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In eukaryotes, nascent RNA transcripts undergo an intricate series of RNA processing steps to achieve mRNA maturation. RNA editing and alternative splicing are two major RNA processing steps that can introduce significant modifications to the final gene products. By tackling these processes in isolation, recent studies have enabled substantial progress in understanding their global RNA targets and regulatory pathways. However, the interplay between individual steps of RNA processing, an essential aspect of gene regulation, remains poorly understood. By sequencing the RNA of different subcellular fractions, we examined the timing of adenosine-to-inosine (A-to-I) RNA editing and its impact on alternative splicing. We observed that >95% A-to-I RNA editing events occurred in the chromatin-associated RNA prior to polyadenylation. We report about 500 editing sites in the 3 ′ acceptor sequences that can alter splicing of the associated exons. These exons are highly conserved during evolution and reside in genes with important cellular function. Furthermore, we identified a second class of exons whose splicing is likely modulated by RNA secondary structures that are recognized by the RNA editing machinery. The genome-wide analyses, supported by experimental validations, revealed remarkable interplay between RNA editing and splicing and expanded the repertoire of functional RNA editing sites.

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Section: Wwwgenomeorgmentioning

confidence: 95%

RNA editing in nascent RNA affects pre-mRNA splicing

et al. 2018

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“…We compared our candidate regions to the top candidates of eight previous scans for selection, including iHS, F ST , XP-CLR, and HKA (Pybus et al 2014;Cagan et al 2016). Using the estimated time to the most recent common ancestor among Africans for each identified region/site, we found that our ELS scan identified significantly older events than other screens (Mann-Whitney U tests) ( Fig.…”

Section: Candidate Regions Of Positive Selection On the Human Lineagementioning

confidence: 99%

“…To compare our sweep screen with previous scans, we downloaded candidate regions from the 1000G positive selection database (Pybus et al 2014). Only candidates with a P-value lower than 0.001 were considered.…”

Section: Age Comparison With Other Scans For Selectionmentioning

confidence: 99%

“…Distributions of estimated ages of the modern human segregating derived variants with the highest frequency in putatively selected regions or the age of the derived variants at sites identified by various genome-wide scans. Our candidate regions are labeled as ELS, for Extended Lineage Sorting; other candidate regions are from Pybus et al (2014) and Cagan et al (2016). The color coding indicates the type of signal detected by each method.…”

Section: Overlap With Neandertal Introgressionmentioning

confidence: 99%

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Detecting ancient positive selection in humans using extended lineage sorting

et al. 2017

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Natural selection that affected modern humans early in their evolution has likely shaped some of the traits that set presentday humans apart from their closest extinct and living relatives. The ability to detect ancient natural selection in the human genome could provide insights into the molecular basis for these human-specific traits. Here, we introduce a method for detecting ancient selective sweeps by scanning for extended genomic regions where our closest extinct relatives, Neandertals and Denisovans, fall outside of the present-day human variation. Regions that are unusually long indicate the presence of lineages that reached fixation in the human population faster than expected under neutral evolution. Using simulations, we show that the method is able to detect ancient events of positive selection and that it can differentiate those from background selection. Applying our method to the 1000 Genomes data set, we find evidence for ancient selective sweeps favoring regulatory changes and present a list of genomic regions that are predicted to underlie positively selected human specific traits.[Supplemental material is available for this article.]Modern humans differ from their closest extinct relatives, Neandertals, in several aspects, including skeletal and skull morphology (Weaver 2009), and may also differ in other traits that are not preserved in the archeological record (Varki et al. 2008;Laland et al. 2010). Natural selection may have played a role in fixing these traits on the modern human lineage. However, the selection events driving the fixation would have been restricted to a specific timeframe, extending from the split between archaic and modern humans ca. 650,000 yr ago to the split of modern human populations from each other around 100,000 yr ago . While methods exist that can be used to scan the genome for the remnants of past or ongoing positive selection (Nielsen et al. 2007; Pybus and Shapiro 2009), current methods have limited power to detect positive selection on the human lineage that acted during this older timeframe (see Sabeti et al. 2006 for a review on detection methods and their timeframes): an unusually high ratio of functional changes to nonfunctional changes, such as the d N /d S test, requires millions of years and often multiple events of selection to generate detectable signals (Kryazhimskiy and Plotkin 2008), while unusual patterns of genetic diversity between individuals and populations (e.g., extended homozygosity, Tajima's D, F ST ) are most powerful during the selective sweep or shortly after (Sabeti et al. 2006;Oleksyk et al. 2010). A favorable substitution is not expected to leave a mark on linked neutral variation beyond 250,000 yr in humans (Przeworski 2002(Przeworski , 2003.The genome sequencing of archaic humans (Neandertals and Denisovans) to high coverage (Meyer et al. 2012;Prüfer et al. 2014) has spawned new methods to investigate the genetic basis of modern human traits that are not shared by the archaics (Pääbo 2014). One method, called 3P-CLR, models allele ...

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“…In 2000 the Human Genome Project equenced the first whole human genome, at a cost over USD$2 billion (Davies 2010). In 2012 the 1000 genomes project released their phase 1 sequencing data (Pybus et al 2014), documenting genetic variation in 1,000+ individuals from 25 populations from around the globe (The 1000 Genomes Project Consortium 2012). Genome sequencing costs continues to drop, and the USD$1,000 whole sequence genome is now available (Hayden 2014).…”

Section: Genome+mentioning

confidence: 99%

Genetic GIScience: Toward a Place-Based Synthesis of the Genome, Exposome, and Behavome

Jacquez¹,

Sabel²,

Chen³

2015

Annals of the Association of American Geographers

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The exposome, defined as the totality of an individual’s exposures over the life course, is a seminal concept in the environmental health sciences. Although inherently geographic, the exposome as yet is unfamiliar to many geographers. This article proposes a place-based synthesis, genetic geographic information science (Genetic GISc) that is founded on the exposome, genome+ and behavome. It provides an improved understanding of human health in relation to biology (the genome+), environmental exposures (the exposome), and their social, societal and behavioral determinants (the behavome). Genetic GISc poses three key needs: First, a mathematical foundation for emergent theory; Second, process-based models that bridge biological and geographic scales; Third, biologically plausible estimates of space-time disease lags. Compartmental models are a possible solution; this article develops two models using pancreatic cancer as an exemplar. The first models carcinogenesis based on the cascade of mutations and cellular changes that lead to metastatic cancer. The second models cancer stages by diagnostic criteria. These provide empirical estimates of the distribution of latencies in cellular states and disease stages, and maps of the burden of yet to be diagnosed disease. This approach links our emerging knowledge of genomics to cancer progression at the cellular level, to individuals and their cancer stage at diagnosis, to geographic distributions of cancer in extant populations. These methodological developments and exemplar provide the basis for a new synthesis in health geography: genetic geographic information science.

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1000 Genomes Selection Browser 1.0: a genome browser dedicated to signatures of natural selection in modern humans

Cited by 142 publications

References 59 publications

RNA editing in nascent RNA affects pre-mRNA splicing

RNA editing in nascent RNA affects pre-mRNA splicing

Detecting ancient positive selection in humans using extended lineage sorting

Genetic GIScience: Toward a Place-Based Synthesis of the Genome, Exposome, and Behavome

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