scrm: efficiently simulating long sequences using the approximated coalescent with recombination

Staab, Paul; Zhu, Sha; Metzler, Dirk; Lunter, Gerton

doi:10.1093/bioinformatics/btu861

Cited by 122 publications

(151 citation statements)

References 9 publications

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“…The final model, as shown in Figure 5, was then also simulated using the SCRM simulator 49 , and we verified that Rarecoal was able to infer the true parameters after simulation.…”

Section: Rarecoal Analysismentioning

confidence: 62%

Na-Dene populations descend from the Paleo-Eskimo migration into America

Flegontov

Altınışık

Changmai

et al. 2016

Preprint

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Prehistory of Native Americans of the Na-Dene language family remains controversial. Genetic continuity of Paleo-Eskimos (Saqqaq and Dorset cultures) and Na-Dene was proposed under the three-wave model of America's settlement; however, recent studies have produced conflicting results. Here, we performed reconstruction and dating of Na-Dene population history, using genome sequencing data and a coalescent method relying on rare alleles (Rarecoal). We also applied model-free approaches for analysis of rare allele and autosomal haplotype sharing. All methods detected Central and West Siberian ancestry exclusively in a fraction of modern day Na-Dene individuals, but not in other Native Americans. Our results are consistent with gene flow from Paleo-Eskimos into the First American ancestors of Na-Dene, and a later less extensive bidirectional admixture between Na-Dene and Neo-Eskimos. The dated gene flow from Siberia to Na-Dene is in agreement with the Dene-Yeniseian language macrofamily proposal and with the succession of archaeological cultures in Siberia.

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“…The final model, as shown in Figure 5, was then also simulated using the SCRM simulator 49 , and we verified that Rarecoal was able to infer the true parameters after simulation.…”

Section: Rarecoal Analysismentioning

confidence: 62%

Na-Dene populations descend from the Paleo-Eskimo migration into America

Flegontov

Altınışık

Changmai

et al. 2016

Preprint

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“…Neutral simulations were generated with the coalescent simulator scrm (Staab et al 2014) and give a good match to our observed data when plotting derived allele frequency in modern humans against the proportion of derived alleles in the outgroup (Supplemental Fig. S8).…”

Section: Simulationsmentioning

confidence: 99%

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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“…For each model for IRh, 1-Gb length DNA sequences of 52 individuals were simulated using the coalescent-based algorithm SMC (McVean and Cardin 2005;Marjoram and Wall 2006) implemented in the scrm software package (Staab et al 2015). Similarly, for each model for CRh, 1-Gb length DNA sequences of three individuals were simulated.…”

Section: Comparison Of Demographic Histories and Testing For Fit Agaimentioning

confidence: 99%

“…To investigate our ability to infer recent population size growth/recovery, we simulated 200 DNA sequence samples using the scrm software package (Staab et al 2015). The stairway plot estimation based on 75 high-coverage IRh is assumed to be the true demographic model.…”

Section: Simulation Study Assuming a Population Size Recoverymentioning

confidence: 99%

The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences

et al. 2016

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Rhesus macaques (Macaca mulatta) are the most widely used nonhuman primate in biomedical research, have the largest natural geographic distribution of any nonhuman primate, and have been the focus of much evolutionary and behavioral investigation. Consequently, rhesus macaques are one of the most thoroughly studied nonhuman primate species. However, little is known about genome-wide genetic variation in this species. A detailed understanding of extant genomic variation among rhesus macaques has implications for the use of this species as a model for studies of human health and disease, as well as for evolutionary population genomics. Whole-genome sequencing analysis of 133 rhesus macaques revealed more than 43.7 million single-nucleotide variants, including thousands predicted to alter protein sequences, transcript splicing, and transcription factor binding sites. Rhesus macaques exhibit 2.5-fold higher overall nucleotide diversity and slightly elevated putative functional variation compared with humans. This functional variation in macaques provides opportunities for analyses of coding and noncoding variation, and its cellular consequences. Despite modestly higher levels of nonsynonymous variation in the macaques, the estimated distribution of fitness effects and the ratio of nonsynonymous to synonymous variants suggest that purifying selection has had stronger effects in rhesus macaques than in humans. Demographic reconstructions indicate this species has experienced a consistently large but fluctuating population size. Overall, the results presented here provide new insights into the population genomics of nonhuman primates and expand genomic information directly relevant to primate models of human disease.

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scrm: efficiently simulating long sequences using the approximated coalescent with recombination

Cited by 122 publications

References 9 publications

Na-Dene populations descend from the Paleo-Eskimo migration into America

Na-Dene populations descend from the Paleo-Eskimo migration into America

Detecting ancient positive selection in humans using extended lineage sorting

The population genomics of rhesus macaques (Macaca mulatta) based on whole-genome sequences

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