Simulation of Genes and Genomes Forward in Time

Carvajal-Rodríguez, Antonio

doi:10.2174/138920210790218007

Cited by 44 publications

(58 citation statements)

References 30 publications

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“…While this is computationally more intensive than coalescent approaches, it remains a prerequisite for modeling scenarios with multiple linked polymorphisms of different selective effects. Forward simulations have a long-standing tradition in population genetics and many programs have been developed, see [1][2][3]. For any such program, there is typically a trade-off between efficiency, flexibility, and ease of use.…”

Section: Overviewmentioning

confidence: 99%

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SLiM: Simulating Evolution with Selection and Linkage

2013

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SLiM is an efficient forward population genetic simulation designed for studying the effects of linkage and selection on a chromosome-wide scale. The program can incorporate complex scenarios of demography and population substructure, various models for selection and dominance of new mutations, arbitrary gene structure, and user-defined recombination maps. RECENT studies suggest that linkage effects such as genetic draft and background selection can profoundly alter the patterns of genetic variation in many species (Sella et al. 2009; Lohmueller et al. 2011; Weissman and Barton 2012; Messer and Petrov 2013). Understanding the potential impact of these linkage effects on population genetic methods requires efficient forward simulations that can model the evolution of whole chromosomes with realistic gene structure.Forward simulations have a long-standing tradition in population genetics and many programs have been developed (Carvajal-Rodriguez 2010;Hoban et al. 2011). For any such program, there is typically a trade-off between efficiency and flexibility. Simulations based on combined forward-backward approaches, such as MSMS (Ewing and Hermisson 2010), can be very fast but remain limited to scenarios with only a single selected locus. Current programs that can model scenarios with multiple linked selected polymorphisms, such as FRE-GENE (Chadeau-Hyam et al. 2008), GENOMEPOP (CarvajalRodriguez 2008), simuPOP (Peng and Kimmel, 2005), forwsim (Padhukasahasram et al. 2008), or SFS_CODE (Hernandez 2008, either lack the ability to model realistic gene structure or are not efficient enough to allow for simulations on the scale of a whole chromosome in reasonably large populations.Here I present SLiM, a population genetic simulation targeted at bridging the gap between efficiency and flexibility for the simulation of linkage and selection on a chromosomewide scale. The program can incorporate complex scenarios of demography and population substructure, various models for selection and dominance, realistic gene structure, and user-defined recombination maps. Special emphasis was further placed on the ability to model and track individual selective sweeps-both complete and partial. While retaining all capabilities of a forward simulation, SLiM utilizes sophisticated algorithms and optimized data structures that enable simulations in reasonably large populations. All these features are implemented in an easy-to-use C++ command line program. The source code is freely available under the GNU General Public License and can be downloaded from http://www.stanford.edu/~messer/software.SLiM simulates the evolution of diploid genomes in a population of hermaphrodites under an extended WrightFisher model with selection ( Figure 1A). In each generation, a new set of offspring is created, descending from the individuals in the previous generation. The probability of becoming a parent is proportional to an individual's fitness, which is determined by the selection and dominance effects of the mutations present in its diplo...

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Section: Overviewmentioning

confidence: 99%

“…Forward simulations have a long-standing tradition in population genetics and many programs have been developed (Carvajal-Rodriguez 2010;Hoban et al 2011). For any such program, there is typically a trade-off between efficiency and flexibility.…”

mentioning

confidence: 99%

SLiM: Simulating Evolution with Selection and Linkage

2013

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“…This kind of work led in 2000 to the approval of Zyvox, the first entirely new antibiotic to reach the market in 35 years. [117][118][119][120][121][122][123][124][125][126][127][128] Genomics and sequencing of human genome The sequencing of the human genome, completed just three years ago, also has given scientists an incredibly rich "parts list" with which to better understand why and how disease happens. In the foreseeable future not only will every human gene will be identified, but the factors controlling their expression will also be known.…”

Section: Antisense Technologymentioning

confidence: 99%

Medical Biotechnology: Problems and Prospects in Bangladesh

Mizan

2013

J Enam Med Col

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“…Detailed reviews on the subject are available elsewhere (e.g., see Carvajal-Rodgríguez, 2008;Kim & Wiehe, 2008;Liu et al, 2008;Carvajal-Rodríguez, 2010). It is useful to provide a general overview of these programs to properly appreciate the types of problems that can be addressed with such simulations.…”

Section: Forward-time Population Genetic Numerical Simulationsmentioning

confidence: 99%

“…Fitness is assigned to individuals before mating, and parents to reproduce are chosen with probabilities proportional to their fitness. Readers are encouraged to examine these and other programs to determine which is best suited for particular applications (Carvajal-Rodgríguez, 2008;Kim & Wiehe, 2008;Liu et al, 2008;Carvajal-Rodríguez, 2010). Among these forward-time simulations, Mendel appears to be unique in that it is the first comprehensive (and hence most biologically realistic) population genetics numerical simulator.…”

Section: Avidamentioning

confidence: 99%