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New paper out in Nucleic Acids Research! We use Evolve & Resequence to measure purifying selection & insertion bias on an active TE in Drosophila simulans. Check out the “Publications” tab for more details.
The first postdoc preprint is available: “Catching a wave: on the suitability of traveling-wave solutions in epidemiological modeling”! We use diffusion-theory and individual-based models to figure out when exactly limited individual dispersal starts to affect disease dynamics, such that spatial structure needs to be considered. The preprint is available on bioRxiv. Check out the “Research” tab for more details.
New paper out in Science (including cool cover art)! “Deep cis-regulatory homology of the butterfly wing pattern ground plan” studies the evolution and role of cis-regulatory elements of a patterning gene in five different butterfly species. Fun cross-disciplinary collaboration with Anyi Mazo-Vargos, Robert Reed, and others. Check out this Twitter thread of Anyi for more details!
New paper out in eLife! “Fitness effects of CRISPR endonucleases in Drosophila melanogaster populations” sheds light on the (off-target) fitness effects of CRISPR/Cas9 and their potential implications on gene drives and beyond! Exciting work in collaboration with Jackson Champer, Philipp Messer, Andrew Clark, and many others. Check out the “Publications” section for more details.
New paper out in G3! Happy to announce that “A homing suppression gene drive with multiplexed gRNAs maintains high drive conversion efficiency and avoids functional resistance alleles” is out now in G3. Spearheaded by talented student Emily Yang, we introduce a suppression drive that avoids the formation of functional resistance alleles in experimental Drosophila populations. Check out the “Publications” section for more details.
hello world. The “Spatial Structure” project has officially begun. Funded by the Marie Skłodowska-Curie Actions programme, this project aims towards improved agent-based models of mosquito transmitted diseases. More detail about the “Spatial Structure” project can be found under “Research”.
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Published in G3, 2016
Benchmarking different NGS mapping algorithms on simulated and empirical Pool-Seq data.
Recommended citation: Kofler R, Langmüller AM, Nouhaud P, Otte KA, Schlötterer C. Suitability of Different Mapping Algorithms for Genome-Wide Polymorphism Scans with Pool-Seq Data. G3 (Bethesda). 2016 Nov 8;6(11):3507-3515. doi: 10.1534/g3.116.034488
Published in Genetics, 2019
How to distinguish between different fitness components in experimental evolution.
Recommended citation: Jingxian Liu, Jackson Champer, Anna Maria Langmüller, Chen Liu, Joan Chung, Riona Reeves, Anisha Luthra, Yoo Lim Lee, Andrew H Vaughn, Andrew G Clark, Philipp W Messer, Maximum Likelihood Estimation of Fitness Components in Experimental Evolution, Genetics, Volume 211, Issue 3, 1 March 2019, Pages 1005–1017, https://doi.org/10.1534/genetics.118.301893
Low concordance of short-term and long-term selection responses in experimental Drosophila populations
Published in Molecular Ecology, 2020
Long-term Evolve and Resequence studies are btter suited to investigate complex evolutionary processes.
Recommended citation: Langmüller, AM, Schlötterer, C. Low concordance of short-term and long-term selection responses in experimental Drosophila populations. Mol Ecol. 2020; 29: 3466– 3475. https://doi.org/10.1111/mec.15579.
Published in BMC Biology, 2020
The fitness costs of insecticide restistance mutations in the Ace gene differ between experimental Drosophila populations in hot and cold temperature regimes.
Recommended citation: Langmüller, A.M., Nolte, V., Galagedara, R. et al. Fitness effects for Ace insecticide resistance mutations are determined by ambient temperature. BMC Biol 18, 157 (2020). https://doi.org/10.1186/s12915-020-00882-5
Fine Mapping without Phenotyping: Identification of Selection Targets in Secondary Evolve and Resequence Experiments
Published in Genome Biology and Evolution, 2021
How promising are follow-up experiments to fine-map potential selection targets in Evolve and Resequence Experiments? A simulation study.
Recommended citation: Anna Maria Langmüller, Marlies Dolezal, Christian Schlötterer, Fine Mapping without Phenotyping: Identification of Selection Targets in Secondary Evolve and Resequence Experiments, Genome Biology and Evolution, Volume 13, Issue 8, August 2021, evab154, https://doi.org/10.1093/gbe/evab154
A homing suppression gene drive with multiplexed gRNAs maintains high drive conversion efficiency and avoids functional resistance alleles
Published in G3, 2023
Gene drives are engineered alleles that can bias inheritance in their favor, allowing them to spread throughout a population. They could potentially be used to modify or suppress pest populations, such as mosquitoes that spread diseases. CRISPR/Cas9 homing drives, which copy themselves by homology-directed repair in drive/wild-type heterozygotes, are a powerful form of gene drive, but they are vulnerable to resistance alleles that preserve the function of their target gene. Such resistance alleles can prevent successful population suppression. Here, we constructed a homing suppression drive in Drosophila melanogaster that utilized multiplexed gRNAs to inhibit the formation of functional resistance alleles in its female fertility target gene. The selected gRNA target sites were close together, preventing reduction in drive conversion efficiency. The construct reached a moderate equilibrium frequency in cage populations without apparent formation of resistance alleles. However, a moderate fitness cost prevented elimination of the cage population, showing the importance of using highly efficient drives in a suppression strategy, even if resistance can be addressed. Nevertheless, our results experimentally demonstrate the viability of the multiplexed gRNAs strategy in homing suppression gene drives.
Recommended citation: Yang E, Metzloff M, Langmüller AM, Xu X, Clark AG, Messer PW, Champer J. A homing suppression gene drive with multiplexed gRNAs maintains high drive conversion efficiency and avoids functional resistance alleles. G3 (Bethesda). 2022 May 30;12(6):jkac081. doi: 10.1093/g3journal/jkac081. PMID: 35394026; PMCID: PMC9157102.
Published in eLife, 2022
CRISPR/Cas9 provides a highly efficient and flexible genome editing technology with numerous potential applications ranging from gene therapy to population control. Some proposed applications involve the integration of CRISPR/Cas9 endonucleases into an organism’s genome, which raises questions about potentially harmful effects to the transgenic individuals. One example for which this is particularly relevant are CRISPR-based gene drives conceived for the genetic alteration of entire populations. The performance of such drives can strongly depend on fitness costs experienced by drive carriers, yet relatively little is known about the magnitude and causes of these costs. Here, we assess the fitness effects of genomic CRISPR/Cas9 expression in Drosophila melanogaster cage populations by tracking allele frequencies of four different transgenic constructs that allow us to disentangle direct fitness costs due to the integration, expression, and target-site activity of Cas9, from fitness costs due to potential off-target cleavage. Using a maximum likelihood framework, we find that a model with no direct fitness costs but moderate costs due to off-target effects fits our cage data best. Consistent with this, we do not observe fitness costs for a construct with Cas9HF1, a high-fidelity version of Cas9. We further demonstrate that using Cas9HF1 instead of standard Cas9 in a homing drive achieves similar drive conversion efficiency. These results suggest that gene drives should be designed with high-fidelity endonucleases and may have implications for other applications that involve genomic integration of CRISPR endonucleases.
Recommended citation: Langmüller AM, Champer J, Lapinska S, Xie L, Metzloff M, Champer SE, Liu J, Xu Y, Du J, Clark AG, Messer PW. Fitness effects of CRISPR endonucleases in Drosophila melanogaster populations. Elife. 2022 Sep 22;11:e71809. doi: 10.7554/eLife.71809.
Published in Science, 2022
Butterfly wing patterns derive from a deeply conserved developmental ground plan yet are diverse and evolve rapidly. It is poorly understood how gene regulatory architectures can accommodate both deep homology and adaptive change. To address this, we characterized the cis-regulatory evolution of the color pattern gene WntA in nymphalid butterflies. Comparative assay for transposase-accessible chromatin using sequencing (ATAC-seq) and in vivo deletions spanning 46 cis-regulatory elements across five species revealed deep homology of ground plan–determining sequences, except in monarch butterflies. Furthermore, noncoding deletions displayed both positive and negative regulatory effects that were often broad in nature. Our results provide little support for models predicting rapid enhancer turnover and suggest that deeply ancestral, multifunctional noncoding elements can underlie rapidly evolving trait systems.
Recommended citation: Mazo-Vargas A, Langmüller AM, Wilder A, Van der Burg KRL, Lewis JJ, Messer PW, Zhang L, Martin A, Reed RD. Science. 2022 Oct 20; 378:304-308. doi: 10.1126/science.abi9407
The genomic distribution of transposable elements is driven by spatially variable purifying selection
Published in Nucleic Acids Research, 2023
It is widely accepted that the genomic distribution of transposable elements (TEs) mainly reflects the outcome of purifying selection and insertion bias. Nevertheless, the relative importance of these two evolutionary forces could not be tested thoroughly. Here, we introduce an experimental system, which allows separating purifying selection from TE insertion bias. We used experimental evolution to study the TE insertion patterns in Drosophila simulans founder populations harboring 1040 insertions of an active P-element. After 10 generations at a large population size, we detected strong selection against P-element insertions. The exception were P-element insertions in genomic regions for which a strong insertion bias has been proposed. Because recurrent P-element insertions cannot explain this pattern, we conclude that purifying selection, with variable strength along the chromosomes, is the major determinant of the genomic distribution of P-elements. Genomic regions with relaxed purifying selection against P-element insertions exhibit normal levels of purifying selection against base substitutions. This suggests that different types of purifying selection operate on base substitutions and P-element insertions. Our results highlight the power of experimental evolution to understand basic evolutionary processes, which are difficult to infer from patterns of natural variation alone.
Recommended citation: Langmüller AM, Nolte V, Dolezal M, Schlötterer C. Nucleic Acids Research. 2023 Aug 10; gkad635. doi: 10.1093/nar/gkad635
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Undergraduate course, University 1, Department, 2014
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Workshop, University 1, Department, 2015
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