DOCSLIB.ORG

An Epigenetic Analysis of the Robustness of the Honeybee (Apis Mellifera) Queen Developmental Pathway

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
An Epigenetic Analysis of the Robustness of the Honeybee (Apis Mellifera) Queen Developmental Pathway Molecular Ecology (2017) 26, 1598–1607 doi: 10.1111/mec.13990 Making a queen: an epigenetic analysis of the robustness of the honeybee (Apis mellifera) queen developmental pathway XU JIANG HE,* LIN BIN ZHOU,* QI ZHONG PAN,* ANDREW B. BARRON,† WEI YU YAN* and ZHI JIANG ZENG* *Honeybee Research Institute, Jiangxi Agricultural University, Nanchang, Jiangxi 330045, China, †Department of Biological Sciences, Macquarie University, North Ryde, NSW 2109, Australia Abstract Specialized castes are considered a key reason for the evolutionary and ecological suc- cess of the social insect lifestyle. The most essential caste distinction is between the fertile queen and the sterile workers. Honeybee (Apis mellifera) workers and queens are not genetically distinct, rather these different phenotypes are the result of epige- netically regulated divergent developmental pathways. This is an important phe- nomenon in understanding the evolution of social insect societies. Here, we studied the genomic regulation of the worker and queen developmental pathways, and the robustness of the pathways by transplanting eggs or young larvae to queen cells. Queens could be successfully reared from worker larvae transplanted up to 3 days age, but queens reared from older worker larvae had decreased queen body size and weight compared with queens from transplanted eggs. Gene expression analysis showed that queens raised from worker larvae differed from queens raised from eggs in the expression of genes involved in the immune system, caste differentiation, body development and longevity. DNA methylation levels were also higher in 3-day-old queen larvae raised from worker larvae compared with that raised from transplanted eggs identifying a possible mechanism stabilizing the two developmental paths. We propose that environmental (nutrition and space) changes induced by the commercial rearing practice result in a suboptimal queen phenotype via epigenetic processes, which may potentially contribute to the evolution of queen–worker dimorphism. This also has potentially contributed to the global increase in honeybee colony failure rates. Keywords: DNA methylation, epigenetic analysis, gene expression, honeybee, immunity, queen Received 7 March 2016; revision received 12 December 2016; accepted 19 December 2016 (Queller & Strassmann 1998; Linksvayer & Wade 2005; Introduction Foster et al. 2006). Oster and Wilson have particularly The evolution of cooperation, cooperative living and emphasized the importance of caste in the evolution of animal societies has been an enduring subject of fasci- social insect societies (Oster & Wilson 1978). Different nation for evolutionary biologists (Wilson 1975). Key castes within the society specialize on different func- insights into the processes of social evolution have tions. This specialization promotes efficiencies, which come from studies of the advanced social insects (Eilson provides a key selective advantage to social living. 1971; Andersson 1984; Robinson 1999). These have Oster & Wilson (1978) argue castes are one key reason shaped our understanding of the genetic and ecological for the ecological success of the social insect lifestyle. factors that can promote the evolution of sociality Queens and workers are the defining caste distinction for the social insects. Queens have multiple morpholog- ical and behavioural specializations for extreme fecun- Correspondence: Zhi Jiang Zeng, Fax: +86 791 83828176; dity, whereas workers show a similar degree of E-mail: [email protected] © 2016 John Wiley & Sons Ltd EPIGENETIC CHANGES IN HONEYBEE QUEEN REARING 1599 specialization for social roles supporting the queens’ and space) changes induced by the commercial rearing reproduction, and in many social insects workers are practice may potentially affect queen development via sterile. This is the case for honeybees (Apis mellifera). A epigenetic processes. Here, we explored the conse- typical colony contains a single reproductive queen sup- quence of age of transplant from worker cells to queen ported by up to 50 000 sterile workers (Winston 1991). cells on DNA methylation, gene expression and queen Studies of the bee have shown how the distinction morphology. We found that the domestic rearing prac- between queens and workers is not genetic: rather these tice altered queen morphology and induced epigenetic two phenotypes are the outcome of different develop- changes in developing queens, which supports our mental pathways (Nijhout 2003; Linksvayer et al. 2011). hypothesis. Both queens and workers develop from fertilized eggs, but differences in nutrition and the amount of Materials and methods food given to young larvae trigger different epigeneti- cally regulated developmental pathways (Kucharski Three European honeybee colonies (Apis mellifera) each et al. 2008; Maleszka 2014; Maleszka et al. 2014). with a single drone inseminated queen (SDI) were used Kucharski et al. (2008) reported that nutritional differ- throughout this study. These colonies were maintained ences between queen and worker at their larval stage at the Honeybee Research Institute, Jiangxi Agricultural control their development via DNA methylation. Shi University, Nanchang, China (28.46 uN, 115.49 uE), et al. (2011) showed that the amount of space in which according to the standard beekeeping techniques. a larva can develop alters the DNA methylation level of the larval genome and contributes to the process of Queen-rearing methods caste differentiation. Changes in gene regulation caused by these epigenetic mechanisms then establish diver- Queens were restricted for 6 h to a plastic honeybee gent developmental paths (Simola et al. 2013), involving frame developed by Pan et al. (2013) for laying. The particularly genes involved in signal transduction, frame is designed such that the plastic base of this gland development and carbohydrate metabolism frame with eggs or larvae can be transferred to plastic (Woodard et al. 2011). queen cells directly (Pan et al. 2013). Eggs that queen Since the 19th century in commercial beekeeping, it laid in worker cells were transplanted into queen cells has been a standard practice to raise queens by trans- for rearing new queens when eggs were less than 6 h planting eggs or young larvae into artificial queen cells, old (QWE). For the other experimental groups, day 1, which triggers workers to raise a queen (Doolittle 1888; day 2 and day 3 worker larvae were transplanted into Buchler€ et al. 2013). Within the commercial queen-rear- queen cells for rearing QWL1, QWL2 and QWL3, ing practice, there is variation in the age at which eggs respectively. Queen cells with worker eggs or larvae or worker larvae are transplanted to queen cells to be were returned into their natal colonies (the SDI colo- raised as queens. It is not clear how well the honeybees’ nies) for queen rearing. developmental processes are able to tolerate this kind For the morphological measurements, new emerging of intervention. Woyke (1971) reported that rearing queens were collected and their weight measured using queens from young worker larvae resulted in decreased an analytical balance (FA3204B; Shanghai Precision Sci- body size, a smaller spermatheca and fewer ovarioles. entific Instrument Co., Ltd.). Their thorax width and Rangel et al. (2012) reported that colonies from queens length were measured with a zoom stereo microscope reared from older worker larvae had significantly lower system (Panasonic Co., Ltd.) according to the manufac- production of worker comb, drone comb and stored turer’s instructions. food compared with colonies from queens reared from For epigenetic analysis, we sampled 3-day-old larvae young worker larvae. In fact, concern over the long- from QWE, QWL1 and QWL2, respectively, from their term consequences of commercial queen rearing for bee queen cell. The fourth group QWL3 sampled 3-day-old stocks is not new. In 1923, Rudolf Steiner predicted that worker larvae directly from worker cells. Each sample honeybees would become extinct within 100 years as a group collected three larvae and there were three bio- consequence of commercial queen rearing progressively logical replicates, each from different colonies, for each weakening bee stocks (Thomas 1998). In the current group. We weighed each larva from these four treat- environment of increased honeybee colony failure rates, ment groups with an analytical balance. All samples mass deaths of colonies and declining honeybee stocks, were immediately flash-frozen in liquid nitrogen. The there is a great deal of concern as to whether a decline DNA and RNA from each sample were both extracted in queen bee quality might be a factor in these prob- for further DNA methylation and RNA sequencing lems (van Engelsdorp et al. 2010; Delaney et al. 2011). analysis. DNA and RNA were extracted from the same Therefore, we hypothesize that environmental (nutrition samples. © 2016 John Wiley & Sons Ltd 1600 X. J. HE ET AL. < RNA-Seq analysis KEGG protein database by BLAST (E-value 1e-5) and used KOBAS 2.0 software to test the statistical enrichment Total RNA was extracted from larvae according to the of differential expression genes in KEGG pathways (Xie standard protocol for the TRIzol reagent (Life technolo- et al. 2011). gies, California, USA). RNA integrity and concentration were checked using an Agilent 2100 Bioanalyzer (Agi- DNA Methylation analysis by bisuphite sequencing lent Technologies, Inc., Santa Clara, CA, USA). mRNA was isolated from total RNA using a NEB- The DNA of each larval sample was
Load more

Recommended publications
  • Innovation and Robustness in Complex Regulatory Gene Networks
    Innovation and robustness in complex regulatory gene networks S. Ciliberti*, O. C. Martin*†, and A. Wagner‡§ *Unite´Mixte Recherche 8565, Laboratoire de Physique The´orique et Mode`les Statistiques, Universite´Paris-Sud and Centre National de la Recherche Scientifique, F-91405 Orsay, France; †Unite´Mixte de Recherche 820, Laboratoire de Ge´ne´ tique Ve´ge´ tale, L’Institut National de la Recherche Agronomique, Ferme du Moulon, F-91190 Gif-sur-Yvette, France; and ‡Department of Biochemistry, University of Zurich, Y27-J-54, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland Communicated by Giorgio Parisi, University of Rome, Rome, Italy, June 20, 2007 (received for review November 24, 2006) The history of life involves countless evolutionary innovations, a environmental variation. Mutational robustness means that a steady stream of ingenuity that has been flowing for more than 3 system produces little phenotypic variation when subjected to billion years. Very little is known about the principles of biological genotypic variation caused by mutations. At first sight, such organization that allow such innovation. Here, we examine these robustness might pose a problem for evolutionary innovation, principles for evolutionary innovation in gene expression patterns. because a robust system cannot produce much of the variation To this end, we study a model for the transcriptional regulation that can become the basis for evolutionary innovation. networks that are at the heart of embryonic development. A As we shall see, there is some truth to this appearance, but it genotype corresponds to a regulatory network of a given topol- is in other respects flawed. Robustness and the ability to innovate ogy, and a phenotype corresponds to a steady-state gene expres- cannot only coexist, but the first may be a precondition for the sion pattern.
    [Show full text]
  • Transformations of Lamarckism Vienna Series in Theoretical Biology Gerd B
    Transformations of Lamarckism Vienna Series in Theoretical Biology Gerd B. M ü ller, G ü nter P. Wagner, and Werner Callebaut, editors The Evolution of Cognition , edited by Cecilia Heyes and Ludwig Huber, 2000 Origination of Organismal Form: Beyond the Gene in Development and Evolutionary Biology , edited by Gerd B. M ü ller and Stuart A. Newman, 2003 Environment, Development, and Evolution: Toward a Synthesis , edited by Brian K. Hall, Roy D. Pearson, and Gerd B. M ü ller, 2004 Evolution of Communication Systems: A Comparative Approach , edited by D. Kimbrough Oller and Ulrike Griebel, 2004 Modularity: Understanding the Development and Evolution of Natural Complex Systems , edited by Werner Callebaut and Diego Rasskin-Gutman, 2005 Compositional Evolution: The Impact of Sex, Symbiosis, and Modularity on the Gradualist Framework of Evolution , by Richard A. Watson, 2006 Biological Emergences: Evolution by Natural Experiment , by Robert G. B. Reid, 2007 Modeling Biology: Structure, Behaviors, Evolution , edited by Manfred D. Laubichler and Gerd B. M ü ller, 2007 Evolution of Communicative Flexibility: Complexity, Creativity, and Adaptability in Human and Animal Communication , edited by Kimbrough D. Oller and Ulrike Griebel, 2008 Functions in Biological and Artifi cial Worlds: Comparative Philosophical Perspectives , edited by Ulrich Krohs and Peter Kroes, 2009 Cognitive Biology: Evolutionary and Developmental Perspectives on Mind, Brain, and Behavior , edited by Luca Tommasi, Mary A. Peterson, and Lynn Nadel, 2009 Innovation in Cultural Systems: Contributions from Evolutionary Anthropology , edited by Michael J. O ’ Brien and Stephen J. Shennan, 2010 The Major Transitions in Evolution Revisited , edited by Brett Calcott and Kim Sterelny, 2011 Transformations of Lamarckism: From Subtle Fluids to Molecular Biology , edited by Snait B.
    [Show full text]
  • Synergism Between Chromatin Dynamics and Gene Transcription
    bioRxiv preprint doi: https://doi.org/10.1101/2021.05.17.444405; this version posted May 17, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Synergism between Chromatin Dynamics and Gene Transcription 2 Enhances Robustness and Stability of Epigenetic Cell Memory 3 Zihao Wang1,2, Songhao Luo1,2, Meiling Chen1,2, Tianshou Zhou1,2,*, and Jiajun Zhang1,2,† 4 1 Key Laboratory of Computational Mathematics, Guangdong Province 5 2 School of Mathematics, Sun Yat-Sen University, Guangzhou, 510275, P. R. China 6 *[email protected], †[email protected] 7 8 Abstract 9 Apart from carrying hereditary information inherited from their ancestors and being able to pass on 10 the information to their descendants, cells can also inherit and transmit information that is not stored 11 as changes in their genome sequence. Such epigenetic cell memory, which is particularly important 12 in multicellular organisms, involves multiple biochemical modules mainly including chromatin 13 organization, epigenetic modification and gene transcription. The synergetic mechanism among 14 these three modules remains poorly understood and how they collaboratively affect the robustness 15 and stability of epigenetic memory is unclear either. Here we developed a multiscale model to 16 address these questions. We found that the chromatin organization driven by long-range epigenetic 17 modifications can significantly enhance epigenetic cell memory and its stability in contrast to that 18 driven by local interaction and that chromatin topology and gene activity can promptly and 19 simultaneously respond to changes in nucleosome modifications while maintaining the robustness 20 and stability of epigenetic cell memory over several cell cycles.
    [Show full text]
  • Multi-Enhancer Transcriptional Hubs Confer Phenotypic Robustness Albert Tsai1†*, Mariana RP Alves1,2†, Justin Crocker1*
    RESEARCH ADVANCE Multi-enhancer transcriptional hubs confer phenotypic robustness Albert Tsai1†*, Mariana RP Alves1,2†, Justin Crocker1* 1European Molecular Biology Laboratory, Heidelberg, Germany; 2Collaboration for joint PhD degree between EMBL and Heidelberg University, Faculty of Biosciences, Heidelberg, Germany Abstract We previously showed in Drosophila melanogaster embryos that low-affinity Ultrabithorax (Ubx)-responsive shavenbaby (svb) enhancers drive expression using localized transcriptional environments and that active svb enhancers on different chromosomes tended to colocalize (Tsai et al., 2017). Here, we test the hypothesis that these multi-enhancer ‘hubs’ improve phenotypic resilience to stress by buffering against decreases in transcription factor concentrations and transcriptional output. Deleting a redundant enhancer from the svb locus led to reduced trichome numbers in embryos raised at elevated temperatures. Using high-resolution fluorescence microscopy, we observed lower Ubx concentration and transcriptional output in this deletion allele. Transcription sites of the full svb cis-regulatory region inserted into a different chromosome colocalized with the svb locus, increasing Ubx concentration, the transcriptional output of svb, and partially rescuing the phenotype. Thus, multiple enhancers could reinforce a local transcriptional hub to buffer against environmental stresses and genetic perturbations, providing a mechanism for phenotypical robustness. DOI: https://doi.org/10.7554/eLife.45325.001 *For correspondence:
    [Show full text]
  • The Robustness and Evolvability of Transcription Factor Binding Sites Joshua L
    REPORTS drogel showed practically no hysteresis, at least drogels with a higher amount of cleavable link- 16. Q. Wang et al., Nature 463, 339–343 (2010). when stretched less than fourfold, which indi- ages are subject to faster degradation. Our results 17. M. Heskins, J. E. Guillet, J. Macromol. Sci. A Chem. 2, 1441 (1968). cates that the elongation did not break the co- demonstrate that the swelling suppression of 18. J. E. Chung, M. Yokoyama, T. Aoyagi, Y. Sakurai, valent bonds of the polymer network (Fig. 3C). hydrogels may help maintain their initial shape T. Okano, J. Control. Release 53, 119–130 (1998). This reversible feature is prominent when com- and retain their mechanical properties under phys- 19.J.Cui,M.A.Lackey,G.N.Tew,A.J.Crosby,Macromolecules pared with the hydrogels that exhibit hysteresis iological conditions. 45, 6104–6110 (2012). 20. J. Li et al., Biomaterials 27, 4132–4140 (2006). during deformation, which essentially fail to 21. S. Reinicke et al., Soft Matter 5, 2648 (2009). tolerate a continual mechanical load. In contrast to References and Notes 22. S. P. Obukhov, M. Rubinstein, R. H. Colby, Macromolecules – such hydrogels, our hydrogels showed no swell- 1. K. Y. Lee, D. J. Mooney, Chem. Rev. 101, 1869 1880 27, 3191–3198 (1994). ing or weakening in aqueous media even after a (2001). 2. G. D. Nicodemus, S. J. Bryant, Tissue Eng. Part B Rev. 14, Acknowledgments: This work was supported by the Japan repetitive mechanical overload. The nonswellable – 149 165 (2008). Society for the Promotion of Science ( JSPS) through the – hydrogel endured a compressive stress of up 3.
    [Show full text]
  • Negative Feedback Confers Mutational Robustness in Yeast Transcription Factor Regulation
    Negative feedback confers mutational robustness in yeast transcription factor regulation Charles M. Denbya, Joo Hyun Ima, Richard C. Yub, C. Gustavo Pesceb, and Rachel B. Brema,1 aDepartment of Molecular and Cell Biology, University of California, Berkeley, CA 94720-3220; and bMolecular Sciences Institute, Berkeley, CA 94704 Edited* by Susan Lindquist, Whitehead Institute for Biomedical Research, Cambridge, MA, and approved January 26, 2012 (received for review October 5, 2011) Organismal fitness depends on the ability of gene networks to determinant of quantitative behaviors of inducible circuits (20– function robustly in the face of environmental and genetic 24), we also investigated the role of Rox1 feedback in expression perturbations. Understanding the mechanisms of this stability is regulation during oxygen response. one of the key aims of modern systems biology. Dissecting the basis of robustness to mutation has proven a particular challenge, Results with most experimental models relying on artificial DNA sequence We set out to establish a tractable model system for the study of variants engineered in the laboratory. In this work, we hypothe- feedback and robustness using yeast transcription factors. For sized that negative regulatory feedback could stabilize gene this purpose, we first screened transcription factor genes for expression against the disruptions that arise from natural genetic feedback on protein abundance. We used fluorescence micros- variation. We screened yeast transcription factors for feedback copy (25) to measure protein expression from a single genomic and used the results to establish ROX1 (Repressor of hypOXia) as copy of each factor tagged with GFP in a diploid strain (26) while a model system for the study of feedback in circuit behaviors and varying levels of an untagged copy of the factor (Fig.
    [Show full text]
  • Rapid Evolution of Mammalian X-Linked Testis-Expressed Homeobox Genes
    Copyright 2004 by the Genetics Society of America DOI: 10.1534/genetics.103.025072 Rapid Evolution of Mammalian X-Linked Testis-Expressed Homeobox Genes Xiaoxia Wang and Jianzhi Zhang1 Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, Michigan 48109 Manuscript received November 26, 2003 Accepted for publication February 11, 2004 ABSTRACT Homeobox genes encode transcription factors that function in various developmental processes and are usually evolutionarily conserved in their sequences. However, two X-chromosome-linked testis-expressed homeobox genes, one from rodents and the other from fruit flies, are known to evolve rapidly under positive Darwinian selection. Here we report yet another case, from primates. TGIFLX is an X-linked homeobox gene that originated by retroposition of the autosomal gene TGIF2, most likely in a common ancestor of rodents and primates. While TGIF2 is ubiquitously expressed, TGIFLX is exclusively expressed in adult testis. A comparison of the TGIFLX sequences among 16 anthropoid primates revealed a signifi- cantly higher rate of nonsynonymous nucleotide substitution (dN) than synonymous substitution (dS), strongly suggesting the action of positive selection. Although the high dN/dS ratio is most evident outside ف the homeobox, the homeobox has a dN/dS of 0.89 and includes two codons that are likely under selection. Furthermore, the rate of radical amino acid substitutions that alter amino acid charge is significantly greater than that of conservative substitutions, suggesting that the selection promotes diversity of the protein charge profile. More interestingly, an analysis of 64 orthologous homeobox genes from humans and mice shows substantially higher rates of amino acid substitution in X-linked testis-expressed genes than in other genes.
    [Show full text]
  • Phenotypic Robustness and the Assortativity Signature of Human Transcription Factor Networks
    Dartmouth College Dartmouth Digital Commons Dartmouth Scholarship Faculty Work 8-14-2014 Phenotypic Robustness and the Assortativity Signature of Human Transcription Factor Networks Dov A. Pechenick Dartmouth College Joshua L. Payne University of Zurich Jason H. Moore Dartmouth College Follow this and additional works at: https://digitalcommons.dartmouth.edu/facoa Part of the Biology Commons, and the Computational Biology Commons Dartmouth Digital Commons Citation Pechenick, Dov A.; Payne, Joshua L.; and Moore, Jason H., "Phenotypic Robustness and the Assortativity Signature of Human Transcription Factor Networks" (2014). Dartmouth Scholarship. 1623. https://digitalcommons.dartmouth.edu/facoa/1623 This Article is brought to you for free and open access by the Faculty Work at Dartmouth Digital Commons. It has been accepted for inclusion in Dartmouth Scholarship by an authorized administrator of Dartmouth Digital Commons. For more information, please contact [email protected]. Phenotypic Robustness and the Assortativity Signature of Human Transcription Factor Networks Dov A. Pechenick1, Joshua L. Payne2, Jason H. Moore1* 1 Computational Genetics Laboratory, Dartmouth College, Hanover, New Hampshire, United States of America, 2 Institute of Evolutionary Biology and Environmental Studies, University of Zurich, Zurich, Switzerland Abstract Many developmental, physiological, and behavioral processes depend on the precise expression of genes in space and time. Such spatiotemporal gene expression phenotypes arise from the binding of sequence-specific transcription factors (TFs) to DNA, and from the regulation of nearby genes that such binding causes. These nearby genes may themselves encode TFs, giving rise to a transcription factor network (TFN), wherein nodes represent TFs and directed edges denote regulatory interactions between TFs. Computational studies have linked several topological properties of TFNs — such as their degree distribution — with the robustness of a TFN’s gene expression phenotype to genetic and environmental perturbation.
    [Show full text]
  • Robustness, Evolvability, and the Logic of Genetic Regulation
    Robustness, Evolvability, and the Joshua L. Payne*,** Logic of Genetic Regulation University of Zurich Jason H. Moore† Dartmouth College ‡ Andreas Wagner University of Zurich The Santa Fe Institute Abstract In gene regulatory circuits, the expression of individual genes is commonly modulated by a set of regulating gene products, which bind to a geneʼs cis-regulatory region. This region encodes an input-output function, referred to as signal-integration logic, that maps a specific combination of regulatory signals (inputs) to a particular expression state (output) of a gene. The space of all possible signal- Keywords integration functions is vast and the mapping from input to output Evolutionary innovation, random Boolean is many-to-one: For the same set of inputs, many functions (genotypes) circuit, genetic regulation, genotype yield the same expression output (phenotype). Here, we exhaustively networks, genotype-phenotype map enumerate the set of signal-integration functions that yield identical gene expression patterns within a computational model of gene regulatory circuits. Our goal is to characterize the relationship between robustness and evolvability in the signal-integration space of regulatory circuits, and to understand how these properties vary between the genotypic and phenotypic scales. Among other results, we find that the distributions of genotypic robustness are skewed, so that the majority of signal- integration functions are robust to perturbation. We show that the connected set of genotypes that make up a given phenotype are constrained to specific regions of the space of all possible signal- integration functions, but that as the distance between genotypes increases, so does their capacity for unique innovations.
    [Show full text]
  • Robustness and Evolvability: a Paradox Resolved
    Proc. R. Soc. B (2008) 275, 91–100 doi:10.1098/rspb.2007.1137 Published online 31 October 2007 Robustness and evolvability: a paradox resolved Andreas Wagner1,2,3,* 1Department of Biochemistry, University of Zurich, 8057 Zurich, Switzerland 2The Santa Fe Institute, Santa Fe, NM 87501, USA 3Swiss Institute of Bioinformatics, 4056 Basel, Switzerland Understanding the relationship between robustness and evolvability is key to understand how living things can withstand mutations, while producing ample variation that leads to evolutionary innovations. Mutational robustness and evolvability, a system’s ability to produce heritable variation, harbour a paradoxical tension. On one hand, high robustness implies low production of heritable phenotypic variation. On the other hand, both experimental and computational analyses of neutral networks indicate that robustness enhances evolvability. I here resolve this tension using RNA genotypes and their secondary structure phenotypes as a study system. Toresolve the tension, one must distinguish between robustness of a genotype and a phenotype. I confirm that genotype (sequence) robustness and evolvability share an antagonistic relationship. In stark contrast, phenotype (structure) robustness promotes structure evolvability. A consequence is that finite populations of sequences with a robust phenotype can access large amounts of phenotypic variation while spreading through a neutral network. Population-level processes and phenotypes rather than individual sequences are key to understand the relationship between robustness and evolvability. My observations may apply to other genetic systems where many connected genotypes produce the same phenotypes. Keywords: evolvability; molecular evolution; neutral networks 1. INTRODUCTION robust a system is, the less phenotypic variation a given Robustness and evolvability are fundamental properties of number of mutations generate and hence the less evolvable biological systems.
    [Show full text]
  • The Relationship Between Robustness and Evolution 1 1,2 1,2,3,4 2 Pengyao Jiang , Martin Kreitman , John Reinitz
    bioRxiv preprint doi: https://doi.org/10.1101/268862; this version posted February 22, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 The relationship between robustness and evolution 1 1,2 1,2,3,4 2 Pengyao Jiang , Martin Kreitman , John Reinitz 3 1 Department of Ecology & Evolution, University of Chicago, IL 60637, USA 4 2 Institute for Genomics & Systems Biology, Chicago, IL 60637, USA 5 3 Department of Statistics, University of Chicago, IL 60637, USA 6 4 Department of Molecular Genetics and Cell Biology, University of Chicago, IL 60637, 7 USA 8 Keywords 9 canalization; adaptation; Boolean model; Wright-Fisher; population simulations; perceptron; 10 evolutionary capacitor 1 bioRxiv preprint doi: https://doi.org/10.1101/268862; this version posted February 22, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 11 Abstract 12 Developmental robustness (canalization) is a common attribute of traits in multi-cellular 13 organisms. High robustness ensures the reproducibility of phenotypes in the face of envi- 14 ronmental and developmental noise, but it also dampens the expression of genetic mutation, 15 the fuel for adaptive evolution. A reduction in robustness may therefore be adaptive under 16 certain evolutionary scenarios.
    [Show full text]
  • Robustness and Applicability of Transcription Factor and Pathway Analysis Tools on Single-Cell RNA-Seq Data Christian H
    Holland et al. Genome Biology (2020) 21:36 https://doi.org/10.1186/s13059-020-1949-z RESEARCH Open Access Robustness and applicability of transcription factor and pathway analysis tools on single-cell RNA-seq data Christian H. Holland1,2, Jovan Tanevski1,3, Javier Perales-Patón1, Jan Gleixner4,5, Manu P. Kumar6, Elisabetta Mereu7, Brian A. Joughin6,8, Oliver Stegle4,5,9, Douglas A. Lauffenburger6, Holger Heyn7,10, Bence Szalai11 and Julio Saez-Rodriguez1,2* Abstract Background: Many functional analysis tools have been developed to extract functional and mechanistic insight from bulk transcriptome data. With the advent of single-cell RNA sequencing (scRNA-seq), it is in principle possible to do such an analysis for single cells. However, scRNA-seq data has characteristics such as drop-out events and low library sizes. It is thus not clear if functional TF and pathway analysis tools established for bulk sequencing can be applied to scRNA-seq in a meaningful way. Results: To address this question, we perform benchmark studies on simulated and real scRNA-seq data. We include the bulk-RNA tools PROGENy, GO enrichment, and DoRothEA that estimate pathway and transcription factor (TF) activities, respectively, and compare them against the tools SCENIC/AUCell and metaVIPER, designed for scRNA-seq. For the in silico study, we simulate single cells from TF/pathway perturbation bulk RNA-seq experiments. We complement the simulated data with real scRNA-seq data upon CRISPR-mediated knock-out. Our benchmarks on simulated and real data reveal comparable performance to the original bulk data. Additionally, we show that the TF and pathway activities preserve cell type-specific variability by analyzing a mixture sample sequenced with 13 scRNA-seq protocols.
    [Show full text]