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  • 1
    Publication Date: 2010-03-12
    Description: The relationship between the genotype and the phenotype, or the genotype-phenotype map, is generally approached with the tools of multivariate quantitative genetics and morphometrics. Whereas studies of development and mathematical models of development may offer new insights into the genotype-phenotype map, the challenge is to make them useful at the level of microevolution. Here we report a computational model of mammalian tooth development that combines parameters of genetic and cellular interactions to produce a three-dimensional tooth from a simple tooth primordia. We systematically tinkered with each of the model parameters to generate phenotypic variation and used geometric morphometric analyses to identify, or developmentally ordinate, parameters best explaining population-level variation of real teeth. To model the full range of developmentally possible morphologies, we used a population sample of ringed seals (Phoca hispida ladogensis). Seal dentitions show a high degree of variation, typically linked to the lack of exact occlusion. Our model suggests that despite the complexity of development and teeth, there may be a simple basis for dental variation. Changes in single parameters regulating signalling during cusp development may explain shape variation among individuals, whereas a parameter regulating epithelial growth may explain serial, tooth-to-tooth variation along the jaw. Our study provides a step towards integrating the genotype, development and the phenotype.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Salazar-Ciudad, Isaac -- Jernvall, Jukka -- England -- Nature. 2010 Mar 25;464(7288):583-6. doi: 10.1038/nature08838. Epub 2010 Mar 10.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Departament de Genetica i Microbiologia, Facultat de Biociencies, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona, Spain. isaac.salazar@uab.cat〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20220757" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Gene Regulatory Networks/genetics ; Genotype ; *Models, Biological ; Phenotype ; *Phoca/anatomy & histology/genetics/growth & development ; Signal Transduction ; Tooth/*anatomy & histology/growth & development/*physiology
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-05-03
    Description: It is not known whether natural selection can encounter any given phenotype that can be produced by genetic variation. There has been a long-lasting debate about the processes that limit adaptation and, consequently, about how well adapted phenotypes are. Here we examine how development may affect adaptation, by decomposing the genotype-fitness map-the association between each genotype and its fitness-into two: one mapping genotype to phenotype by means of a computational model of organ development, and one mapping phenotype to fitness. In the map of phenotype and fitness, the fitness of each individual is based on the similarity between realized morphology and optimal morphology. We use three different simulations to map phenotype to fitness, and these differ in the way in which similarity is calculated: similarity is calculated for each trait (in terms of each cell position individually), for a large or a small number of phenotypic landmarks (the 'many-traits' and 'few-traits' phenotype-fitness maps), and by measuring the overall surface roughness of morphology (the 'roughness' phenotype-fitness map). Evolution is simulated by applying the genotype-phenotype map and one phenotype-fitness map to each individual in the population, as well as random mutation and drift. We show that the complexity of the genotype-phenotype map prevents substantial adaptation in some of the phenotype-fitness maps: sustained adaptation is only possible using 'roughness' or 'few-traits' phenotype-fitness maps. The results contribute developmental understanding to the long-standing question of which aspects of phenotype can be effectively optimized by natural selection.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Salazar-Ciudad, Isaac -- Marin-Riera, Miquel -- England -- Nature. 2013 May 16;497(7449):361-4. doi: 10.1038/nature12142. Epub 2013 May 1.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Evolutionary phenomics group. Developmental Biology Program, Institute of Biotechnology, University of Helsinki, PO Box 56, FIN-00014 Helsinki, Finland. isaac.salazar@uab.cat〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23636325" target="_blank"〉PubMed〈/a〉
    Keywords: Adaptation, Physiological/*genetics ; Algorithms ; Biological Evolution ; Computer Simulation ; Genetic Fitness/genetics ; *Genotype ; *Models, Biological ; *Phenotype ; Population Density ; Principal Component Analysis ; Selection, Genetic ; Tooth/anatomy & histology/*growth & development
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 3
    Publication Date: 2014-08-01
    Description: The evolutionary relationships of extinct species are ascertained primarily through the analysis of morphological characters. Character inter-dependencies can have a substantial effect on evolutionary interpretations, but the developmental underpinnings of character inter-dependence remain obscure because experiments frequently do not provide detailed resolution of morphological characters. Here we show experimentally and computationally how gradual modification of development differentially affects characters in the mouse dentition. We found that intermediate phenotypes could be produced by gradually adding ectodysplasin A (EDA) protein in culture to tooth explants carrying a null mutation in the tooth-patterning gene Eda. By identifying development-based character inter-dependencies, we show how to predict morphological patterns of teeth among mammalian species. Finally, in vivo inhibition of sonic hedgehog signalling in Eda null teeth enabled us to reproduce characters deep in the rodent ancestry. Taken together, evolutionarily informative transitions can be experimentally reproduced, thereby providing development-based expectations for character-state transitions used in evolutionary studies.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252015/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4252015/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Harjunmaa, Enni -- Seidel, Kerstin -- Hakkinen, Teemu -- Renvoise, Elodie -- Corfe, Ian J -- Kallonen, Aki -- Zhang, Zhao-Qun -- Evans, Alistair R -- Mikkola, Marja L -- Salazar-Ciudad, Isaac -- Klein, Ophir D -- Jernvall, Jukka -- DP2 OD007191/OD/NIH HHS/ -- DP2-OD007191/OD/NIH HHS/ -- K99 DE024214/DE/NIDCR NIH HHS/ -- R01 DE021420/DE/NIDCR NIH HHS/ -- R01-DE021420/DE/NIDCR NIH HHS/ -- England -- Nature. 2014 Aug 7;512(7512):44-8. doi: 10.1038/nature13613. Epub 2014 Jul 30.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Developmental Biology Program, Institute of Biotechnology, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland. ; 1] Program in Craniofacial and Mesenchymal Biology, University of California, San Francisco, San Francisco, California 94114, USA [2] Department of Orofacial Sciences, University of California, San Francisco, San Francisco, California 94114, USA. ; Division of Materials Physics, Department of Physics, University of Helsinki, P.O. Box 64, FIN-00014 Helsinki, Finland. ; Key Laboratory of Evolutionary Systematics of Vertebrates, Institute of Vertebrate Paleontology and Paleoanthropology, Chinese Academy of Sciences, Beijing 100044, China. ; 1] School of Biological Sciences, Monash University, Victoria 3800, Australia [2] Geosciences, Museum Victoria, GPO Box 666, Melbourne, Victoria 3001, Australia. ; 1] Developmental Biology Program, Institute of Biotechnology, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland [2] Genomics, Bioinformatics and Evolution Group. Department de Genetica i Microbiologia, Universitat Autonoma de Barcelona, Cerdanyola del Valles 08193, Spain. ; 1] Program in Craniofacial and Mesenchymal Biology, University of California, San Francisco, San Francisco, California 94114, USA [2] Department of Orofacial Sciences, University of California, San Francisco, San Francisco, California 94114, USA [3] Department of Pediatrics, University of California, San Francisco, San Francisco, California 94114, USA [4] Institute for Human Genetics, University of California, San Francisco, San Francisco, California 94114, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25079326" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; *Biological Evolution ; Computer Simulation ; Ectodysplasins/deficiency/genetics/pharmacology ; Female ; *Fossils ; Gene Deletion ; Hedgehog Proteins/antagonists & inhibitors/genetics ; In Vitro Techniques ; Male ; Mice ; Molar/anatomy & histology/drug effects/growth & development ; Phenotype ; Signal Transduction/drug effects ; Tooth/*anatomy & histology/drug effects/*growth & development
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 2002-06-04
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 5
    Publication Date: 2006-11-22
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
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  • 6
    Publication Date: 2018-11-29
    Description: An increasing number of mammalian species have been shown to have a history of hybridization and introgression based on genetic analyses. Only relatively few fossils, however, preserve genetic material, and morphology must be used to identify the species and determine whether morphologically intermediate fossils could represent hybrids. Because dental and cranial fossils are typically the key body parts studied in mammalian palaeontology, here we bracket the potential for phenotypically extreme hybridizations by examining uniquely preserved cranio-dental material of a captive hybrid between grey and ringed seals. We analysed how distinct these species are genetically and morphologically, how easy it is to identify the hybrids using morphology and whether comparable hybridizations happen in the wild. We show that the genetic distance between these species is more than twice the modern human–Neanderthal distance, but still within that of morphologically similar species pairs known to hybridize. By contrast, morphological and developmental analyses show grey and ringed seals to be highly disparate, and that the hybrid is a predictable intermediate. Genetic analyses of the parent populations reveal introgression in the wild, suggesting that grey–ringed seal hybridization is not limited to captivity. Taken together, we postulate that there is considerable potential for mammalian hybridization between phenotypically disparate taxa.
    Keywords: palaeontology, genetics, developmental biology
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
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  • 7
    Publication Date: 2018-07-03
    Description: Quantitative genetic variation in morphology is pervasive in all species and is the basis for the evolution of differences among species. The measurement of morphological form in adults is now beginning to be combined with comparable measurements of form during development. Here we compare the shape of the developing wing to its adult form in a holometabolous insect, Drosophila melanogaster . We used protein expression patterns to measure shape in the developing precursors of the final adult wing. Three developmental stages were studied: late larval third instar, post-pupariation and in the adult fly. We studied wild-type animals in addition to mutants of two genes ( shf and ds ) that have known effects on adult wing shape and size. Despite experimental noise related to the difficulty of comparing developing structures, we found consistent differences in wing shape and size at each developmental stage between genotypes. Quantitative comparisons of variation arising at different developmental stages with the variation in the final structure enable us to determine when variation arises, and to generate hypotheses about the causes of that variation. In addition we provide linear rules allowing us to link wing morphology in the larva, with wing morphology in the pupa. Our approach provides a framework to analyze quantitative morphological variation in the developing fly wing. This framework should help to characterize the natural variation of the larval and pupal wing shape, and to measure the contribution of the processes occurring during these developmental stages to the natural variation in adult wing morphology.
    Electronic ISSN: 2160-1836
    Topics: Biology
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  • 8
    Publication Date: 2016-01-10
    Description: Motivation: The transformation of the embryo during development requires complex gene networks, cell signaling and gene-regulated cell behaviors (division, adhesion, polarization, apoptosis, contraction, extracellular matrix secretion, signal secretion and reception, etc.). There are several models of development implementing these phenomena, but none considers at the same time the very different bio-mechanical properties of epithelia, mesenchyme, extracellular matrix and their interactions. Results: Here, we present a new computational model and accompanying open-source software, EmbryoMaker, that allows the user to simulate custom developmental processes by designing custom gene networks capable of regulating cell signaling and all animal basic cell behaviors. We also include an editor to implement different initial conditions, mutations and experimental manipulations. We show the applicability of the model by simulating several complex examples of animal development. Availability and implementation: The source code can be downloaded from: http://www.biocenter.helsinki.fi/salazar/software.html . Contact: isalazar@mappi.helsinki.fi Supplementary information: Supplementary data are available at Bioinformatics online.
    Print ISSN: 1367-4803
    Electronic ISSN: 1460-2059
    Topics: Biology , Computer Science , Medicine
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