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Can the “molecular stuff” waittill university? – Opportunitiesfor molecular genetics in the
classroom
Andrew MooreProgramme Manager for Science & SocietyEuropean Molecular Biology Organization
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The (deplorable) situation in schoolsacross Europe
Representation of some key areas of molecular genetics
Informal survey conducted by EMBO in 2007
Principles ofbioinformatics
Almost absent(some Germanregions; someUK examboards).
Principles ofmolecular medicine
1 in 7 countriesexplain suchapproaches to diseasestudy and treatment.
Molecular evolution(phylogeny)
At most 30%coverage across allsecondary curricula.
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A mention is all it takes to capturestudent’s fascination. Here are some
examples of fascinating topics that couldbe used to introduce the concept of
molecular medicine in school lessons:
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Molecular medicine 1
Gleevec (imatinib mesylate (STI571))Rational drug design to avoid severe side-effects of chemotherapy
Molecular genetics –>identification ofchromosomaltranslocation(Philadelphiachromosome) thatfuses part of Bcr (Chr.22) with Abl (Chr. 9), atyrosine kinase.
Bcr-Abl homodimer:continuously active,and activates a cascadeof cell cycle proteins–> uncontrolledproliferation –> cancer.
Work (pioneered byBrian Druker) towardsrationally designing achemical agent toselectively inactivateBcr-Abl producesGleevec, the“leukaemia pill”. Phase1 clinical trials 1999.
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Molecular medicine 2
PharmacogenomicsGenotyping with the aim of correct prescription and patient group-specific drugdevelopment
USA: annually >100.000 deaths due toadverse reactions toFDA-approved drugs(>2 million AR intotal).
Individual differencesin liver detoxificationenzymes are importantfactor in toxicity andefficacy of many drugs.
Cytochrome P450genotyping test nowexists: relevant to morethan 30 groups ofdrugs.
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Molecular medicine 3
Genotyping ofindividuals in Africanpopulations –>molecular geneticvariation in the ABOblood alleles to identifypeople with muchgreater risk of severeinfections of P.falciparum.
Molecular genetics of Malaria parasites and vaccine developmentMolecular genetics of Malaria vectors and host-parasite interaction
Genotyping ofmosquitoes enablesunderstanding ofgenetic origins ofdifferential resistanceto the malarialparasite .
P. falciparum genomesequence significantlyaccelerates the search fornew targets fortherapeutics, and antigensfor vaccine developmente.g. cloning of P.falciparum exonsequences into plasmidsfor DNA vaccine screens.
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Some European education resources inmolecular genetics and bioinformatics
• Xlab, Göttingen: www.xlab-goettingen.de
• Gläsernes Labor, Berlin: www.glaesernes-labor.de
• École de l’ADN, Nimes: www.ecole-adn.fr
• European Learning Lab for the Life Sciences at theEuropean Molecular Biology Laboratory (EMBL):www-db.embl.de/jss/EmblGroupsOrg/g_213.html
• European Molecular Biology Organization (EMBO):www.embo.org/scisoc/tw03biocomputing.pdf
• Life Learning Centre, Torino: www.llctorino.it/index.php
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Molecular evolution –an urgent case
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What is molecular evolution?
• Chemical evolution of life?
• Base-pair mutation in DNA or RNA?
• Building of evolutionary trees using DNA/proteinsequence data?
Molecular Evolution = Molecular Phylogenetics / Phylogeny
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Basics of molecular phylogeny
Concept of“Molecular clocks”e.g. haemoglobin,cytochrome C
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A (very) brief history of molecular phylogenetics
Protein sequencecomparisons,e.g. globin genes
1960s
Evolving Genes and Proteins, Ed. Bryson, V. and Vogel, H. J., (1965) Academic Press, New York
Higher primatesgenome-widecomparisons
2001 – 2007
Chen, F.-C., and Li, W.-H. (2001). Genomic divergences between humans and other hominoidsand the effective population size of the common ancestor of humans and chimpanzees. Am J HumGenet/ 68: 444 – 56
Ebersberger, I. et al. (2007). Mapping human genetic ancestry. Mol Biol Evol/ 24: 2266 – 76
Archaea/Bacteria16S rRNAcomparisons
1977
Woese, C. and Fox, G. (1977) Phylogenetic structure of the prokaryotic domain: the primarykingdoms. Proceedings of the National Academies of Science (PNAS), USA, 74 (11): 5088 – 90
“New animal phylogeny”
2000
Adouette, A. et al. (2000) The new animal phylogeny: Reliability and implications. Proceedingsof the National Academies of Science (PNAS), USA, 97 (9): 4453 – 56
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DNA sequences are the ultimate forensicevidence supporting Darwin’s original
theory of evolution.
Why is molecular evolution important?
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Molecular evolution must be taught in schoolsalongside similarity of form, embryology andphysiology, and the fossil record, because...
It addresses the very source of species-relatedphenotypic variation using large amounts of
directly comparable biological data (genesequences) and is therefore scientifically robust.
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Molecular phylogenetics often overturns oldolder theories of evolutionary relatedness:
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1 Primitive kingdoms of life
Bacteria Archae-bacteria
Eukarya
Traditional: comparison ofintracellular architecture andcell wall structure.
Bacteria Archaea Eukarya
Molecular: comparison of16S rRNA sequences.
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A B
2 The “New Animal Phylogeny”
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3 Mammalia – superordinal classifications
Morphological phylogeny:
Ungulata: hyraxes; elephants; manatees and dugongs; horses,tapirs and rhinos; camels, pigs and cows; whales and porpoises;(aardvarks)Molecular phylogeny:Afrotheria: hyraxes; elephants; manatees and dugongs;aardvarks; golden moles and tenrecs, elephant shrewsLaurasiatheria: hedgehogs, moles and shrews; bats; horses, tapirsand rhinos; camels, pigs, cows hippos, whales and porpoises;dogs, bears and cats; pangolins
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http://www.zi.ku.dk/evolbiology/courses/ME04/7_9/springer200-phyl.pdf
Molecules consolidate the placental mammal tree
Mark S. Springer, Michael J. Stanhope, Ole Madsen andWilfried W. de Jong
Trends in Ecology and Evolution
Article in press
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http://www.zi.ku.dk/evolbiology/courses/ME04/7_9/springer200-phyl.pdfSCA 1
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http://www.zi.ku.dk/evolbiology/courses/ME04/7_9/springer200-phyl.pdf
BRCA 1
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Genome-wide molecular phylogenetics is ouronly hope between very closely related species:
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Genome-wide comparisons of codingsequences (genes), % differences:
Source: Wolfgang Enard, Max-Planck-Institute of Evolutionary Anthropology, Leipzig, Germany
Human Chimpanzee1.2%
Human Gorilla1.7%
Chimpanzee Gorilla1.7%
Human Orangutan3%
Chimpanzee Orangutan3%
Gorilla Orangutan3%
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Source: Wolfgang Enard, Max-Planck-Institute of Evolutionary Anthropology, Leipzig, Germany
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Where are the molecular evolutionteaching resources and information?
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Unfortunately there are very few inEurope; most resources are to be
found in the USA:
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http://www.ncbi.nlm.nih.gov/About/primer/phylo.html
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http://www.nsta.org/
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http://www.megasoftware.net/
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The Making of The Fittest, Sean B. Carroll (2006)
If a successful popular science book can be written about molecularevolution, this “molecular stuff” certainly can’t wait till university...
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DNA to Darwin: www.dnadarwin.org/
See Volvox for resources in a range of languages: www.eurovolvox.org
But, coming soon to Europe...
An education initiative on modernmethods in evolutionary study:
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http://en.wikipedia.org/wiki/Evolution_of_mammals
http://en.wikipedia.org/wiki/Molecular_phylogeny
Wikipedia also has pretty good entrieson molecular evolution...
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http://www.embo.org/scisoc/teachers_wk07report.pdf
For details of the EMBO report onmolecular genetics education in Europe...