Can the “molecular stuff” waittill university? – Opportunitiesfor molecular genetics in the

classroom

Andrew MooreProgramme Manager for Science & SocietyEuropean Molecular Biology Organization

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.

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:

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.

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.

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.

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

Molecular evolution –an urgent case

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

Basics of molecular phylogeny

Concept of“Molecular clocks”e.g. haemoglobin,cytochrome C

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

DNA sequences are the ultimate forensicevidence supporting Darwin’s original

theory of evolution.

Why is molecular evolution important?

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.

Molecular phylogenetics often overturns oldolder theories of evolutionary relatedness:

1 Primitive kingdoms of life

Bacteria Archae-bacteria

Eukarya

Traditional: comparison ofintracellular architecture andcell wall structure.

Bacteria Archaea Eukarya

Molecular: comparison of16S rRNA sequences.

A B

2 The “New Animal Phylogeny”

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

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

http://www.zi.ku.dk/evolbiology/courses/ME04/7_9/springer200-phyl.pdfSCA 1

http://www.zi.ku.dk/evolbiology/courses/ME04/7_9/springer200-phyl.pdf

BRCA 1

Genome-wide molecular phylogenetics is ouronly hope between very closely related species:

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%

Source: Wolfgang Enard, Max-Planck-Institute of Evolutionary Anthropology, Leipzig, Germany

Where are the molecular evolutionteaching resources and information?

Unfortunately there are very few inEurope; most resources are to be

found in the USA:

http://www.ncbi.nlm.nih.gov/About/primer/phylo.html

http://www.nsta.org/

http://www.megasoftware.net/

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...

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:

http://en.wikipedia.org/wiki/Evolution_of_mammals

http://en.wikipedia.org/wiki/Molecular_phylogeny

Wikipedia also has pretty good entrieson molecular evolution...

http://www.embo.org/scisoc/teachers_wk07report.pdf

For details of the EMBO report onmolecular genetics education in Europe...