2. evo-devo

• Evo-devo


  Evolutionary developmental biology
• Evolutionary relatedness of different species


  • Closely related organisms share characteristics
  • Characteristics change over generations due to natural selection and artificial selection
• Homologous structure


  Similar in structure, position and evolutionary origin (but not necessarily in function)
• The genomes of seemingly very diverse organisms retain similarity (orthologous genes)
• Human development can be modelled in other organisms, due to similarity in fundamental developmental processes
• Model organisms used in human developmental biology research

  • Bacteria
  • Yeast
  • C. elegans
  • D. melanogaster
  • D. rerio
  • X. laevis
  • M. musculus
  • Larger models e.g. sheep
  • H. sapiens
• Advantages of using model organisms

  • Conservation at the genomic level
  • Conservation of developmental processes
• As scientists, we consider the question we are asking and choose the best model with which to address it
• Many of the fundamental processes that underlie organ function, such as control of how and when cells proliferate, evolved very early during the history of multicellular life on Earth and hence have been conserved in the evolutionary pathways that have lead to organisms that appear as different as flies and humans
• Model organisms


  • Mus musculus (mouse)
  • Homo sapiens (human)
  • Gallus gallus (chicken)
  • Xenopus laevis (frog)
  • Danio rerio (zebrafish)
  • Drosophila melanogaster (fruit fly)
  • Caenorhabditis elegans (worm)
  • Saccharomyces cerevisiae (yeast)
  • Escherichia coli (bacterium)
  • Bos taurus (cow)
  • Ovis aries (sheep)
• Mus musculus (mouse)


  • Extensive similarities with all the complex physiological systems of humans
  • Develop a range of similar diseases that affect these systems, AND certain diseases not normally experienced by mice (eg cystic fibrosis) can be experimentally induced
• There are THOUSANDS of unique, well-characterised inbred strains and genetically engineered mutants of mice available in international repositories
• • Early-acting mutant phenotypes difficult to study in mice (resorbed by mother)
  • Embryonic manipulations difficult (inside mother)
  • Development and life cycle relatively slow (months)
  • Relatively expensive to maintain
  • Physiology is of a SMALL animal
  • Very strict ethics (this is a good thing!)
• Homo sapiens (human)


  • The ultimate reason we learn development from other organisms is to understand our own development
  • Many diseases, 5000 genetically based
  • Self-reporting mutants
  • Some good family pedigrees
  • Genome sequence complete
• • No experimental access to humans
  • Foetal material difficult to obtain
  • LONG generation time (~20 years)
  • Stringent ethical constraints
• Gallus gallus (chicken)


  • Incubation period of only 21 days
  • Stages of early embryonic development in humans and chicks are highly similar
• • Aristotle (384-322 BC) wrote about similarities in chick and human development - Historia Animālium
  • In the 16th Century, scientists found that chick embryos changed morphology during development - concluding that animals were not "preformed"!
• Xenopus laevis (frog)


  • Pseudotetraploid vertebrate
  • Lives in fresh water
  • Most essential cellular and molecular mechanisms are highly conserved
• • Thomas Morgan and Lancelot Hogben began the use of X. laevis as a model organism
  • Hogben discovered that when urine from pregnant women was injected into female X. laevis frogs, the frogs laid eggs (due to the presence of hCG in the urine) - fastest and most reliable pregnancy test of the 1960s!
• Danio rerio (zebrafish)


  • Around 70% of human genes have a zebrafish counterpart
  • Of the known disease-causing genes in humans, 84% have a zebrafish orthologue
  • Mutations in zebrafish genes can produce a similar phenotype to human diseases
  • Very easy to maintain large numbers
• • Zebrafish are vertebrates
  • Embryonic development occurs EXTERNALLY - ready access to, and visualisation of, embryonic development
  • Embryonic development is rapid, with major organ development within the first 36 hours
  • Can induce mutations, or test toxicity simply by adding the substances to the water!
• Drosophila melanogaster (fruit fly)

  • Very inexpensive to raise
  • Prolific breeding rate
  • Breeding age of 10 days old – ie generation times are very short
  • Large-scale multi-generational breeding experiments can be rapidly performed
• • Drosophila have a simple genome, around 1/26th size of human, and only 4 Chromosomes
  • 75% of known human disease genes have an orthologue in Drosophila
  • Drosophila are INVERTEBRATES
  • Drosophila lack blood vessels
  • Drosophila don't generate antibodies to fight disease
• Caenorhabditis elegans (worm)


  • Small – around 1mm in adult length
  • Easy to cultivate – grown on agar plates, with bacteria for food
  • Short life cycle – egg to (hermaphroditic) adult is only 3 days
• • Around 40% of genes implicated in human disease have orthologues in worms
  • C elegans used in labs today derive from a single sample found in some mushroom compost in 1950s UK
• • Brenner, Horvitz, Sulston won the 2002 Nobel Prize for discoveries concerning genetic regulation of organ development and programmed cell death
  • Mellor and Fire won the 2006 Nobel Prize for RNA interference technologies
  • Tsien, Shimomura, Chalfie won the 2008 Nobel Prize for development of Green fluorescent protein (GFP) for visualising biological structures in living organisms
• Saccharomyces cerevisiae (yeast) and Escherichia coli (bacterium) are also used as model organisms for fundamental molecular biology research
• Bos taurus (cow) and Ovis aries (sheep) are sometimes used to study aspects of developmental biology, to address the critical issue of SIZE