BIOL 4010 Lecture Notes - Lecture 16: Variant Surface Glycoprotein, Small Interfering Rna, Rna Interference
2 May 2018
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Plasticity: From Genes to Generations
Levels of Plasticity:
• Genotypic
• Physiological
• Morphological
• Behavioural
• Life history
Genotypic Plasticity:
• Plasticity in the structure and function of genetic architecture
• Epigenetics:
o Changes in gene expression without a change in gene sequence
o "change in phenotype without change in genotype"
o Previously…
• Lamark - driven by need
• Darwin - driven by selection
o Waddington: Epigenetic Landscape
• Depends on what the marble interacts with in the environment
• Ex. Exposing fruit flies to ether --> duplicated thorax
▪ Mutant flies did not have a change in the genome, all still genetically identical
while changing morphological structure
• How to get heritable change without changing gene sequences?
o Position effect variegation
• Differential gene silencing due to rearrangement or transposition of gene location with
heterochromatin
• Change in gene position has effect on gene expression
▪ Gene sequence remains unchanged
• Recall: Chromatin = condensed form of DNA
▪ DNA is wrapped around histone proteins to create nucleosomes --> "beads on a
string"
▪ Heterochromatin: tightly bundles, DNA unexposed
• --> "turned off"
• Polymerase can’t access DNA
• No gene expression
▪ Euchromatin: loosely bundles, DNA exposed
• --> "turned on"
• Polymerase can access DNA
• Gene expression
• Case Study: Trypanosoma brucei
▪ Parasitic kinetoplastid
• Causes trypanosomiasis (sleeping sickness)
• Occupy blood of host organism
• Results in cyclic occurrence and absence of fever, joint, pain and itching in
blood phase
▪ Immune system targets surface proteins on T. brucei and begins to amount an
immune response
• Just when the immune system is ready to act, the surface proteins change
• Due to Vsg gene = variant surface glycoprotein (1000s variants within
genome)
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• Physical movement of these genes into and out of heterochromatin
determines expression and which surface proteins are produced
(during interphase of mitosis)
• *see slide
▪ Key point: trypanosome active genotype changes plasticity in response to host
immune system, without changes to DNA sequence, to improve success in its
environment = adaptive plasticity
o RNA interference
• Inhibition of gene expression or gene translation through interference of mRNA
molecules using other RNA molecules
▪ Also known as post-transcriptional gene silencing (PTGS)
• miRNA (micro RNA) and siRNA (small interfering RNA)
▪ Small non-coding RNAs (20-25 bp long)
▪ Can be endogenous or exogenous
▪ Recruit enzymatic complexes which slice mRNA with complementary sequences
to miRNA/siRNA fragment
• Sliced mRNA does not get translated into protein
• Case Study: Scarabaeid Beetles
▪ Regulation of development in insects
▪ Use of RNAi to induce formation of ectotopic organs, functional compound eyes
▪ Organ development and RNAi:
• Used RNAi to silence orthodenticle (otd), a homeobox gene involved in
head development
• Homobox genes: regulate batters of morphogenesis, "master regulators"
(ex. Hox genes)
▪ Silencing otd induced ectopic eyes to develop that externally resemble compound
eyes
• Ectopic eyes developed lens, rods/cones, and associated neural tissues
• Developed underlying optic nerve-like structures
• Transcriptional activity at location of ectopic eyes converges to activity of
regular compound eyes (respond to light)
• Respond behaviourally to light-aversion when wild-type eyes are
surgically removed
• Key point: by interfering one gene, induced formation of a highly complex and
functional organ in a novel location
▪ Flexibility and modularity of development of complex structures, even with
major regulatory perturbations
▪ System for exploring evolution of the development of complex structures using
endogenous mechanisms
o DNA methylation
• Addition of a methyl group (CH3) to a cytosine or adenine within DNA molecules,
which induces the formation of densely packed heterochromatin
• Usually at or upstream of gene promoter
▪ Occurs at "CPG" islands within the genome
• CpG = cytosine - phosphate - guanine
▪ Potential to pre-program offspring to be better adapted to current environments
• = "environmental matching" hypothesis
• Ex. Stress level and behaviour of mother rats regulates DNA methylation of offspring
▪ Behavioural change by mom influences state of methylation at glucocorticoid
receptors
▪ Amount of maternal care is influenced by stress levels
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