WEEK 1, DAY 2
PHENOTYPIC PLASTICITY
IMSS BIOLOGY ~ SUMMER 2013
PHENOTYPIC PLASTICITY
Genotypes produce different phenotypes in
response to different environmental
conditions.
commons.wikimedia.org
GENOTYPE, THE ENVIRONMENT, & PHENOTYPE
KEY POINTS RE. PHENOTYPIC PLASTICITY
•
Plasticity may be expressed at behavioral, biochemical,
physiological, or developmental levels with different
degrees of reversibility.
•
Not always adaptive—some traits are plastic because of
the physiology, biochemistry, or developmental biology of
the organism.
•
Type & degree of plasticity specific to individual traits and
environmental conditions, e.g. a given trait is plastic in
response to temperature, other traits are not.
•
There is abundant genetic variation for plastic responses
in natural populations—makes possible evolution of
plasticity by natural selection (and other mechanisms).
WHICH GENOTYPE SHOWS THE LEAST AMOUNT
OF PHENOTYPIC PLASTICITY?
(A) Genotype 1
(B) Genotype 2
(C) Genotype 3
(D) They are all
equivalent.
Explain your answer.
An example of genotypic reaction norms illustrating the concept of phenotypic plasticity.
Pigliucci M et al. J Exp Biol 2006;209:2362-2367
©2006 by The Company of Biologists Ltd
Environmental changes induce differential
expression of genes.
Our understanding of how environmentinduced expression plasticity is growing.
AT WHICH STAGE IS GENE EXPRESSION
REGULATED?
(A)
(B)
(E)
(C)
(D)
REGULATION OF GENE EXPRESSION
•
Regulation of expression can occur at any stage in the
DNA-mRNA-protein pathway
REGULATION OF GENE EXPRESSION
•
Modification of DNA may up or down regulate gene
expression, e.g. chemical modification (“chemical tags”)
of DNA, which includes
•
•
DNA methylation – common mode of gene
silencing; abnormal methylation patterns are
involved in oncogenesis.
Histone acetylation – allows transcription to
proceed; histone deacetylation works with DNA
methylation in gene silencing; also, signals DNA to
be packed more densely, thus lowering gene
expression.
CHEMICAL
TAG
CHROMOSOME
METHYL GROUP
DNA
HISTONE TAIL
GENE
HISTONE TAIL
DNA accessible, gene turned on
HISTONE
DNA hidden, gene turned off
Epigenomic Marks. The epigenome can mark DNA in t wo ways, both of which play a role in turning genes off or on. The first occurs when certain chemical tags called
methyl groups attach to the backbone of a DNA molecule .The second occurs when a variety of chemical tags attach t o the tails of hist ones, which are spool-like proteins
that package DNA neatly into chromosomes.This action affects how tightly DNA is w ound around the hist ones.
•
When gene is tightly wound around deactylated histones
and highly methylated, gene expression is low.
•
When gene is loosely wound around acetylated histones
and unmethylated, gene expression is high.
•
Gene control simulation:
http://learn.genetics.utah.edu/content/epigenetics/control/
ACTIVITY: DNA AND HISTONE MODEL
• DNA is coiled around histones.
• Tightly coiled DNA is inaccessible to gene
reading machinery.
• Methyl molecules bind to DNA and block
access to genes.
• Acetyl molecules bind to histones and
increase access to genes.
• View video tutorial
http://teach.genetics.utah.edu/content/epigenetics/
DNA METHYLATION
•
Stably alters gene expression as cells divide and
differentiate from embryonic stem cells  specific
tissues.
•
DNA methylation typically removed during zygote
formation (“reprogramming”), then re-established
through successive cell divisions during development.
•
DNA methylation suppresses expression of harmful DNA
sequences that have been incorporated over time (e.g.,
from retroviral genes).
•
Involved in oncogenesis/carcinogenesis.
•
Involved in genomic imprinting.
GENOMIC IMPRINTING
•
Gene expression occurs
in parent-of-origin way
•
Imprinted alleles are
silenced such that genes
are either expressed only
from non-imprinted
allele from the mother or
father
•
Demonstrated in insects,
mammals, flowering
plants (in mammals, ca.
1% of genes are
imprinted).
EPIGENETICS OVERVIEW
http://learn.genetics.utah.edu/content/epigenetics/intro/
THE EPIGENOME
• Includes all the information, other than DNA
sequence itself, that is heritable during cell
division.
• While DNA sequences remain essentially
unchanged throughout the lifetime of an organism,
the epigenome changes immensely in response to
internal or external environmental cues.
THE EPIGENOME
•
Far-reaching impact
http://systemsbio.ucsd.edu/
EPIGENETIC INHERITANCE
• Epigenetic “tags” present on parents’
epigenomes are passed down to offspring.
• Evidence is growing for transgenerational
epigenetic inheritance, though mechanisms
are not necessarily straightforward.
• Some examples…
TOADFLAX (LINARIA VULGARIS)
•
Wildtype and peloric variant are genetically
identical—one epigenetic mutation has caused the
difference in petal shape. This epimutation is
passed on to offspring.
WILD RADISH
•
Caterpillar attack of radish plants can generate
defense phenotypes (distasteful chemicals and
protective spines) that can last for multiple
generations, even in absence of caterpillars.
•
Involves DNA
methylation, histone
modifications, and
small RNAs.
WATER FLEA (DAPHNIA)
•
Female Daphnia respond
to chemical signals from
predators by growing
protective helmets.
•
Offspring of helmeted
Daphnia also born with
helmets, even in absence
of predator signals.
•
Effect continues to next
generation, although
helmet size decreases.
http://www.nature.com/nature/journal/v401/n6748/fig_tab
/401060a0_F2.html
LAB RATS
•
Fungicide vinclozolin is used on crops, e.g. grapes.
Feeding vinclozolin to pregnant rats causes lifelong
epigenetic changes in pups. As adults, male
offpsring have low sperm counts, poor fertility,
and several diseases (prostate and kidney disease).
Persists over multiple generations.
•
Found abnormally hi
levels of methyl tags in
sperm.
DES IN HUMANS
•
•
Diethylstilbestrol (synthetic
estrogen) was drug given to
pregnant women to prevent
miscarriages during mid-20th C
but discontinued because it
caused rare vaginal cancer.
Also associated with increased
risk of breast and reproductive
cancers in daughters (and sons)
and maternal granddaughters.
http://diethylstilbestrol.co.uk/
Studies in mice suggest DES causes abnormal
methylation of genes involved in uterine development;
abnormalities present across multiple generations.
NUTRITION AND THE EPIGENOME
•
The role of diet as an environmental factor in
epigenetic change is area of active research.
•
Nutrients from
food are turned
into methyl
groups (along a
metabolic
pathway) that
are ultimately
attached to
DNA.
•
Diets high in methyl-donating nutrients can rapidly
alter gene expressions, especially during early
development when epigenome is first being
established.
•
http://learn.genetics.utah.edu/content/epigenetic
s/nutrition/
ACTIVITY: YOUR ENVIRONMENT, YOUR
GENOME
• Factors from your environment, such as diet,
physical activity, and stress level, influence
the epigenome.
IMPORTANCE OF MOM’S DIET
•
Growing evidence for
influence of mother’s diet
on offspring’s epigenome.
•
Agouti gene in mammals:
•
•
•
Unmethylated yellow
fur, obese, prone to
diabetes & cancer
Methylated brown, thin,
low disease risk
When pregnant yellow
mice fed methyl-rich
diet pups were brown,
thin, healthy for life
ENOUGH ABOUT MOM, HOW ABOUT DAD?
•
Norbotten, Sweden – a small farming
village with meticulous agricultural
records back to 19th C.
•
Lars Bygren (1980s) uses the records to
see how much food was available to
parents and grandparents when they
were kids.
•
Discovered that famine/low food
availability for paternal grandfathers
when they were 9-12 yo associated with
extended lifespan in grandchildren; early
death associated with diabetes or heart
disease in grandchildren of grandfathers
who “gorged” themselves.
THE ROYAL DIET
•
Royal jelly is complex, protein-rich
substance secreted from head glands of
worker bees.
•
The larva destined to be queen is fed lots
of royal jelly inside a “queen cup.”
•
All larvae genetically identical but royal
jelly diet silences Dnmt3 gene which codes
for enzyme involved in genome-wide
silencing.
•
•
When Dnmt3 gene is active, queen genes
epigenetically silenced and larvae
become workers.
When royal jelly turns off Dnmt3 gene,
queen genes are active and larva turns
into queen.
ROLE OF ENVIRONMENTAL POLLUTANTS
•
Increasing evidence shows the negative impact of
environmental pollutants on the epigenome, e.g. BPA
•
Pregnant yellow agouti females fed BPA  more yellow,
unhealthy babies
•
BPA-exposed moms fed
methyl-rich diet 
offspring predominantly
brown (nutrient
supplementation
counteracted negative
effects of BPA exposure)
ENTERTAINING SUMMARY OF EPIGENETICS
http://youtu.be/kp1bZEUgqVI
REFERENCES/RESOURCES
• Learn Genetics from University of Utah
http://learn.genetics.utah.edu/content/epigenetics
/inheritance/
• National Human Genome Research Institute
http://www.genome.gov/27532724
• NOVA ScienceNOW
http://www.pbs.org/wgbh/nova/education/activiti
es/3411_02_nsn.html
QUICK WRITE REFLECTION – EXIT TICKET
• What information and/or ideas from today’s
presentation, activities, resources, or
discussion did you find the most
helpful/useful? In what context (e.g., own
knowledge, dissemination to students)?
Photo by Michael Skelton