Transcript here - IMSS Biology 2014

WEEK 1, PART 3
MORE ON GENETICS & THE ENVIRONMENT
IMSS BIOLOGY ~ SUMMER 2013
ENVIRONMENTAL IMPACT
(DIRECT GENE EFFECTS)
•
Gene expression (how the
organism develops and
functions) can be influenced
by the external world and
the internal milieu (e.g.
hormones, metabolic
products) of the organism.
•
We discussed how this can
happen by way of the
epigenome, but it can also
happen when the
environmental stimulus
interacts directly with the
genetic machinery, e.g. by
way of direct gene
activation  protein
expression.
OBESOGENS
•
Environmental pollutants that are endocrine disrupting chemicals,
which negatively affect metabolic balance at many physiological
levels (adipose tissue, liver, pancreas, brain) and thus promote
obesity.
•
Actions
•
•
•
Changes basal metabolic rate
Causes release of insulin which favors energy storage
Alters hormonal control of appetite and satiety centers in the brain
• Mechanisms
• Direct gene activation
• Epigenetic actions
PHARMACOEPIGENETICS
•
Research on the role of epigenetics in drug response and toxicity
has taken off contributing to understanding of epigenetic influence
on drug metabolism and response (which account for individual
variation in drug responses.
•
Increasing numbers of pharmaceuticals shown to cause persistent
epigenetic changes—longer term exposures lead to more
permanent modifications to DNA modification and histone
acetylation, e.g.,
•
•
•
hydralazine (for hi BP, vasodilator) inhibits DNA methylation
isotretinoin (for cystic acne) interferes with normal transcription
factor activity at gene promoters
Epigenetic side effects of pharmaceuticals implicated in
development of everything horrible you can think of (heart disease,
cancer, neurological disorders, cognitive disorders, obesity,
diabetes, infertility, sexual dysfunction)
http://www.medicinabiomolecular.com.br/biblioteca/pdfs/Nutrigenomica/nut
rig-0043.pdf
REVISITING THE CONNECTION: EVOLUTIONARY GENETICS
•
The environment can modify genotype expression (many levels of
regulation, epigenetic factors).
•
The environment can modify phenotypes from development to
death (phenotypic plasticity).
•
Thus, phenotypic variation in populations (that which natural
selection acts on) is a consequence of the heritable components of
the variation (genome & epigenome) AND the specific environment
that has modified them.
Let’s think in this moment about climate—
the rapidity of climate change.
Starting with temperature.
How even small changes in temperature can result in…
…MAJOR GENETIC CHANGES WITH MACROEVOLUTIONARY
CONSEQUENCES
•
Many species have genotypic sex determination - sex determined
by sex chromosomes at fertilization, e.g. mammals, birds.
•
Some species have environmental sex determination – sex
phenotype determined by environmental cue, e.g., nutrient
availability, temperature; e.g. some reptiles (crocodilians, sea
turtles, some lizards), some fish
TEMPERATURE SEX DETERMINATION
•
Observation: farm-raised fishes tended to be males – farmers raised
larvae in warmer waters to accelerate growth.
•
Researchers from Barcelona (Navarro-Martin et al. 2011) found
mechanism that links temperature and gonadal sex in European Sea
Bass
•
Increased T increases DNA methylation of gonadal aromatase
promoter (CYP 19a) in females—silencing enzyme that converts
androgens to estrogens, so that genetic females develop as males.
•
Few degrees rise in temperate  phenotypic masculinization 
 impacts on population dynamics.
•
Relevant in context of global warming.
http://www.plosgenetics.org/article/info%3Adoi%2F
10.1371%2Fjournal.pgen.1002447
Three friends were arguing about what would
happen to a population of sea turtles as a result of
climate warming. This is what they said:
Jason: “I think the population will increase,
because all metabolic processes (like growth and
reproduction) will increase with rising
temperature.”
Jeff: “I think the numbers of males in the
population will increase, because the warmer
environment will favor males over females.”
Danika: “I think the population will decline,
because the numbers of fertilized eggs will
plummet.”
Which person do you most agree with and why? Explain your ideas.