WEEK 1, PART 3MORE 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/nutrig-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.

Genotype Environment (external &

internal)

Phenotype

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%2F10.1371%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.