WEEK 1 DAY 2 PHENOTYPIC PLASTICITY IMSS BIOLOGY

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 Phenotype Genotype Environment (external & internal)

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) (C) (D) (E)

REGULATION OF GENE EXPRESSION • Regulation of expression can occur at any stage in the DNA-m. RNA-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.

• 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/v 401/n 6748/fig_ta b/401060 a 0_F 2. 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-20 th 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 19 th C. • Lars Bygren (1980 s) 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 Dnmt 3 gene which codes for enzyme involved in genome-wide silencing. • • When Dnmt 3 gene is active, queen genes epigenetically silenced and larvae become workers. When royal jelly turns off Dnmt 3 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/kp 1 b. ZEUgq. VI

REFERENCES/RESOURCES • Learn Genetics from University of Utah http: //learn. genetics. utah. edu/content/epigenetic s/inheritance/ • National Human Genome Research Institute http: //www. genome. gov/27532724 • NOVA Science. NOW 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