Genetics exam 3 (4. epigenetics)

Epigenetics

• Study of how behaviors and environment can cause changes that affect gene expression.
• Changes can be heritable or non-heritable.
• Epigenetic changes are reversible, unlike genetic changes.
• DNA sequence are not changed, but how it's read is.
• Environmental influences affect genes and can be passed down, somewhat like Lamarck's inheritance of acquired characteristics.
• An experiment showed parental mice exposed to cherry blossom smell and electric shock conditioned a fear response.
• Progeny of these mice also exhibited a fear response to the cherry blossom smell without the shock, indicating transgenerational epigenetics.

Molecular Processes of Epigenetics

• Affects parts of the genome including DNA methylation, histone modification, and RNA molecules affecting chromatin structure and mRNA stability.
• DNA methylation typically occurs at cytosine bases.
• Histone modification can lighten or loosen histone packaging around DNA.
• The epigenome is the sum total of all epigenetic modifications.
• As time passes, even identical twins' epigenomes diverge.
• Epigenetic markers can be artificially turned off.

DNA Methylation

• Common mechanism in eukaryotes, involving methylation of cytosine to 5-methyl cytosine.
• Often found in regions with many CpG dinucleotides, often near promoters (CpG islands).
• CpG islands are typically not methylated when genes are expressed, but when methylated, they lead to heterochromatization and gene repression.
• DNA methylation is carried out by DNA methyltransferase.
• Demethylation can be artificially induced using demethylase.
• Methyl groups added to major groove.
• Methylation persists after DNA replication.
• Methylation inhibits transcription by changing the shape of the DNA's major groove, preventing binding of transcription factors and other proteins.

Histone Modifications

• Histone modifications can either repress or induce transcription, with over 100 types known.
• Most often involves positively charged tails of histone proteins.
• Acetylation reduces the charge and destabilizes chromatin structure, increasing transcription.
• Methylation of histone amino acids can either repress or induce transcription, depending on the specific amino acid.
• If histone tails are made more positive, they hold the DNA more tightly, leading to heterochromatization.
• If histone tails are made more negative, they repel from the negatively charged DNA, making it more easily transcribed.
• These mechanisms can be passed on through replication.
• Genes wrapped around histones are turned off, while genes unwrapped are turned on.

RNA Molecules

• RNA molecules mediate transcription inactivation
• Small interfering RNA (siRNA) and short non-coding RNA (sncRNA).
• X-inactivation specific transcript (Xist) is a long non-coding RNA (lncRNA) that causes formation of Barr bodies.
• During X inactivation, the Xist gene on one X chromosome is transcribed.
• Xist RNA wraps around the chromosome it was formed from, leading to DNA methylation and heterochromatization.
• Non-coding RNA and certain proteins can bind to coding RNA and break it down, stopping translation.
• Non-coding RNA can also recruit proteins to modify histones, turning genes on or off.

Experiment Showing This Is Not Lamarck's Theory

• Experiment involving 29 mice and their babies demonstrated cross fostering.
• "Mean" / inattentive (stressed previously) moms neglect their babies.
• Their babies are stressed and their genes get methylated.
• Nice & attentive (previously not stressed) moms care for their babies.
• Their babies are not stressed, and unmethylated genes are created/maintained.
• Stress status of fostered pup is related to how it was raised, not to its genetics.
• Neglected babies of inattentive moms that underwent cross-fostering showed the pups are stressed.
• Cared for babies of attentive moms showed the pups were not stressed.
• Trichostatin A (drug that helps unmethylate the gene) injected into neglected pups, babies no longer seemed stressed.
• Methylation inhibits glucocorticoid receptor genes.

Another Experiment

• Small & runty of mice were placed with Bigger, more aggressive ♀ mice.
• Runty mice were allowed to breed, babies were runty as well.
• Remove the runty ♀ mice, & their sperm was collected to inseminate larger ♀ mice, babies were "normal".
• When MOM could see the partner, the babies were runty - when prevented from seeing, offspring were no longer runty.

Parthenogenesis

• Virgin birth.
• Present in multiple animals but not in mammals.
• A 1980s study in Cambridge tried to take the nucleus of an egg placed in sperm and use that to fertilize another egg, it didn't work.
• They tried to take the nucleus of a sperm and placed in egg and used another sperm to fertilize an egg, it didn't work.
• When an egg + sperm are crossed, a mouse is born.
• Results show changes in the egg and sperm's genes for normal fertilization & gene imprinting occur.
• At fertilization, the genes are "reset" and the changes are removed: Reprogramming (Removal of almost all epigenetics except the transgenerational ones).

Genomic Imprinting

• Examples include Prader-Willi syndrome & Angelman syndrome.
• Prader-Willi is caused by inheritance of chr 15 from father.

Nutrition During Pregnancy

• A pregnant woman's nutrition during pregnancy can change the babes epigenetics.
• Some of these changes can last for decades.
• May be responsible for certain diseases
• E.g. Dutch Hunger Winter Famine (1944-1945).
• A woman who was pregnant during the famine had children who were higher risk for certain diseases, which may be caused by methylation differences due to the famine.

Reversibility & Epigenetics

• Not all epigenetic Changes are permanent
• Some epigenetic changes can be added or removed in response to environmental or behavioral change
• E.g. smoker, vs non-smoker, vs former smoker
• The LAHRR gene is generally less methylated in smokers compared to non-smokers.
• Former smokers gradually have methylated DNA for this gene again over time.
• It typically takes a really long time but it may also be possible to do so in 1 year.

Parasites & Host Unusual Example

• The ability of a parasite to induce Phenotypic changes in host to improve transmission.
• Toxoplasma gondii infects all warm-blooded animals
• Infects rats' brains.
• Causes them to be attracted to cat urine, which makes the mice easy prey for cats.
• Cats are DEFINITIVE HOST (or felines)
• Some people believe that Humans are also affected.
• People could be more susceptible to schizophrenia.
• Chimpanzees: attracted to leopards urine.