IB Biology Year 1 - Epigenetics

Epigenetics

• Study of how environmental conditions alter gene expression → does not change DNA sequence

• There is mounting evidence that the chemical modifications that occur to the DNA in gametes could in certain circumstances be passed on to the next generation both at the cellular level as well as whole organism level

Quorum Sensing

a form of cell-to-cell communication in bacteria where they release chemical signals to coordinate their behavior and gene expression in response to population density. Creates biofilm. These signals, called autoinducers, accumulate in the environment and trigger changes in gene expression once they reach a certain concentration.

Regulation of Gene Expression by the Environment → Epigenesis

differentiation of cell structures/functions from undifferentiated state (stem cells!) to acquire specific functions and structures. This process is influenced by epigenetic mechanisms

Epigenetic mechanisms

Biological processes that control gene expression without altering the underlying DNA sequence.

Examples:

• DNA methylation

• Histone modification

• Chromatin remodeling

• Non-coding RNAs (ncRNAs)

List some environmental factors/conditions that can affect the epigenetic status

Methionine, folic acid, vitamin B, nicotinic (produces effects of nicotine), reservatrol, high-fat diet, metal ions, nickel, etc.

Give an example of Phenotypic Plasticity based on Environment and an Example of regulating gene expression.

UV exposure increases expression of the gene that codes for the melanin protein.

Give another example of regulating gene expression:

There is substantial evidence that smoking increases the rate of DNA methylation. Mothers who smoke while pregnant have been shown to influence the methylation patterns of their unborn children too!

What does DNA methylation do?

• Alters gene expression without changing the DNA sequence itself

• Regulates gene expression by recruiting proteins involved in gene repression or by inhibiting the binding of transcription factor(s) to DNA.

What if a tumor suppressor gene is methylated?

It can be silenced, leading to unchecked cell growth and potentially contributing to cancer development

Methylation Recap

• H-group replaced by CH3 in the nitrogen bases of DNA (usually Cytosine! In promoter region)

• This methyl group is now considered an “epigenetic tag” = chemical modification that changes the expression of a gene (protein + or -)

• Most methylations repress gene expression…usually

Methylation of Histones

• DNA wraps around histones to condense

• Nucleosome is a unit of histones bound together (8)

How are air pollutants epigenetic tags?

• Shown to decrease methylation → which means things that should be turned off (like inflammation) will turn on (causing asthma)

• Indoor cooking can cause decreased methylation (increase risk of inflammation)

Regulation of Gene Expression by the Environment (think of twins)

• For some traits it can be hard to tell how much influence the environment has over gene expression

  • Comparing identical and fraternal twins can be helpful in determining that

• There is an increased percentage of identical twins sharing a trait that suggest that a genetic component contributes to the onset of the trait

• However, when the twins are younger, there are less differences in epigenetics → this can drift apart when they are older due to differing lifestyle choices or environmental exposures

What is an Epigenome?

• Sum of all epigenetic tags in cell/organism

• Tags can be passed on via mitosis

• Reprograming (wiping of tags) occurs (twice!) in formation of gametes = meiosis

Epigenetics and the environment emerging patterns and implications

• Different environment cues (such as nutrition, chemical compounds, temperature changes and other stresses) can affect phenotypes and epigenetic gene regulation in experimental model systems

• A growing number of human studies have demonstrated long-term effects as a consequence of diet, exposure to chemical components and other external factors; the effects are particularly apparent when exposure to the environmental factors occurs during gestation

Impacts of Fetal Programming?

• Early life nutritional insults (under-/over-nutrition) can lead to metabolic disorders such as obesity and diabetes by causing epigenetic changes in hypothalamic appetite regulatory genes in the fetus.

• Famine in pregnancy is shown to impact an offspring’s mental health in adulthood

Albinism

Caused by genetic mutations that disrupt melanin production. Methylation, a chemical modification to DNA, can influence gene expression but is not the direct cause of albinism.

Formation of Alleles

New alleles are formed by mutations, which are changes to the base pair sequence of the organism’s genetic code

Insertions and Deletions

• Known as “frameshifts” b/c they shift the reading frame of DNA

  • Adding a nucleotide/letter → Insertion

  • Removing a nucleotide/letter → Deletion

Substitution

One base is replaced by a different base. “Point” mutations!

3 types:

Location of Mutations: Gamete/Somatic

• If a mutation occurs in germ-line cell (one that will give rise to gametes i.e. egg or sperm cells), then this mutation can be passed to an organism’s offspring

• This means that every cell in developing embryo will carry the mutation

• As opposed to germ-line mutation, somatic mutations occur in cells found elsewhere in an organism’s body

• Such mutations are passed to daughter cells during the process of mitosis, but they are NOT passed to offspring conceived via sexual reproduction

Causes of Mutation (4 main types)

• Spontaneous: Mutation that arises spontaneous

• Physical: exposure to radiation that damages the DNA

• Chemical: exposure to chemicals (ex: heavy metal ions) that damage the DNA

• Biological: viruses that insert themselves into host DNA

Wild Type

refers to the standard “normal” allele; the non-mutated version of the gene that codes for a functional protein

Silent type

Base substitution that results in no change of the amino acid when the altered messenger RNA (mRNA) is translated

Missense

Base substitution that results in the replacement of one amino acid for another in the protein made by the gene

Nonsense

Based substitution that results in a shortened polypeptide that may function improperly or not at al

Frameshift - Insertion

A frameshift mutation shifts the grouping of the 3 bases that code for 1 amino acid; the resulting protein is usually nonfunctional

Frameshift - Deletion

A frameshift mutation shifts the grouping of the 3 bases the code for 1 amino avoid; the resulting protein is usually nonfunctional

Effect of a Mutation

Analyzing the specific change in DNA and its impact on the resulting protein, gene expression, or organismal phenotype

Mutations are more likely to be deleterious rather than beneficial when..

They occur in essential genes or coding regions, or when they affect a large number of base pairs

Beneficial mutations affect the gene pool…

Increase the frequency of specific beneficial alleles within a population's gene pool, ultimately leading to changes in the overall genetic makeup over time

If mutations are in a non-coding region…

Can disrupt regulatory mechanisms, influencing gene expression and potentially leading to disease, including cancer

Sickle cell anemia

• Homozygous sickle cell anemia or normal blood cells is not great for malaria, but heterozygous sickle cell anemia is the perfect combination

• Protist from mosquitos can’t really attach to a sickle cells → they can still do so, but it is difficult, which is why people with heterozygous sickle cell anemia get less infections than others in the population

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)

Mutation rate for viruses

• 1 in 1 billion

  • It is kept low b/c of DNA Polymerase III

  • You could increase it by smoking, radiation, extreme heat

What term best describes viruses?

Obligate molecular parasites

• Viruses are strict molecular parasites of cells

• They must infect cells and reproduce inside them

Fill in the blank:

Viruses are ___ than bacteria. Viruses ___ in size. Viruses ___ grow.

1. smaller

2. vary

3. do not

True or false:

Positive sense viral RNA is already 'ready' for translation as it would be equivalent to our human mRNA.

True!

Retroviruses…

are RNA that must be switched to DNA before viral protein synthesis can occur

Enveloped viruses can more easily infect…

…animal hosts/cells.

• The lipid envelope of animal cells, which allows for efficient entry and exit from cells, is a key factor in this preference. 

The ___ phase is the hidden, dormant part of viral reproduction, while the ___ phase is the active stage of viral reproduction, and the deadlier one, initiated by stressors.

lysogenic, lytic