AGRC2001 - You are what your grandma ate

Inheritance refers to the transmission of phenotypic characteristics from parents to offspring, leading to relatives resembling each other.
Genetics is based on DNA sequence, a unique string of A's, T's, G's, and C's present in every cell.
Within an individual, the DNA sequence is identical in all somatic cells (muscle, liver, gut, brain).
Gametes have variable DNA due to meiosis, making each sperm's haploid DNA unique and consequential to the offspring's phenotype.

Epigenetics involves reversible alterations to chemical tags (marks) on DNA or histone proteins, not the DNA sequence itself.
These tags can be added or removed, affecting gene expression.
CpG methylation and histone acetylation are examples of such modifications.
Modern screens analyze CpG methylation across the genome.
Enzymes like DNA methyltransferases and histone acetylases catalyze these processes.
Chemical tags influence gene expression by controlling access to DNA promoter regions, with closed chromatin structures hindering gene activation.

Epigenetics raises the possibility that the environment can impact inheritance through chemical tags.
This idea revisits the debate between Darwinian (natural selection) and Lamarckian (inheritance of acquired characteristics) perspectives.
Lamarck believed that traits acquired during a parent's lifetime could be passed on, while Darwin believed inheritance was based on predispositions.
The modern understanding of genetics aligns more with Darwin's view.

Epigenetic tags can survive mitosis (cell division) and sometimes meiosis (gamete formation).
Survival through mitosis allows propagation within tissues.
Survival through meiosis could lead to the inheritance of chemical tags, impacting gene expression based on parental lifestyle choices.
Convincing examples of epigenetic inheritance are rare.
The in utero environment can affect the baby through nutrient availability and biochemistry without epigenetic mechanisms.
Emma Whitelaw's work demonstrated epigenetic inheritance in mice coat color (Agouti phenotype), where maternal diet influenced DNA methylation at the Agouti gene's promoter.
Supplementation with methyl donors during pregnancy increased methylation, resulting in darker coats and lower obesity risk in offspring.

Most events in our lives are not passed on to offspring.
The inheritance system protects gametes from insults applied to the soma (UV irradiation, physical damage).
Epigenetic marks are erased during gametogenesis, and the genome is largely demethylated after fertilization.
This ensures totipotency, allowing cells to form all tissues.

Epigenetic phenomena play a role in gene expression on a within-individual basis, working with Transcription Factors (TFs).
Transcription Factors are more critical in the gene regulatory network, as their induction is necessary and sufficient for cell differentiation (e.g., MyOD1 for muscle cell production).
Epigenetic modifiers can induce phenotypes like heart and bone hypertrophy, but are not sufficient for differentiation.

Epigenetics is implicated in parent-of-origin effects, such as differences between mules and hinnies.
The Callipyge sheep breed demonstrates polar overdominance, where heterozygote offspring only express the phenotype when the mutant allele comes from the sire.

Eating a balanced diet is crucial for health.
Vitamin C deficiency leads to scurvy.
Dietary protein provides amino acids for protein synthesis, including essential amino acids like lysine and methionine.
Methyl group synthesis requires nutrients from both plants (folate) and animals (B12).

Maternal undernourishment during pregnancy can restrict nutrients to the developing baby.
Alcohol, caffeine, and other bioactives can have predictable consequences.
Lactation is a pressure point, as compounds ingested by the mother can transfer to the infant through breast milk.

The statement that "you are what your grandma ate" is contentious.
It suggests that grandparental environmental exposure can lead to phenotypic consequences in grandchildren.
Some epidemiological evidence exists (e.g., the Dutch famine and childhood predisposition to obesity, inter-generational methylation status of IGF2).
Controlled experimental data is less available.