Gene Interactions & Epigenetics - Lecture 11 Flashcards
What is epistasis?
The interaction between two or more genes that control a single phenotype
What are the three main types of epistasis?
One mutation affects the phenotype of another mutation:
○ Reveals how cascade of biochemical reactions are sequentially organised e.g. signalling pathways
Either mutation present no phenotype, but the double mutant has a phenotype:
○ Reveals buffering mechanisms that prevent phenotypic manifestations e.g. cancers
Either mutation have the same phenotype but the double mutant a different phenotype
○ Reveals prevailing mechanisms that alter phenotypic manifestations e.g. dominant alleles
What does the A gene encode for in mouse coat colour?
○ A encodes for agouti signalling protein (ASP1)
○ Melaoncytes produce eumelanin (dark) and pheomelanin (yellowish)
○ When ASP binds to Mc1R (on melanocytes) it inhibits the pathway which leads to the production of pheomelanin
○ Aa or AA is agouti; aa is black
What does the B gene encode for in mouse coat colour?
○ B Encodes for Tyrp1 and is important to produce eumelanin
○ b is a mutation which produces a less active Tryp1
○ Bb or BB is agouti; bb is brown
What does C gene encode for in mouse coat colour?
○ C encodes for an essential tyrosinase to produce melanin
○ c mutation produces a nonfunctional tyrosinase enzyme so no melanin is produced
○ CC or Cc is agouti; cc is albino
What does the W gene encode for in mouse coat colour?
○ W encodes for the kit protein - a type of tyrosine kinase receptor
○ Kit is essential for survival and migration of melanoblasts
○ W allele is dominant white spotting; ww is wild type
What is recessive epistasis?
Recessive allele that dominates a different allele e.g. c allele
What is dominant epistasis?
Dominant allele that dominates a different allele e.g. W allele
What is epigenetics?
Heritable changes in gene expression that do not involve alterations of the DNA sequence of the genome
What is mitotic epigenetic effect?
○ Environmental factor switches on expression of red and green genes in a somatic cell
○ Expression of green gene is transient and is not expressed in daughter cells
○ Expression of the red gene persists through multiple cell divisions
What is meiotic epigenetic effect?
○ Environmental factor switches on expression of blue in oocyte
○ Expression of the blue gene persists through multiple generations
○ Rare in animals
What is transgenerational epigenetic inheritance?
○ Pregnant woman is exposed to an environmental factor e.g. toxins
○ Fetus (F1) could be influenced
○ Reproductive cells in fetus (F2) could also be influenced
How does DNA methylation cause epigenetic effects?
When cytosine is methylated it turns off transcription preventing expression of a gene
How does histone modifications cause epigenetic effects?
○ With DNA methylation, the chromatin structure is altered
○ Altered structure affects gene expression
○ Altered chromatin structure can be passed on to daughter cells
What is paternal imprinting?
○ Paternal allele is imprinted and silenced
○ Maternal allele is expressed in embryo
What is maternal imprinting?
○ Maternal allele is imprinted and silenced
○ Paternal allele is expressed in embryo
Example of maternal imprinting: Igf2 gene
○ Igf2 gene is required for normal growth
○ Maternal copy of the gene is imprinted and silenced
○ Paternal copy is expressed
○ In a mouse with a mutant maternal allele: normal growth
○ In a mouth with a mutant paternal allele: dwarf
Examples of human genomic imprinting: Prader-Willi syndrome
○ Deletion in parental chromosome
○ Maternal genes are intact but imprinted by methylation so not expressed
Example of human genomic imprinting: Angelman syndrome
○Deletion in maternal chromosome
○ Paternal UBE3A is intact but imprinted by an non-coding RNA
How was genomic imprinting selected in evolution?
○ Affects a limited number of genes (~80 in humans)
○ Many imprinted genes involved in foetal growth
Pattern observed is:
○ Paternally expressed genes promote growth
○ Maternally expressed genes suppress growth
What is the theory of imprinting?
○ Haig and Westoby (1989)
○ Imprinting evolved due to conflicts between maternal and paternal genomes over the allocation of maternal resources to offspring
○ This creates a “tug-of-war” between maternal and paternal alleles, leading to asymmetry in gene expression
What is the observation of imprinted genes?
○ Imprinted genes are involved in growth and metabolism
○ Paternal imprinting: mitigates against the production of larger offspring
○ Maternal imprinting: mitigates against the production of smaller offspring
○ This sets up an epigenetic battle between parental interests
What happens without imprinting?
○ An embryo may acquire more resources than its fair share, growing faster and increasing its fitness
○ This reduces resources available to its siblings, negatively affecting their success
What happens with imprinting?
○ Imprinting establishes an evolutionary balance in resource acquisition
○ This balance reflects a trade-off between:
- The benefits of resource acquisition for one embryo
- The costs to the inclusive fitness of its siblings
○ The balance differs for maternal and paternal alleles due to their differing evolutionary interests
