Gene Interactions & Epigenetics - Lecture 11

Question 1

What is epistasis?

Answer 1

The interaction between two or more genes that control a single phenotype

Question 2

What are the three main types of epistasis?

Answer 2

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

Question 3

What does the A gene encode for in mouse coat colour?

Answer 3

○ 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

Question 4

What does the B gene encode for in mouse coat colour?

Answer 4

○ 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

Question 5

What does C gene encode for in mouse coat colour?

Answer 5

○ 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

Question 6

What does the W gene encode for in mouse coat colour?

Answer 6

○ 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

Question 7

What is recessive epistasis?

Answer 7

Recessive allele that dominates a different allele e.g. c allele

Question 8

What is dominant epistasis?

Answer 8

Dominant allele that dominates a different allele e.g. W allele

Question 9

What is epigenetics?

Answer 9

Heritable changes in gene expression that do not involve alterations of the DNA sequence of the genome

Question 10

What is mitotic epigenetic effect?

Answer 10

○ 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

Question 11

What is meiotic epigenetic effect?

Answer 11

○ Environmental factor switches on expression of blue in oocyte
○ Expression of the blue gene persists through multiple generations
○ Rare in animals

Question 12

What is transgenerational epigenetic inheritance?

Answer 12

○ 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

Question 13

How does DNA methylation cause epigenetic effects?

Answer 13

When cytosine is methylated it turns off transcription preventing expression of a gene

Question 14

How does histone modifications cause epigenetic effects?

Answer 14

○ With DNA methylation, the chromatin structure is altered
○ Altered structure affects gene expression
○ Altered chromatin structure can be passed on to daughter cells

Question 15

What is paternal imprinting?

Answer 15

○ Paternal allele is imprinted and silenced
○ Maternal allele is expressed in embryo

Question 16

What is maternal imprinting?

Answer 16

○ Maternal allele is imprinted and silenced
○ Paternal allele is expressed in embryo

Question 17

Example of maternal imprinting: Igf2 gene

Answer 17

○ 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

Question 18

Examples of human genomic imprinting: Prader-Willi syndrome

Answer 18

○ Deletion in parental chromosome
○ Maternal genes are intact but imprinted by methylation so not expressed

Question 19

Example of human genomic imprinting: Angelman syndrome

Answer 19

○Deletion in maternal chromosome
○ Paternal UBE3A is intact but imprinted by an non-coding RNA

Question 20

How was genomic imprinting selected in evolution?

Answer 20

○ 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

Question 21

What is the theory of imprinting?

Answer 21

○ 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

Question 22

What is the observation of imprinted genes?

Answer 22

○ 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

Question 23

What happens without imprinting?

Answer 23

○ 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

Question 24

What happens with imprinting?

Answer 24

○ 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