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Chapter 20

HMB265H1 Chapter Notes - Chapter 20: Pleiotropy, Cell Surface Receptor, Arthropod Eye


Department
Human Biology
Course Code
HMB265H1
Professor
Maria Papaconstantinou
Chapter
20

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HMB265 Lecture 20 READINGS - Developmental Genetics
Pg 577-583, 593-606
Genes direct cellular behaviours underlying development
- Not all genes turned on in all tissues
- Cells regulate expression of genes so each gene’s protein product appears only when
and where it’s needed
17.1 Model Organisms: Prototypes for Developmental Genetics
- Each model organism’s genome completely sequenced
- Easier to identify genes whose mutant alleles have phenotypic effects on development
All living forms are related
- Cells of all eukaryotic organisms have common structural features (nucleus +
mitochondria)
- Similar metabolic pathways
- EX: Eyes of insects + vertebrates evolved from same pathway
Yet all species are unique
- But also differences
Nematodes vs Humans
- At 2 cell-embryo stage
- If nematode loses 1 cell, can’t develop b/c both cells already differentiated
- If human embryo loses 1 cell, will get identical twins b/c human embryo can “regulate”
fates according to their environment
- EX: Make up for missing cells\
17.2 Mutagenesis Screens
What genes required for development?
- Need to do a mutant screen
- Examine mutant organisms, identify rare individuals w/ phenotype of interest
- EX: find all the individuals w/ bad eyes
Genetic screens identify genes required for specific developmental processes
- Molecular mechanisms that guide development of fruit fly compound eye
- Compound eye has 800 ommatidia
- Each one made of small number of cells that assemble in same order every time
- If have defect will be iterated 800 times in each eye = easy to see mutant
- First cells to assemble in each ommatidium = 8 photoreceptors
- Last of these 8 photoreceptors to assemble = R7
- R7 contains rhodopsin = flies can detect UV light
- In mutant flies, eyes missing R7 (has all the other photoreceptors except for R7)
- = now have screened and identified interesting mutants
- = have a bunch of flies that we know are mutated
Separating mutations into complementation groups
Now need to determine number of different mutant genes represented in collection
- Do this by sorting mutations into complementation groups
- Each group contains different mutant alleles of same gene
- (one gene can be mutated in diff ways)
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- Did many pairwise crosses between flies that led to offspring having no R7
- Mutations resolved into 2 complementation groups (genes)
- = loss of R7 gene arises from mutation in 2 possible genes
- Sevenless (sev)
- Bride-of-sevenless (boss)
Mutant gene identification
- Have genome sequence for each model organism = easy to identify genes causing
mutant phenotypes
- EX: sev and boss strains have point mutations
- Chemical mutations alter single nucleotide pair
- Mutations mapped using chromosomes containing deletions w/ molecularly
defined breakpoints
- Don’t want to identify the wrong gene as cause of mutation
- Can verify gene assignment
- Add back transgenic copy of WT gene to mutant organism see if get WT
organism
- Or mutagenize candidate gene in WT to see if get mutant
Clues from the nature of the encoded protein
= now have identified gene important for developmental process
- Want to find out about molecular nature of process
- Use amino acid sequence of protein encoded by gene
Sev and Boss genes controlling fly eye:
- Both proteins have hydrophobic domains
- = likely proteins have to go through cell membrane = likely found a surface of certain
cells
- Sev = transmembrane receptor protein present on surface of R7 precursor cells
- Boss = transmembrane ligand found on R8 surface
- When R7 precursor contacts R8, Boss protein binds with Sev
- Initiates signal transduction cascade resulting in expression of genes that determines R7
cell fate
Primary mutant screens can miss key genes
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- Can identify genes dedicated to particular developmental pathway
- = products of many genes cooperate to produce outcome
- But usually hard to recover mutations in genes that encode important pathway
components hard to get in primary screen
The problem of pleiotropic or redundant genes
- Interaction of Sev and Boss at surface of cells initiate series of events
- Influences expression of other genes in nucleus of R7 cell
In mutation screen for absence of R7, why didn’t find mutations in other genes due to problems
with Sev and Boss?
- Missed those genes in screen b/c they were pleiotropic:
- = b/c they’re required for more than one developmental pathway (not just R7
specification)
- Many of these genes needed for Drosophila viability
- If gene function lacking, organism dies before can look at its eyes
- Mutations in redundant genes
- - Also missed in screens for morphological phenotypes (no R7)
- If 2 genes do same thing, losing one doesn’t result in mutant phenotype
= pleiotropic + redundant genes make it hard to identify other genes whose products involved in
signaling cascade
Dominant modifiers of sensitized mutant phenotypes
- Can try to identify pleiotropic genes using modifier screen
17.5 A Comprehensive example: Body-Plan Development in
Drosophila
- Studies on genetic control of basic body plan of Drosophila
- How fly’s body becomes differentiated + specialized along anterior-posterior axis (h2t)
- People look at how fertilized Drosophila egg becomes embryo w/ defined segments
- Get head, thorax, abdomen
How does animal develop the right number of segments?
How does each body segment “know” what kinds of structures to form?
- Maternal-effect genes
- Early in development before transcription starts, have maternal-effect genes at
play
- genes encode maternal components (supplied by egg and enable embryo dev’t)
- Products deposited into eggs
- Establishes regional differences in embryo
- Zygotic segmentation genes
- Large group of genes expressed in zygote’s own genome
- Subdivides body into identical body segments
- Homeotic genes
- Set of genes that encode transcription factors
- Assigns identity to each body segment
= 3 things:
- Maternal-effect genes
- Zygotic segmentation genes
find more resources at oneclass.com
find more resources at oneclass.com
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