R15 Evo-Devo

Question 1

What is a cis-acting element ?

Answer 1

a region of DNA or RNA that regulates the expression of a gene located on the same molecule of DNA

Usually enhancers, silencers or promoters

TATA box is an example of this

A single gene may have multiple copies of cis-elements

Question 2

Case 1 of cis acting elements is ?

Answer 2

Case 1: multiple binding sites bound by the same transcription factor, includes:
- independent TF binding, each TF can bind without affecting others, the graph shows that increasing TF concentration increasing the binding (there is non threshold)
- cooperative binding: binding of one TF stabilises the binding of another, shown by a sigmoidal graph where transcription is switch on with a rapid increase

Question 3

Case 2 of cis acting elements is ?

Answer 3

Cis-acting elements are bound by different transcription factors, the combination of different TFs regulate gene expression

combinational control: only a specific combination will activate the gene

Question 4

What is a trans-acting element ?

Answer 4

a molecule, usually a protein, that regulates the expression of a gene located on a different DNA molecule or on a distant part of the same DNA molecule

Question 5

What else can developmental genes code for other than transcription factors ?

Answer 5

cell-cell signalling pathways

• Ligands released by one cell diffuse and bind to receptors of another
• Signal transduction causes a cascade in the receiving cell
• Output often changes the gene expression due to activation of TFs

Question 6

What are the 5 main signals to growing a drosophilia ?

Answer 6

• Expression of one set of genes at a time
• Genes encode for TFs or signalling components
• Domain of expression gets progressively more restricted (shown by the impacts of mutations), genes earlier on have a broader effect
• Maternal-effect genes (mRNA deposited in the egg by the mother) and zygotic genes (genes of the individual)

Question 7

What is the maternal (bicoid) effect ?

Answer 7

• Bicoid is a TF, diffuses from anterior where the mRNA is deposited by the mother then, causing a concentration gradient along the organism of transcription factors
• Cells in early stages contain the same cytoplasm allowing for diffusion of Bicoid

Question 8

What are gap genes ? especially hunchback ?

Answer 8

• Hunchback is a gap genes, contain cis-elements that have different arrangement of binding sites with different affinities for Bicoid
• Lower affinity – require higher concentration of Bicoid – for activation
• This is called positional information

Question 9

What is pair rule genes ?

Answer 9

• Pair rule genes expressed in 7 stripes along the embryo.
• Distinct enhancers controlled by different transcription factors like case 2
• These enhancers respond to specific local concentration of TFs, no other enhancer will experience the same concentration of upstream transcription factors, so no two stripes will have the same proportion

Question 10

What is segment polarity genes ?

Answer 10

14 stripes, regulated by transcription factors from the pair rule genes

Question 11

What are homeotic genes ?

Answer 11

determine identity of repeated body units, not their formation
- 8 hox genes in fruit flies, clustered in 2 gene complexes (they all share the dna domain and transcription factor binding site)
- Order of the hox genes in the complexes are correlated to the order of the body regions

Question 12

What is meant by the genetic ‘toolkit’ of development ?

Answer 12

• Set of genes controlling identity/formation/number of body parts and organization of the primary body axes
• Most operate at more than one time and place
• One tool can do a wide range of tasks

Question 13

How are genetic toolkits conserved ?

Answer 13

• Hox clusters control development in most animals
• Sequence similarity indicates a strong selection pressure to maintain function
• Higher number of duplications but same arrangement
• 4 hox genes arose by duplication of entire hox complexes in vertebrate ancestors.

Question 14

How do cis-elements evolve ?

Answer 14

Changes to enhancer sequences via mutations can result in gain or losses of a particular trait
- Darker pigmentation in wings in fruit flies
- Mutation in enhancer = new TF binding = higher expression = darker colour
- Expression driven from other enhancers in other regions unaffected

Co-option: use of a pre-existing gene for a new function
- One gene may code for a trait and regulate another gene due to changes in cis-elements
- Entire new genetic pathways have been co-opted in evolution

Pelvic morphology in stickleback fish
- Mutation in pelvic enhancer = TF no longer binds = no pelvic expression = no spines
- Different selection pressures cause this difference in expression

Question 15

How does altering regulatory elements rather than protein code have an advantage ?

Answer 15

• Mutations in gene coding sequences would affect expression in all tissues
• Many processes might be affected (pleiotropy)
• Biochemical function also (potentially) altered
• Potential negative consequences for fitness = problematic
• Alterations in cis-regulatory elements have more specific impacts
• Changing one aspect of the expression of protein while preserving expression in other developmental processes
• Less constrained = route for evolution

Question 16

How do trans-elements evolve ?

Answer 16

• Changing TF expression or binding ability
• Addition or alterations of amino acid motifs that can then interact with new proteins
• Pre-existing function retained; new function just added
• Forms new interacting combinations of TF modules and cis-regulatory modules.

Question 17

What is meant by developmental constraints ?

Answer 17

not all phenotypes are observed in nature
- Multiple causes: lack of genetic variation, lack of pathways, strong correlations among traits
- TFs binding to multiple genes produce pleiotropy
- Constraints can limit “evolvability”

Question 18

What are 4 main categorise that control development ?

Answer 18

• Receptors, diffusible signals (ligands), enhancers, repressors.

Question 19

What are some examples of a mutant in hox genes, segment polarity genes, pair rule genes, gap genes, maternal-effect genes in drosophilia ?

Answer 19

Hox genes – legs instead of antennae
Segment polarity genes – more segments affected
Pair rule genes – no two segments are the same size
Gap genes – missing of domains (missing of segments)
Maternal-effect genes – one end is correct, the diffusion gradient setup by the mother

Question 20

What is the order of gene activation during development

Answer 20

maternal effect –> gap genes –> pair-rule genes –> segment polarity genes

Question 21

What is meant by syncytial ?

Answer 21

Cells are joined by one cytoplasm to allow for diffusion of TFs

Cellularisation is the process in which this cytoplasm is removed

Question 22

How can a homeotic mutant gained a function ?

Answer 22

function if expression where gene is not normally expressed, from transcriptional activator, expression in head = extra pair of legs

Question 23

How is segmentation regulated ?

Answer 23

Other segments repress segments that aren’t meant to be there, e.g., the tail of a fly is repressing genes for wings
- Mutants have a problem with repressing this

Question 24

What are some examples of changing the trans and cis-elements in drosophilia and their effects ?

Answer 24

Changes in trans-regulation of elongation genes. TF now also expressed in sepals so structures grow.

Changes in cis- (sequences of enhancer) regulation of the pigmentation genes

Question 25

What is meant by environmental plasticity ?

Answer 25

One genotype can produce different phenotypes in response to environmental stimuli

Question 26

Which of these statements correctly describes an aspect of binding cooperativity? It is enabled by physical interactions between cis-regulatory elements It creates shallow gradients of gene expression It is a property displayed by some maternal effect genes It involves a single binding site

Answer 26

It is a property displayed by some maternal effect genes TRUE: we saw the example of Bicoid regulating the Hunchback gap gene