R15 Evo-Devo Flashcards
What is a cis-acting element ?
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
Case 1 of cis acting elements is ?
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
Case 2 of cis acting elements is ?
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
What is a trans-acting element ?
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
What else can developmental genes code for other than transcription factors ?
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
What are the 5 main signals to growing a drosophilia ?
- 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)
What is the maternal (bicoid) effect ?
- 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
What are gap genes ? especially hunchback ?
- 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
What is pair rule genes ?
- 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
What is segment polarity genes ?
14 stripes, regulated by transcription factors from the pair rule genes
What are homeotic genes ?
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
What is meant by the genetic ‘toolkit’ of development ?
- 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
How are genetic toolkits conserved ?
- 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.
How do cis-elements evolve ?
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
How does altering regulatory elements rather than protein code have an advantage ?
- 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
How do trans-elements evolve ?
- 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.
What is meant by developmental constraints ?
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”
What are 4 main categorise that control development ?
- Receptors, diffusible signals (ligands), enhancers, repressors.
What are some examples of a mutant in hox genes, segment polarity genes, pair rule genes, gap genes, maternal-effect genes in drosophilia ?
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
What is the order of gene activation during development
maternal effect –> gap genes –> pair-rule genes –> segment polarity genes
What is meant by syncytial ?
Cells are joined by one cytoplasm to allow for diffusion of TFs
Cellularisation is the process in which this cytoplasm is removed
How can a homeotic mutant gained a function ?
function if expression where gene is not normally expressed, from transcriptional activator, expression in head = extra pair of legs
How is segmentation regulated ?
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
What are some examples of changing the trans and cis-elements in drosophilia and their effects ?
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
What is meant by environmental plasticity ?
One genotype can produce different phenotypes in response to environmental stimuli
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
It is a property displayed by some maternal effect genes
TRUE: we saw the example of Bicoid regulating the Hunchback gap gene
