Animal Development & Evolution Flashcards
Ur bilateria?
common ancestor of all bilateria
3 main branches of bilateria?
Deuterostomes
proteostomes:
-ecdysozoa
-lophotrochozoa (annelida, mollusca, platyhelminthes)
ur metazoa?
ancestor of all metazoans (Ur bilateri + non bilateria metazoans)
how do differences in animal structures arise in development?
structure develops due to differences in GENE EXPRESSION/TRANSCRIPTION
e.g. 4 cell stage embryo:
one cell behaves differently from others
- INTRACELLULAR SIGNALLING:
contains certain molecule that others dont that will affect cell behaviour (TFs)
(HOX genes etc…) - INTERCELLULAR SIGNALLING
interaction between cells that determine cell differntiation outcome - cell signals neighbour(s)
e.g. like zpa in developing limb patterning digits across A-P axis)
pathways are complex, but just a few of them (Hedgehog, wingless,fgf, bmp)
these pathways work together in different embryonic development stages
(e.g. one cell expresses one TF, causes it to secrete intercellular signal molecule, influences TF expression in other cell)
TF families in metazoa
most TF families found in all metazoans
meaning
1.most signalling systems are very ancient - evolved in common ancestors and retained in all descendents as they diverged away from each other - traces back to original metazoan
- whats giving rise to diversity between different groups of animals is HOW this shared toolkit of systems is being used
control of gene transcription in eukaryotes?
Cis regulatory elements CREs on chromosome upstream of gene
enhancer - will contain elements that regulate that gene
TFs bind recognition sites on enhancer
will have +ve or -ve effect on transcription
(activator vs inhibitor)
transcription unit - DNA length RNA polymerase will run across to give mRNA transcript
receptor on plasma membrane
signal binds it (e.g. Hh)
signalling cascade from receptor kicked off
activates previously inactive TF in the cell
active TF then binds enhancer
has repressive/activation effect
activation effect may be enough to start trasncription of that gene
signal out of cell leads to internal change in expression
sorts of mutation that can change gene activity
mutation in regulatory region
(affects how/when/where gene is expressed)
mutation in coding region
(affects the action of expressed protein)
coding changes effect
in intron - silent - probably no effect
in coding/exon:
may produce change in protein (codon code??)
-then MAY be significant to affect its function (e.g. TF ability to bind site)
-proteins pleiotropic - one changed protein may affect many different pathways
lots of change likely to be deleterious
regulatory changes effect
will only affect how TFs affect the trasncription of THAT specific gene
hypothesised that mutations in regulatory region are more constricted in their effect than coding region changes
argued that this sort of mutation then may be more viable - so more likely to lead to adaptation (no adaptation when deleterious/inviable)
stickleback pelvis example
add to notes
3 spined stickleback has pelvic spines
marine populations of species have full pelvis and spines
some freshwater lake populations have reduced pelvis and pelvic spines
(MAYBE more advantageous die to different conditions and predators)
used linkage mapping to find that difference is in the Pitx gene (encodes a TF)
has 30kb enhancer
3kb coding region
NO DIFFERENCE IN CODING REGION sequence in spined and spineless pops
no difference in TF itself most likely
BUT big differnce in where it is transcribed in embryo
Pitx1 staining showed:
in developing jaw of both populations
in pelvis of spined marine pops
BUT NOT in pelvis of lake fish
DIFFERENCE is in WHERE it is being transcribed in embryo
narrowed down sequence difference to ~500b
enhancer now called PEL
took that PEL enhancer and coupled it to GFP
GFP on in pelvis of marine fish
so in marine fish PEL turns on Pitx1 in pelvis
causes spines to be developed there
took marine PEL and put it next to Pitx1 coding region
put this constricted gene inyo genome of lake fish which normally spineless pelvis
restores spine development in the FW fish
sequenced the chromosome pitx1 is on in many pops of stickleback
found deletion in 500bp region that would be PEL enhancer
all of the different pelvis spine reduced pops had deletions here
proof of strong selection in lake populaiotns too
-reduced heterozygosity
may have driven spine loss whatever advantage that conferred
drosophila male wing spots example
(add to notes)
some drosophila species males have wing spots
some species’ males dont
male wing spots restricted to certain part of dros phylogeny
single point of origin
(individual species in other part in obscura group has a different pattern of wingspot - different origination)
development of spot:
Yellow gene encodes enzyme in melanin synthesis
gain and loss of an enhancer of this determined spot presence (a species in the spot part lost spots -lost this Yellow enhancer
(simpler spot?)
in D. elegans - SPOT enhancer of Yellow
responds to distal-less (activator)
and engrailed (repressor)
distal-less expressed in distal wing region
so Yellow expressed in distal wing part - distal wing spots
in posterior of wing engrailed is expressed - inhibits Yellow
expression of both causes anterior spot on distal part of wing
(d tristis from obscira family’s spot is controlled by different factors doing same thing)
D. guttifera has different (complex) pattern of spots
can use reporter to see where Yellow gene is active
Yellow expression lines up with spots
also lines up with Wingless (TF) expression
different wingspot patterns via Yellow reacting to expression of different TF signalling pathways in different species
differing promoters the reason
evolution of COMPLEX spot patterns in drosophila
(add to notes)
in d. melanogaster - no complex spots - just melanation around veins in wing
no complex expression pattern
no spots
(No VS, no complex wingless expression pattern)
then having complex wingless expression pattern evolved
AND evolution of novel VS enhancer - complex pattern of it evolved
led to development of complex wingspot patterns
evolution of complex wing spots:
-largely due to changes in gene regulation (not coding sequence changes)
-changes to specific regulatory elements in pathways of genes to change their function differently in different regions in development
bithorax mutation in drosophila?
WT
-wing on T2 - T2 legs…
-haltere on T3 - T3 legs…
bithorax:
T2 and T3 segments both look like T2
segment T3 has been transformed into T2
HOX gene family
gene family (homeotic?????)
NON- identical genes that arose from process duplications of another gene within the family
related by sequence (v similar)
all encode TFs
each gene produces slightly different HOX TF
physically close
in drosophila - side by side on chromosome
order of HOX genes on chromosome corresponds to order that they are expressed/pattern the A-P axis
transcription of Ubx and Distal-less in drosophila
turned on 3hrs into development
at 6hr stage of embryo:
Ubx from T3 segment (patchily) then strongly through rest of abdomen (abdomen is legless)
means that whole part of A-P axis is exposed to Ubx TF
early distal-less expression is important for developing structures that will become legs(ventral)/wings(dorsal)
can’t turn on in abdominal segments as Ubx strongly expressed in abdomen (reason why insects have no legs on abdomen)
can turn on in T1/T2 cause no Ubx
(guessing weaker Ubx in T3 allows distal-less to come on a bit - T3 identiy)
drosophila HOX gene expression and segments
different Hox genes have different anterior limits to their expression (corresponde to location on chromosome)
so different developing segments will experience different combinations of HOX TFs along the A-P axis
leads to segment identity
e.g. T3 forming halteres and T3 legs
while T2 forms wings and T2 legs
HOX gene expression pattern in other arthropods
insect v crustacean
very similar HOX gene transcription pattern as in drosophila (anterior limits, same HOX A-limit order)
SAME HOX genes expressed in same order alon A-P axis
KO of same HOX genes gives very similar mutations (e.g. legs in wrong places.,.)
HOX gene mechanism holds up through arthropod phylum
vertebrate HOX gene families
mice have an orthologous family of HOX genes to drosophila (not identical but close enough to have arisen by duplication)
Mouse HOX family maps relatively close to drosophila one
BUT:
-5’ gene duplications of the family to produce more genes
vertebrates have 4 HOX families on different chromosomes among genome
so WHOLESALE rounds of chromosome duplication to get multiple chromosomes with similar HOX genes
-NONE of the families have all of the memebers
B only missing one
ACD a bit sparser
so after chromosome duplication there has been loss of HOX genes from the families
(ig cause redundancy from same member on other chromo)
also vertebrate HOX families are more tightly clustered - side by side w no other genes in between them (unlike drosophila)
mouse HOX gene expression pattern
expressed in early embryo at certain parts of A-P axis
staggered along axis
(similar to arthropods)
-Hox9 - anterior border before CNS
expressed from lumbar posteriorly behind the thorax (not in thorax)
-Hox1,4,9 expressed with different anterior borders - in same order as on chromosome
co-linear expression (localised expression too)
also expressed with temporal arrangement as well as spatial
-more anterior ones are expressed earlier in development
KO of all Hox9s in mouse?
Hox9 expressed in lumbar area posteriorly
helps pattern that area
so when removed that patterning is disrupted
lumbar vertebrae transformed into thoracic vertebrae
localised expression of HOX gene gives rise to local expression of TF - gives rise to segment identity
novel functions of HOX genes in vertebrates
some have been recruited for novel function:
to pattern different structures apart from A-P identity
A and D 9-13 (a has 9 only) used to pattern limb buds later in development
annelida (proxy for lophotrocozoa?) HOX expression
similar to others
HOX conserved from ancestor of deuterostomes, lophotrocozoa, and ecdysozoa
staggered in chromosomal order
differences inn HOX expression drives difference in different segments
HOX function in animal evolution?
add to notes
most phyla have conserved this ancestral patterning function of HOX genes
however a few have changed it:
-nematodes have lost some HOX genes that are found in others
-remaining HOX genes have been dispersed across genome on different chromosomes with a lot of DNA between them
-HOX genes have lost control over A-P axis
-HOX mechanism broken up for some adaptive reason
also seen in other groups:
echinoderms have regained radial symmetry (despite being in bilateria)
HOX genes in echinoderms - different patterns of HOX loss and also differences in trasncription - no longer have role in patterning major A-P axis
also molluscs -
different members of group have differnces in body axis
(torsion in gastropoda, A-P/D-V axis changes in cephalopoda)
differences in HOX gene systems could correlate to different changes in anatomy and axis patterning
HOX patterning - more ancient than Ur-bilateria?
add to notes
metazoans that diverged earlier than Ur-bilateria:
Cnidaria (porifera has no HOX genes)
in cnidaria:
recognisable orthologs of HOX genes found
(much less similar to each other within cnidaria than in bilateria tho -cause split off earlier - more time to diverge from each other)
so hox genes and how they function is older than Ur-Bilateria
cnidarian HOX genes?
add to notes
have HOX genes with similarity in finction to A-P patterning ones in bilateria
(not side by side in genome tho - dispersed)
similar patterning in cnidaria
-e.g. pattern the Oral-Aboral axis
relationship between aprticular HOX expression and identity of that end of body
also
have role in patterning 2’ axis too (with bmp)
(axis perpendicular to O-Ab)
so hox genes and how they function is older than Ur-Bilateria
Changes in HOX gene expression to give differences in morphology in arthropods
2 aspects:
spatial control of HOX gene expression itself (how is Ubx turned on in that specific chunk - how can it be modified and changed in different arthropods?)
how does the HOX product control specific target genes (e.g. Ubx in specific chunk repressing distal-less in insect abdomens to get no legs)
Hox genes and caterpillar prolegs:
most insects: 3 pairs of THORACIC legs (due to Ubx repression of distal-less in abdomen)
however some differ somewhat
Lepidopteran larvae (esp Bttrfly larvae) have prolegs on 4 abdominal segments (A3-6)
not identical in anatomy but have claws and can move/rotate
also develop much the same as thoracic legs including need for distal-less to be expressed there early in development
BUT Ubx is present in abdomen so how distal-less for proleg development?
in butterfly embryos
% complete embryo:
20%:
Ubx on strongly throughout whole abdomen
distalless only in head and thorax regions
25%:
in A3-6 - there are small regions where Ubx has been cleared or switched off
40%:
distal-less is turned on in these small Ubx free regions - causes development of prolegs there
Hypothesis:
relationship between Ubx and distal-less hasn’t changed (still represses)
however an UNKNOWN mechanism exists to clear/switch off Ubx in sections of A3-6
allowing distal-less expression and development of prolegs on A segments
