Hox, ParaHox, NK: Germ Layers And Tail In Animal Evolution Flashcards
Big “transitions” in the history of animal life
- Origin of life (replicators)
- Origin of cells
- Eukaryagenesis
- Origin of multicellularity
- Origin of bilaterians
Bilaterians
- Lophotrochozoa
- Ecdysozoa
- Deuterostomia
Bilaterian characteristics
- bilateral symmetry
- A-> P axis (brain and sense organs)
- centralised nerve cord and co-ordination
- muscle blocks each side
- “through-gut”; mouth and anus
3D exploration
- burrowing
- nutrient mixing
Evo-Devo @ bilaterian origin challenges;
1) large suite of changes
2) stem lineage
3) deep time (540-555Mya)
Predictions ?
- single genetic change : NOH
- new genes (maybe)
- rewiring existing GRNs (probably…)
How to study deep time
- Hypothesis-free; looking for new genes, compare gen- / proteo-omes of non-bilaterians and bilaterians
- Hypothesis-guided
New genes? Analysis
Compare:
- 36 bilaterans
- 8 non-bilaterians
- 18 non-animals
New genes? Finding
- 1580 new genes
- zero retained by all
New genes? Update.
- 102 genomes
- 1699 new genes
- 0 retained by all
- more work needed to resolve what they do
Hypothesis guided
Genes involved in
1) AP pattern
2) through-gut (mouth and anus)
3) mesoderm (muscle)
4) nerve cord
Genes involved in AP patterning
- Hox
- what tissue type?
Drosophila
- ectoderm (cuticle, nerve cord)
- mesoderm
C. elegans
- ectoderm
- mesoderm
- endoderm (transient)
Mus
- Ectoderm (nerve cord, neural crest)
- mesoderm (somites, visceral organs)
Amphioxus
Ectoderm (epidermis, nerve cord)
Tunicates
Ectoderm
Were Hox genes recruited or rewired to pattern ectoderm?
Good q
Mesoderm and through gut
- patterned by other, Hox-like Homeobox clusters
Homeobox
> 200 (shown by idiogram)
Gene classes
- ANTP
- PRD
Clustered ANTP: NK
- in Drosophila: 6 genes (180kb)
- 4 sets due to WGD + loss
- re-arranged across chromosomes
- a bit broken up in chordates
- understudied
tinman
- in Drosophila
- has duplicated vertebrate orthologs
- LOF mutant: no heart
- expressed in vertebrate developing heart (mesoderm)
Drosophila heart
- Pulsatile muscular vesicle that pumps haemolymph around the body
- mesodermal structure
NKX2.5 KO
- Heart defect in mus
- human mutations: congenital heart disease
All NK cluster homeobox genes are involved in
- mesoderm
- but not A-> P
- cross-sectionally
Some NK cluster homeobox genes are
Expressed in nerve tissue; extra function
What about endoderm (gut) + lining?
- another gene classes? ANTPs?
ParaHox
- ANTP homeobox cluster (in some animals)
- discovered in Amphioxus (Pdx)
- Gsx, Pdx, Cdx
- humans: Chr13
- 3 other cluster remnants; gene loss!!
Pdx
- expressed in middle of gut in Amphioxus
- lost in insects
- present in some Ecdysozoa
- expressed in pancreas/duodenum (Mus, humans)
- Mus mutation = pancreas absent, gut defect
- human mutations = diabetes predisposition
Cdx
- aka Chordal
- a lil bit into nerve cord
- Amphioxus, Drosophila, frog: end of gut/anus
Cdx KO expts
- difficult in Amphioxus
- anus does not break through
- larval explosion
3 homeobox gene clusters
- Co-opted to pattern 3 germ layers
- allows bilatera to evolve
- due to duplication
Gsx
- not expressed in mouth in Amphioxus, vertebrates or Drosophila
- Amphioxus, Drosophila: expressed in brain (data from more species needed)
Gibula
- trochophore mollusc (marine snail)
- expressed in embryo stomadium (mouth)
- and brain
- ancestral situation has been modified in different lineages?
Where did these genes come from,
And when? They are not bilaterial
Hox + ParaHox
- Bilateria
- Cnidaria
Hox + ParaHox + NK
- bilateria
- Cnidaria
- sponges
Homeobox evolution
1) ANTP class expanded thru much duplication
2) in bilateria, 3x clusters held as “islands”; others dispersed
3) recruitment (other genes and GRN: also key)
Fox Class TFs
- recruited for Bilaterian mesodermal patterning
- lots! Early duplication
- Drosophila, honeybee, sea urchins, H. sapiens
Can evolution bring unrelated genes into a cluster to create a functional unit under common control, to start patterning new structures?
1) compare genome sequences
2) look for micro-synteny
Microsynteny
Genes consistently found together, despite all the shuffling
Pharyngeal gene cluster in Deuterostomes
- Nkx2.1, Nkx2.2, Pax1/9, Foxa1 all expressed in same region
