Descent with modification: Application to the evolution of development
Homologous characters are derived (with modification) from a common ancestral character
Both structure and function of homologous traits are evolving away from the ancestral trait
The concept of homology can be applied to developmental mechanisms and the genes that control them
We need to identify homologous developmental pathways in divergent taxa, and to trace the evolution of their organization and function
Three levels of homology in developmentHomologous genes?
Homologous structures?Homologous developmental processes?
Homeotic mutants in Drosophila
Homeosis is a replacement of a body part with another, apparently normal body part (W. Bateson, 1894)
In Drosophila, homeotic mutants re-specify “segment identity”
HOX genes and axial patterning- Transcription factors with a highly conserved DNA-binding domain (the “homeobox”)
- Regulate expression of distinct sets (?) of target genes
- Expressed in distinct but usually overlapping domains along the anterior-posterior body axis in all Metazoans
- Organized in (usually) uninterrupted clusters
- The order of genes in the HOX cluster is (usually) the same as the order of their expression domains along the AP axis (collinearity)
The homeobox is a highly conserved DNA-binding domain
DrosophilaAmphioxusMouseHumanChickFrogFugu
Zebrafish
HOX4 homeodomain
HOX genes control axial patterning in all Metazoans
Axial patterning in the vertebrate brain
Evolution of HOX clusters in Bilateria
Evolution of tandem gene clusters
Gene duplication by unequal crossing-over
Divergence of coding and regulatory sequences
The complement of HOX genes continues to evolve
Evolution of HOX clusters in vertebrates
Mouse
Fugu
Zebrafish
- Vertebrates have multiple HOX clusters
- Paralogous HOX genes may have partly redundant functions
- Some genes and clusters become specialized for distinct functions
- Different lineages lose some genes and acquire new functions for others
New HOX genes for new segmental morphologies?
Ed Lewis'es model 1978
The entire HOX cluster pre-dates Arthropod radiation
HOX genes and the Proximo-Distal axis of the vertebrate limb
HOX genes acquire new functions
HOX gene expression boundary coincides with a morphological transition
HOX gene expression boundary coincides with a morphological transition
HOX gene expression boundary coincides with a morphological transition
HOX domain boundary coincides with a morphological transition
- Segment homology can be traced across all Crustaceans
- Segment and appendage morphology is highly variable in Crustacea
- HOX expression domain in different Crustaceans are NOT homologous
- The boundaries of HOX domains often coincide with morphological transitions
HOX domain boundaries and morphological transitions
Thorax/ Abdomen
Gnathal/ Thoracic
Poison claw/ walking legs
Stalk/ opisthosoma
?
Hindlimb
HoxC6 and the cervical/ thoracic boundary
The number of cervical metameres is different, but the Hoxc6 always marks the cervical/ thoracic boundary
Stellate ganglia - a novel structure
Combinatorial code?
HOX genes in a highly modified organism
Brachial crown
All Metazoans possess homologous HOX clusters
Individual HOX genes are highly conserved
HOX genes control A-P axial patterning in all Metazoans
The role of HOX genes in axial patterning is a Metazoan (or at least Bilaterian) synapomorphy
The complement of HOX genes is different in different taxa
Orthologous HOX genes are not always expressed in homologous domains
Orthologous HOX genes do not always specify homologous structures
HOX genes are not linked to specific morphologies or cell types; rather, they provide abstract spatial information
HOX genes may be recruited for new functions in structures that have no homologs in other taxa
Descent…
… with modification
What allows the HOX genes to retain their ancient strategic function, and yet have a different specific role in each context?
Hox genes act by regulating multiple target genes
Ubx- regulated
HOX genes specify abstract spatial information
Ubx provides the distinction between the forewing and the hindwing in all insects - but this distinction is different in each case
HOX genes regulate the expression of multiple target genes
Different HOX genes have distinct (but sometimes overlapping) sets of downstream targets
These sets of target genes change during evolution, leading to changes in HOX gene functions and to acquisition of new roles
The expression of HOX genes in distinct axial domains serves as the conserved backbone of a developmental mechanism, while the more peripheral aspects of that mechanism continuously evolve
We still know very little about the downstream targets of the HOX genes
The more things change, the more they stay the same
HOX genes and developmental homology
- HOX clusters are homologous across Metazoa
- The Anterior-Posterior body axis is also homologous in all Metazoa
- Specification of regional domains along the AP axis by HOX genes is a homologous developmental mechanism in all animals in which it is found
However, these three levels of homology are dissociable and to a large extent independent
Homologous genes
HOX genes Axial patterningey/ Pax6 Eye developmentDll/ Dlx Appendage developmentcd/ Cdx Hindgutotd/ Otx Anterior brain
dpp/ TGFhh/ Shhwg/ WntNotch
Transcription factors/ selectors
Signaling pathways
The functions of Notch signaling
Drosophila
Bristle developmentDorso-ventral patterning
in the wingOmmatidial cell fatesLeg joint formationA-P patterning of larval
epithelium
Vertebrates
Neuronal and glial cell development
Auditory hair cellsSomitogenesisT lymphocyte fatesLeft-right asymmetryChondroblast specificationPatterning feather primordia
There are many more signaling events that there are signaling pathways!
The functions of HOX genes
Drosophila Vertebrates
A-P patterning of:ectodermCNSmusclesvisceral mesoderm
A-P patterning of somitesand CNS
P-D axis of the limbsReproductive tractHair follicle development
Homologous genes often function in non-homologousstructures.
Engrailed functions in Drosophila segmentation
engrailed expression in Arthropods
Flea Cricket Crustacean
engrailed & Wnt expression in Annelids
Helobdella Platynereis
A common origin of segmentation in Protostomes?
Was the last common Bilaterian ancestor segmented?
Amphioxus neurula
A closer look at segmentation in the leech
- In early development, en is only expressed in a few clones in each segment-At later stages, segmental stripes form by cell rearrangement-The cells that express en in the segmental stripes are not always clonally related to the early en-expressing cells- This suggests that en is not required for segmentation, but acts after the segments are already established
Phylogenetic distribution of segmentation
Segmented ancestor is very unlikely…
Distal-less specifies distal appendage fates in Drosophila
Dll also specifies distal appendage fate in spiders
dac staining
RNAi
Lobopodia and parapodia
Onychophoran
Polychaete
Legs, tube feet and ampullae
Mouse
Ascidian
Sea urchin
Homologous developmental pathway for Proximo-Distal axis specification?
eyeless/ Pax6: a “master regulatory gene” for eye development
Photoreceptive neuronsFrontal eye precursor cellsPigment spot
Amphioxus
Pax6 expression in the presumptive eye field
Mouse
PhotoreceptorsLensIrisCorneaOlfactory epithelium
Pax6 in the Cephalopod eye
eyeless/ Pax6 expression in diverse Metazoans
Gene Drosophila Vertebrates Flatworms
Otd/ Otx Photoreceptor cells Neural retina Photoreceptor cells
ey/ Pax6 Eye imaginal disc Lens placode, Photoreceptor andoptic vesicle pigmented eye cells
toy Eye imaginal disc
So/ Six3 Eye imaginal disc, Eye precursor andphotoreceptor cells, photoreceptor cellsoptic lobes
Optix/ Six6 Eye imaginal disc Optic vesicle,neural retina,retinal epithelium
Rx Retinal cells
Opsin Photoreceptor cells Photoreceptors Photoreceptor cells
Conservation of the eye regulatory network
Eye evolution from a common ancestral organ?
Vertebrate Arthropod Cephalopod Arcoid
Differences in eye structure between animal phyla
Similar adult organs, but radically different development
Some differences between vertebrate and arthropod eyes
Vertebrates Arthropods
Optics Single front element Compound
Origin of CNS Epidermisphotoreceptors
Orientation of Inverse Eversephotoreceptors
Photoreceptor Ciliary Microvillarstructure
Secondary cGMP ITPmessenger
Mechanism of Membrane Membranelight detection hyperpolarization depolarization
Developmental homology and dissociation. Part I.
Homologous genes need not function in the development of homologous structures(HOX genes, Notch signaling)
Expression of a homologous gene does not imply that developmental pathways are also homologous(engrailed and metamerism)
Homologous developmental pathways may control the development of non-homologous structures(Dll in appendages, Pax6 in the eyes)
Segmentation of the Drosophila embryo
Genetic control of segmentation in Drosophila
Pair-rule gene expression in grasshopper
eve
ftz
Drosophila Tribolium
Developmental homology and dissociation. Part II.
Homologous genes need not function in the development of homologous structures
Expression of a homologous gene does not imply that developmental pathways are also homologous
Homologous developmental pathways may control the development of non-homologous structures
Homologous structures need not be specified by homologous genes (insect segmentation)