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Developmental homology and dissociation
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)
Homologous structures need not be specified by
homologous genes
(insect segmentation)
Segmentation of the Drosophila embryo
Genetic control of segmentation in Drosophila
Segment polarity genes make up the bottom level
of the regulatory hierarchy
Segment polarity genes establish boundaries between segments
and control patterning within each segment
Expression of segment polarity genes is conserved in beetles…
Cupiennius salei
The functions of en and wg in
subdividing the embryo into
segments appear to be conserved
krusty, a gap mutants in Tribolium
Pair-rule mutants in Tribolium
eve pair-rule function is conserved in beetles
Chromophore-assisted laser inactivation
ftz deletion does not affect segmentation in Tribolium
Pair-rule gene expression in Schistocerca
even-skipped expression in Lithobius
even-skipped expression in Lithobius
eve/ en
eve expression does not show two-segment periodicity
Expression of pair-rule genes in Chelicerates
primary pair-rule genes in Cupiennius
paired - secondary pair-rule in Tetranychus
Evolution of Arthropod segmentation
- Some parts of the segmentation pathway are conserved.
- There is some turnover of genes within the overall pathway
- Pair-rule patterning may be a higher insect innovation
Segmentation in long germ band insects
Q ui ck Ti m e ™ an d a P l an ar RG B de co m p re ss or ar e n ee de d t o s ee t h is pi ct u re .
- Simultaneous generation of segments
- Segmentation independent of growth
- Occurs in syncytial environment
Cellularization before blastoderm formation in
Segmentation in short germ band insects (Tribolium)
-Sequential generation of segments
-Segmentation coupled to growth
- Occurs in a cellular environment
The global patterning mechanisms cannot operate in
the same way as in Drosophila
Maternal gradient of bicoid establishes AnteriorPosterior axis in the Drosophila embryo
The roles of maternal gradients in Drosophila
Gradients form from maternally deposited transcripts
by diffusion or transport in a cell-free environment
bicoid function is conserved in Cyclorhapha
Maternal gradients in Drosophila and
RNA interference
Inhibition of Bcd protein synthesis in Megaselia results in
posterior duplication (an embryo with two butts…)
bicoid does not exist outside higher Dipterans
hunchback is a conserved component of the Anterior
determination system
RNA interference
Tribolium hunchback is correctly regulated in Drosophila
Tribolium hb
Tribolium hb transgene in Drosophila
Some maternal system must therefore exist in beetles
But how does it work without bicoid?
hunchback can substitute for bicoid
Making anterior hunchback stripe
in the absence of bicoid
In Tribolium, anterior patterning is controlled by
orthodenticle and hunchback
otd; hb
otd is deposited
Removal of otd and hb eliminates
anterior structures
A new mechanism for a new mode of development
Anterior structures
Anterior structures
A maternal protein gradient can only work in a syncytium
bcd has taken over the ancestral functions of otd and hb ?
A parasitic wasp, Copidosoma floridanum
Polyembryonic development
Polyembryonic development
Primary morula
Secondary morulae
Polyembryonic development in Copidosoma floridanum
Polyembryonic development evolved independently as an
adaptation to parasitism
Segmentation without maternal gradients
engrailed expression
in Aphidius ervi
Segmentation without pair-rule genes?
How do developmental pathways diverge from
a common ancestral state?
- By recruitment and loss of component genes
- By re-deployment of old genes in new patterns
- By changing regulatory interactions between genes
Somatic sex determination pathway in Drosophila
Sex determination is cell-autonomous (X:A ratio or dsx expression)
Somatic sex in Drosophila is controlled by a splicing cascade
Establishment (X:A ratio)
Maintenance (autoregulation)
Regulation of downstream target genes by doublesex
Yolk protein expression
Sex determination mechanisms in insects
Y-chromosomal genes (Tipulidae, Tephritidae)
Autosomal genes (Culex, Anopheles)
Mobile genes (Megaselia, Musca)
X:Autosome ratio (Drosophila)
Genotype of the mother (Chrysomia, Sciara)
Haploid/ diploid (Hymenopterans)
Environmental factors (Pseudacteon)
Sex determination in the medfly Ceratitis capitata (Tephritidae)
Sex is controlled by a maledetermining factor on the Y
Differential splicing of transformer in Ceratitis
transformer controls sexual differentiation in Ceratitis
Intersexes produced by tra RNAi
Sxl and dsx in Megaselia scalaris (Phoridae)
Sex determination in Megaselia
Megaselia lacks differentiated sex chromosomes
The Maleness factor is mobile and can be located on different chromosomes
This can create new Y chromosomes from former autosomes
Sex determination systems in Musca domestica
In male-heterogametic strains, sex is determined by a single masculinizing factor (M), which can
be located either on a Y chromosome, or on 4 different autosomes
Some female-heterogametic strains are homozygous for M, and sex is determined by a dominant
feminizing factor F
Other female-heterogametic strains lack M, and sex is determined by a recessive masculinizing
factor Fman
In arrhenogenic strains, sex of the offspring depends on the genotype of the mother
Sexually dimorphic splicing of dsx is conserved in Musca
Musca doublesex expression is sexually dimorphic
Somatic sex correlates with sexually dimorphic doublesex splicing, irrespective of
the upstream sex determination mechanism
Musca dsxF induces vitellogenin synthesis in males
Musca dsxM promotes male-specific morphology in Drosophila
Musca dsxM has the same
phenotypic effect as Drosophila
The mechanism of sex-specific
differentiation appears to be
conserved, even if the upstream
sex determination signal is not
dsx is required for the development of reproductive organs in Musca
A model for Musca sex determination?
Suppose that:
dsx produces a male-specific product by default
F is required for female-specific splicing of dsx
M represses F
F-D could be an M-insensitive allele of F
F-man could be a non-functional allele of F
Ag and tra could be leaky alleles of F or M expressed
in the germiline??
Could F be a homologue of the
Drosophila transformer gene?
doublesex controls sexual differentiation in Lepidoptera
Bombyx mori
Sex determination in Lepidoptera
In Lepidopterans, females are the heterogametic sex (males ZZ, females ZW)
W? or Z:A?
Splicing regulator
Differential splicing of dsx
Male development
Female development
Evolution of the sex determination pathway
The function of doublesex in sexual
differentiation and the sexually dimorphic
splicing of dsx are highly conserved
The immediate upstream regulator of dsx
splicing (tra) may also be conserved?
The primary sex determination signals evolve
rapidly and vary among closely
related groups
Presumably, the downstream targets of dsx are
also different in different species
How does the fly count to 2?
Sxl “measures” the X:A ratio reflected in the balance between “numerator” and
“denominator” gene products
Numerator genes are located on the X chromosome (sisA, sisB, sisC, and runt); a
single denominator element (deadpan) is located on an autosome
Sxl was recently recruited in the sex determination cascade
Sxl protein is highly conserved in all Dipterans: Musca (83%), Chrysomia, Ceratitis,
Megaselia, etc.
Sxl is spliced in a sexually dimorphic fashion in other Drosophila species (D. virilis,
D. subobscura), but not in other Dipterans (Musca, Megaselia, Ceratitis).
Dipterans outside Drosophila also lack the male-specific, translation-terminating
Although the RNA binding domain of Sxl is highly conserved, Sxl proteins from
Musca or Ceratitis cannot regulate the splicing of tra in transgenic
Sex determination mechanism based on Sxl is a Drosophila innovation
So where did the numerator elements come from?
The origin of numerator genes
The role of Sxl in sex determination is very recent, so the numerator genes must
also have acquired their functions in sex determination recently
All numerator genes have other functions in development that clearly predate
their roles in sex determination: segmentation (runt), neurogenesis (sc,
da, dpn), signaling (upd)
What does it take to be a numerator gene?
Genes must be located on the X chromosome
Must be able to regulate gene expression
Must be expressed very early in development
One of the numerator genes is scute
bHLH transcription factor with a very ancient
function as a proneural gene
Part of a gene cluster evolved by tandem
duplications (scute, achaete, l(sc))
Shares regulatory elements and overlapping
expression with achaete
Changes in scute regulation were responsible for its recruitment
in the X:A sex determination signal
Recruitment of scute for the numerator function
The duplication of achaete and scute predates the recruitment of scute as a
numerator element
In contrast to neurogenesis, achaete cannot substitute for scute in its sex
determination role
Changes in scute coding sequence were not required for the acquisition of its new
The numerator function of scute depends on specific cis-regulatory elements
Models of pathway evolution
Retrograde growth from a simple ancestral state
Component replacement
Emancipation and regrowth