Developmental Mechanisms of Evolutionary Change

Advanced Developmental Biology

Developmental Mechanisms of Evolutionary Change

A. "Unity of Type" and "Conditions of Existence“

B. Hox Genes: Descent with ModificationC. Homologous Pathways of DevelopmentD. Modularity: The Prerequisite for

Evolution through DevelopmentE. Developmental CorrelationF. Developmental ConstraintsG. A New Evolutionary Synthesis

"Unity of Type" and "Conditions of Existence“

1. Differences among species that allowed each species to adapt to its environment ("conditions of existence.“)

2. Adaptations were secondary, and that the "unity of type ("homologies") was critical.

*”Evolution consists of modifying embryonic organisms, not adult ones” (Metchnikoff,1891).

Descent with modification

• Unity of type= descent from common ancestor

• Conditions of existence= natural selection• *common descent- embryonic

homologies• *modification- showing how

development was altered to produce structures that enabled animals to adapt to particular condition

Avenues of approach to evolution and development

1. To find the underlying unities that link disparate groups of animals,

2. To detect those differences in development that enable species to adapt to particular environments.

The search for Urbilaterian ancestor

• Urbilaterian ancestor/ PDA (protostome-deuterostome ancestor)– Hypothetical ancestor– Had neither endoskeleton(deu.) or hard

exoskeleton( proto.)

“Paleontology without fossil”• to find homologous genes that are

performing the same functions in both a deuterostome (usually a chick or a mouse) and a protostome (generally an arthropod such as Drosophila).

• Pax6- plays a role in forming eyes in both vertebrates and invertebrates

• Tinman/Nkx2 5- involved in heart formation in deuto. and proto.

• tailless (tll) ,orthodenticle (otd) and empty spiracles (ems)/(Otx-1, Otx-2,Emx-1,Emx-2)- genes encoding for transcription factors involved in head formation

Hox Genes: Descent with Modification

• Hox genes- basis of anterior-posterior axis specification throughout the animal kingdom

• If the underlying Hox gene expression is uniform, how did the differences among the phyla emerge?– Arose from differences in how the Hox genes

are regulated and what target genes the Hox-encoded proteins regulate.

1. Changes in the Hox protein-responsive elements of downstream genes

2. Changes in Hox gene transcription patterns within a portion of the body

3. Changes in Hox gene transcription patterns between portions of the body

4. Changes in the number of Hox genes

Changes in the Hox protein-responsive elements of

downstream genes

-Changes in the genes hox proteins regulate.

Ultrabithorax gene (Ubx)-expressed in the imaginal disc of the third thoracic segment(wing or haltere are dericed)

Drosophila- Ubx downregulate several genes in the imaginal disc

Butterfly- Genes regulated in Drosophila are not regulated in butterfly

Changes in Hox gene transcription patterns within a

portion of the body

• Distal-less (Dll) gene is critical for providing the proximal-distal axis of the appendages

• Distal-less expression occurs in the cephalic and thoracic limb-forming discs, but it is excluded in the abdomen by the abdA and Ubx proteins.

• Dll (in thorax and cephalic)= limb and wing(thorax) and jaw (head) formation

• Dll inhibited by abdA and Ubx (in abdomen) = no legs will form

Changes in Hox gene transcription patterns between

portions of the bodyA. Origins of maxillipeds in crustaceans

• Antp,Ubx, and abdA are expressed in the thorax= mirror thoracic segments

• if a thoracic segment does not express Ubx and abdA, it converts its anterior locomotor limb into a feeding appendage called a maxilliped

B.Why snakes don’t have legs

Thoracic vertebrae= have ribsCervical and lumbar= no ribs*the type of vertebra produced is specified By the hox genes expressed in the somites

• the forelimb forms just anterior to the most anterior expression domain of Hoxc-6

• hoxc6 + hoxc8= thoracic vertebrae forms ribs• During early python development, Hoxc-6 is

not expressed in the absence of Hoxc-8, so the forelimbs do not form. Rather, the combination of Hoxc-6 and Hoxc-8 is expressed for most of the length of the organism, telling the vertebrae to form ribs throughout most of the body

• The hindlimb buds do begin to form in pythons, but they do not make anything more than a femur. This appears to be due to the lack of sonic hedgehog expression by the limb bud mesenchyme.

• Sonic hedgehog is needed both for the polarity of the limb and for maintenance of the apical ectodermal ridge (AER). Python hindlimb buds lack the AER.

Changes in the number of Hox genes

• Invertebrates – single hox gene complex per haploid genome.– sponges- have one or two genes in the

complex– Insects have numerous genes in the

complex• Early vertebrate- at least 4 hox gene

complex

• How does a new cell type form?-involves the duplication and divergence of

genes.Example:Dll gene originally has only one copy in

Amphioxus but have about 5-6 closely related copies in vertebrates.

The Dll homologues have found new functions in modern vertebrates;a. Expressed in mesodermb. Expressed in forebrain

• Although it remains unproven, it is possible that the new type of Distal-less gene could have caused the migratory ectodermal cells of amphioxus to evolve into neural crest cells.

Homologous Pathways of Development

• Homologous transduction pathways• They are composed of homologous

proteins arranged in a homologous manner.

• Homologous pathways form the basic infrastructure of development. The targets of these pathways may differ, however, among organisms.

1. Dorsal-Cactus PathwayDrosophila- specify dorsal-ventral polarityMammal- activate inflammatory proteinThe pathways (one in Drosophila, one in

humans) are homologous; the organs they form are not.

2. RTK pathwayDrosophila- photoreceptorMammal- epidermal cell divisionC.elegans- vulval differentiation and division

Deep homology• When homologous pathways made of

homologous parts are used for the same function in both protostomes and deuterostomes

Example:Chordin/BMP4 pathway

demonstrates that in both vertebrates and invertebrates, chordin/Short-gastrulation (Sog) inhibits the lateralizing effects of BMP4/Decapentaplegic (Dpp), thereby allowing the ectoderm protected by chordin/Sog to become the neurogenic ectoderm.

*High chordin/Sog= low BMP4/Dpp= ectoderm develop to neurogenic cell

*Low chordin/Sog= high BMP4/Dpp= ectoderm develop to epidermal cell

Modularity: The Prerequisite for Evolution through

Development• How can the development of an

embryo change when development is so finely tuned and complex?

• How can such change occur without destroying the entire organism?

Modules• Organisms are constructed of units that are coherent within

themselves and yet part of a larger unit. Thus, cells are parts of tissues, which are parts of organs, which are parts of systems, and so on.

• In development, such modules includea. morphogenetic fields (for example, those described for the

limb or eye)b. pathways (such as those mentioned above), imaginal discs, c. cell lineages (such as the inner cell mass or trophoblast),d. insect parasegments, ande. vertebrate organ rudiments. Modular units allow certain parts of the body tochange without interfering with the functions of other parts.

Fundamental principle of modularity that allows three

processes to alter development

1. Dissociation– Not all part of the embryo is connected to one

anothera. Heterochrony - shift in the relative timing of two

developmental processes from one generation to the next. In other words, one module can change its time of expression relative to the other modules of the embryo.

CAUSES1. gene mutations in the ability to induce or respond

to the hormones initiating metamorphosis2. heterochronic expression of certain genes.

b. Allometry- growth of different part at different rates

Example:Whale skull vs human skull

2. Duplication and Divergencea) duplication part of this process allows

the formation of redundant structures, b) divergence part allows these structures

to assume new roles.Example:

1. Hox genes2. TGF-β family genes, 3. MyoD family genes, and4. Globin genes 5. Duplication and divergence in the somites

that give rise to the cervical, thoracic, and lumbar vertebrae.

3. Co-option– No one structure is destined for any particular purpose– A pencil can be used for writing, but it can also be

used as a toothpick, a dagger, a hole-puncher, or a drumstick.

Example:1. Engrailed gene

• Segmentation in drosophila• Specification of neurons• Provide anterior-posterior axis

2. Enolase or alcohol dehydrogenase• Enzyme in liver• Structural crystaline protein in lens

*In other words, preexisting units can be co-opted (recruited) for new functions.

Developmental Correlation

A. Correlated Progression– changes in one part of the embryo

induce changes in another.Example:Skeletal cartilage informs the placement of

muscles, and muscles induce the placement of nerve axons. In such cases, if one structure changes, it will induce other structures to change with it.

B. Coevolution of ligand and receptor• Ligands have to fit with receptors, and they

have to be expressed at the right place and at the right time.

• Changes in the ligand must be accommodated by complementary changes in the receptor if the receptor is to function.

• If a mutation in a gene encoding ligand (or receptor) produces too great a change, it will not bind to its complementary receptor (or ligand), and development will stop. When duplications of ligand and receptor genes occur, they can diverge and acquire new functions.

Developmental Constraints

1. Physical constraints– The laws of diffusion, hydraulics, and

physical support allow only certain mechanisms of development to occur.

Example:Structural parameters and fluid dynamics

forbid the existence of 5-foot-tall mosquitoes.

2. Morphogenetic Constraints– when organisms depart from their normal

development, they do so in only a limited number of ways.

Example:– If a longer limb is favorable in a given

environment, the humerus may become elongated, but one never sees two smaller humeri joined together in tandem, although one could imagine the selective advantages that such an arrangement might have. This observation indicates a construction scheme that has certain rules.

3. Phyletic Constraints– historical restrictions based on the

genetics of an organism's development.Example:Inductive Interactions generate structurea) Notochord is vestigial in adult vertebrae

but functional in the specification of the neural tube

b) Pronephros of chick is the source of uretic bud that induuces the formation of functional kidney

Canalization and the release of developmental constraints

• Canalization (Buffer systems of development) - development appears to be buffered so that slight abnormalities of genotype or slight perturbations of the environment will not lead to the formation of abnormal phenotypes

• Not all mutations produce mutant phenotypes

Heat shock protein Hsp9

• Protein that binds to a set of signal transduction molecules that are inherently unstable.

• Provides a way to resist fluctuation due to slight mutation or environmental change

• Responsible for allowing mutations to accumulate by keeping them from being expressed until the environment changes

*transient decrease in Hsp9(damage) would uncover pre-existing genetic interaction that would produce morphological variations

A New Evolutionary Synthesis

Modern Synthesis• “evolution within a species could be

explained: Diversity within a population arose from the random production of mutations, and the environment acted to select the most fit phenotypes. “

• Those animals capable of reproducing would transmit the genes that gave them their advantage.

1. GradualismVs Punctuated Equilibrium

2. Extrapolation of microevolution to macroevolution

3. Specificity of phenotype from genotype.

*POLYPHENISM

4. Lack of genetic similarity in disparate organisms

Population GeneticsBased on gene differences in adults

competing for reproductive success

Dev.Bio. And Dev.GenHas more concern on the “arrival” of the

fittest than the survival of the fittest.

SUMMARY1. Evolution is caused by the inheritance of changes in development.

Modifications of embryonic or larval development can create new phenotypes that can then be selected.

2. Darwin's concept of "descent with modification" explained both homologies and adaptations. The similarities of structure were due to common ancestry (homology), while the modifications were due to natural selection (adaptation to the environmental circumstances).

3. The Urbilaterian ancestor can be extrapolated by looking at the developmental genes common to invertebrates and vertebrates and which perform similar functions. These include the Hox genes that specify body segments, the tinman gene that regulates heart development, the Pax6 gene that specifies those regions able to form eyes, and the genes that instruct head and tail formation.

4. Changes in the targets of Hox genes can alter what the Hox genes specify. The Ubx protein, for instance, specifies halteres in flies and hindwings in butterflies.

5. Changes of Hox gene expression within a region can alter the structures formed by that region. For instance, changes in the expression of Ubx and abdA in insects regulate the production of prolegs in the abdominal segments of the larvae.

6. Changes in Hox gene expression between body regions can alter the structures formed by that region. In crustaceans, different Hox expression patterns enable the body to have or to lack maxillipeds on its thoracic segments.

7. Changes in Hox gene expression are correlated with the limbless phenotypes in snakes.

8. Changes in Hox gene number may allow Hox genes to take on new functions. Large changes the numbers of Hox genes correlate with major transitions in evolution.

9. Duplications of genes may also enable these genes to become expressed in new places. The formation of new cell types may result from duplicated genes whose regulation has diverged.

10. In addition to structures being homologous, developmental pathways can be homologous. Here, one has homologous proteins organized in homologous ways. These pathways can be used for different developmental phenomena in different organisms and within the same organism.

11. Deep homology results when the homologous pathway is utilized for the same function in greatly diverged organisms. The instructions for forming the central nervous system and for forming limbs are possible examples of deep homology.

12. Modularity allows for parts of the embryo to change without affecting other parts.

13. The dissociation of one module from another is shown by heterochrony (changing in the timing of the development of one region with respect to another) and by allometry (when different parts of the organism grow at different rates).

14. Allometry can create new structures (such as the pocket gopher cheek pouch) by crossing a threshold.

15. Duplication and divergence are important mechanisms of evolution. On the gene level, the Hox genes, the Distal-less genes, the MyoD genes, and many other gene families started as single genes. The diverged members can assume different functions.

16. Co-option (recruitment) of existing genes and pathways for new functions is a fundamental mechanism for creating new phenotypes. One such recruitment is the limb development pathway being used to form eyespots in butterfly wings.

17. Developmental modules can include several tissue types such that correlated progression occurs. here, a change in one portion of the module causes changes in the other portions. When skeletal bones change, the nerves and muscles serving them also change.

18. Tissue interactions have to be conserved, and if one component changes, the other must. If a ligand changes, its receptor must change. Reproductive isolation may result from changes in sperm or egg proteins.

19. Developmental constraints prevent certain phenotypes from occurring. Such restraints may be physical (no rotating limbs), morphogenetic (no middle finger smaller than its neighbors), or phyletic (no neural tube without a notochord).

20. The Hsp90 protein enables cells to accumulate genes that would otherwise give abnormal phenotypes. When the organisms are stressed during development, these phenotypes can emerge.

21. The merging of the population genetics model of evolution with the developmental genetics model of evolution is creating a new evolutionary synthesis that can account for macroevolutionary as well as microevolutionary phenomena.