14
Genes, Development, and
Evolution
Chapter 14 Genes, Development, and Evolution
Key Concepts
• 14.1 Development Involves Distinct but
Overlapping Processes
• 14.2 Changes in Gene Expression
Underlie Cell Differentiation in
Development
• 14.3 Spatial Differences in Gene
Expression Lead to Morphogenesis
Chapter 14 Genes, Development, and Evolution
Key Concepts
• 14.4 Gene Expression Pathways Underlie
the Evolution of Development
• 14.5 Developmental Genes Contribute to
Species Evolution but Also Pose
Constraints
Chapter 14 Opening Question
Why are stem cells so useful?
Concept 14.1 Development Involves Distinct but Overlapping
Processes
Development—the process by which a
multicellular organism undergoes a series
of changes, taking on forms that
characterize its life cycle.
After the egg is fertilized, it is called a
zygote.
In its earliest stages, a plant or animal is
called an embryo.
The embryo can be protected in a seed, an
egg shell, or a uterus.
Figure 14.1 Development (Part 1)
Figure 14.1 Development (Part 2)
Concept 14.1 Development Involves Distinct but Overlapping
Processes
Four processes of development:
• Determination sets the fate of the cell
• Differentiation is the process by which
different types of cells arise
• Morphogenesis is the organization and
spatial distribution of differentiated cells
• Growth is an increase in body size by cell
division and cell expansion
Concept 14.1 Development Involves Distinct but Overlapping
Processes
As zygote develops, the cell fate of each
undifferentiated cell drives it to become
part of a particular type of tissue.
Experiments in which specific cells of an
early embryo are grafted to new positions
on another embryo show that cell fate is
determined during development.
Figure 14.2 A Cell’s Fate Is Determined in the Embryo
Concept 14.1 Development Involves Distinct but Overlapping
Processes
Determination is influenced by changes in
gene expression as well as the external
environment.
Determination is a commitment; the final
realization of that commitment is
differentiation.
Differentiation is the actual changes in
biochemistry, structure, and function that
result in cells of different types.
Concept 14.1 Development Involves Distinct but Overlapping
Processes
Determination is followed by
differentiation—under certain conditions a
cell can become undetermined again.
It may become totipotent—able to become
any type of cell.
Plant cells are usually totipotent but can be
induced to dedifferentiate into masses of
calli, which can be cultured into clones.
Genomic equivalence—all cells in a plant
have the complete genome for that plant.
Figure 14.3 Cloning a Plant (Part 1)
Figure 14.3 Cloning a Plant (Part 2)
Concept 14.1 Development Involves Distinct but Overlapping
Processes
In animals, nuclear transfer experiments
have shown that genetic material from a
cell can be used to create cloned animals.
The nucleus is removed from an unfertilized
egg, forming an enucleated egg.
A donor nucleus from a differentiated cell is
then injected into the enucleated egg.
The egg divides and develops into a clone
of the nuclear donor.
Figure 14.4 Cloning a Mammal (Part 1)
Figure 14.4 Cloning a Mammal (Part 2)
Figure 14.4 Cloning a Mammal (Part 3)
Figure 14.4 Cloning a Mammal (Part 4)
Concept 14.1 Development Involves Distinct but Overlapping
Processes
As in plants, no genetic information is lost
as the cell passes through developmental
stages—genomic equivalence.
Practical applications for cloning:
• Expansion of numbers of valuable animals
• Preservation of endangered species
• Preservation of pets
Concept 14.1 Development Involves Distinct but Overlapping
Processes
In plants, growing regions contain
meristems—clusters of undifferentiated,
rapidly dividing stem cells.
Plants have fewer cell types (15–20) than
animals (as many as 200).
In mammals, stem cells occur in most
tissues, especially those that require
frequent replacement—skin, blood,
intestinal lining.
There are about 300 cell types in mammals.
Concept 14.1 Development Involves Distinct but Overlapping
Processes
Stem cells in some mammalian tissues are
multipotent—they produce cells that
differentiate into a few cell types.
Hematopoietic stem cells produce red and
white blood cells.
Mesenchymal stem cells produce bone and
connective tissue cells.
Concept 14.1 Development Involves Distinct but Overlapping
Processes
Multipotent stem cells differentiate “on
demand.”
Stem cells in the bone marrow differentiate
in response to certain signals, which can
be from adjacent cells or from the
circulation.
This is the basis of a cancer therapy called
hematopoietic stem cell transplantation
(HSCP).
Figure 14.5 Multipotent Stem Cells
Concept 14.1 Development Involves Distinct but Overlapping
Processes
Therapies that kill cancer cells can also kill
other rapidly dividing cells such as bone
marrow stem cells.
The stem cells are removed and stored
during the therapy, and then returned to
the bone marrow.
The stored stem cells retain their ability to
differentiate.
Concept 14.1 Development Involves Distinct but Overlapping
Processes
Pluripotent cells in the blastocyst
embryonic stage retain the ability to form
all of the cells in the body.
In mice, embryonic stem cells (ESCs) can
be removed from the blastocyst and grown
in laboratory culture almost indefinitely.
ESCs in the laboratory can also be induced
to differentiate by specific signals, such as
Vitamin A to form neurons or growth
factors to form blood cells.
Figure 14.6 Two Ways to Obtain Pluripotent Stem Cells
Concept 14.1 Development Involves Distinct but Overlapping
Processes
ESC cultures may be sources of
differentiated cells to repair damaged
tissues, as in diabetes or Parkinson’s
disease.
ESCs can be harvested from human
embryos conceived by in vitro fertilization,
with consent of the donors. However:
• Some people object to the destruction of
human embryos for this purpose
• The stem cells could provoke an immune
response in a recipient
Concept 14.1 Development Involves Distinct but Overlapping
Processes
Induced pluripotent stem cells (iPS cells)
can be made from skin cells:
• Microarrays are used to find genes
uniquely expressed at high levels in ESCs.
• The genes are inserted into a vector for
genetic transformation of skin cells—skin
cells express added genes at high levels.
• The transformed cells become iPS cells
and can be induced to differentiate into
many tissues.
Figure 14.6 Two Ways to Obtain Pluripotent Stem Cells
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
Major controls of gene expression in
differentiation are transcriptional controls.
While all cells in an organism have the
same DNA, it can be demonstrated with
nucleic acid hybridization that
differentiated cells have different mRNAs.
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
In the vertebrate embryo, muscle precursor
cells come from a tissue layer called the
mesoderm.
• When these cells commit to becoming
muscle cells, they stop dividing—in many
parts of the embryo, cell division and cell
differentiation are mutually exclusive.
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
• Cell signaling activates the gene for a
transcription factor called MyoD.
• MyoD activates the gene for p21, an
inhibitor of cyclin-dependent kinases that
normally stimulate the cell cycle at G1.
• The cell cycle stops so that differentiation
can begin.
Figure 14.7 Transcription and Differentiation in the Formation of Muscle Cells (Part 1)
Figure 14.7 Transcription and Differentiation in the Formation of Muscle Cells (Part 2)
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
Two ways to make a cell transcribe different
genes:
• Asymmetrical factors that are unequally
distributed in the cytoplasm may end up in
different amounts in progeny cells
• Differential exposure of cells to an inducer
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
Polarity—having a “top” and a “bottom” may
develop in the embryo.
The animal pole is the top, the vegetal pole is
the bottom.
Polarity can lead to determination of cell
fates early in development.
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
Polarity was demonstrated using sea urchin
embryos.
If an eight-cell embryo is cut vertically, it
develops into two normal but small
embryos.
If the eight-cell embryo is cut horizontally, the
bottom develops into a small embryo, the
top does not develop.
In-Text Art, Ch. 14, p. 270
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
Model of cytoplasmic segregation states
that cytoplasmic determinants are
distributed unequally in the egg.
The cytoskeleton contributes to distribution of
cytoplasmic determinants:
• Microtubules and microfilaments have
polarity.
• Cytoskeletal elements can bind certain
proteins.
Figure 14.8 The Concept of Cytoplasmic Segregation (Part 1)
Figure 14.8 The Concept of Cytoplasmic Segregation (Part 2)
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
In sea urchin eggs, a protein binds to the
growing end (+) of a microfilament and to
an mRNA encoding a cytoplasmic
determinant.
As the microfilament grows toward one end
of the cell, it pulls the mRNA along.
The unequal distribution of mRNA results in
unequal distribution of the protein it
encodes.
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
Induction refers to the signaling events in a
developing embryo.
Cells influence one another’s developmental
fate via chemical signals and signal
transduction mechanisms.
Exposure to different amounts of inductive
signals can lead to differences in gene
expression.
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
In C. elegans, the cell divisions from the
fertilized egg to the 959 adult cells can be
followed.
Nematodes are hermaphroditic and contain
male and female reproductive organs.
Eggs are laid through a pore, the vulva.
During development, a single anchor cell
induces the vulva to form from six cells on
the ventral surface of the worm.
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
LIN-3, a protein secreted by the anchor cell
acts as the primary inducer.
The primary precursor cell that received the
most LIN-3 then secretes a secondary
inducer (lateral signal) that acts on its
neighbors.
The gene expression patterns triggered by
these molecular switches determine cell
fates.
Figure 14.9 Induction during Vulval Development in Caenorhabditis elegans (Part 1)
Figure 14.9 Induction during Vulval Development in Caenorhabditis elegans (Part 2)
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
Induction involves the activation or
inactivation of specific genes through
signal transduction cascades in the
responding cells.
Example from nematode development:
Much of development is controlled by the
molecular switches that allow a cell to
proceed down one of two alternative
tracks.
Figure 14.10 The Concept of Embryonic Induction
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Pattern formation—the process that results
in the spatial organization of tissues—
linked with morphogenesis, creation of
body form
Spatial differences in gene expression
depend on:
• Cells in body must “know” where they are
in relation to the body.
• Cells must activate appropriate pattern of
gene expression.
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Programmed cell death—apoptosis—is also
important.
Many cells and structures form and then
disappear during development.
Sequential expression of two genes called
ced-3 and ced-4 (for cell death) are
essential for apoptosis.
Their expression in the human embryo
guides development of fingers and toes.
In-Text Art, Ch. 14, p. 273
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Flowers are composed of four organ types
(sepals, petals, stamens, carpels)
arranged around a central axis in whorls.
In Arabidopsis thaliana, flowers develop from
a meristem at the growing point on the
stem.
The identity of each whorl is determined by
organ identity genes.
Figure 14.11 Gene Expression and Morphogenesis in Arabidopsis Flowers (Part 1)
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Three classes of organ identity genes in
Arabidopsis:
• Class A, expressed in sepals and petals
• Class B, expressed in petals and stamens
• Class C, expressed in stamens and
carpels
Gene regulation is combinatorial—the
composition of active dimers depends on
the location of the cell and determines
which genes will be activated.
Figure 14.11 Gene Expression and Morphogenesis in Arabidopsis Flowers (Part 2)
Figure 14.11 Gene Expression and Morphogenesis in Arabidopsis Flowers (Part 3)
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Two lines of experimental evidence support
the model of organ identity gene function:
• Loss-of-function mutations—mutation in A
results in no sepals or petals; carpels and
stamens form in their place—a homeotic
mutation
• Gain-of-function mutations—promoter for
C can be coupled to A, resulting in only
sepals and petals
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
A gene called LEAFY controls transcription of
organ identity genes.
Plants with loss-of-function mutations of
LEAFY do not produce flowers.
Transgenic orange trees, expressing the
LEAFY gene coupled to a strongly
expressed promoter, flower and fruit years
earlier than normal trees.
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Fate of a cell is often determined by where
the cell is.
Positional information comes in the form
an inducer, a morphogen, which diffuses
from one group of cells to another, setting
up a concentration gradient.
To be a morphogen:
• It must directly affect target cells
• Different concentrations of the morphogen
result in different effects
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
The “French flag model” explains
morphogens and can be applied to
differentiation of the vulva in C. elegans
and to development of vertebrate limbs.
Vertebrate limbs develop from paddleshaped limb buds—cells must receive
positional information.
Cells of the zone of polarizing activity (ZPA)
secrete a morphogen called Sonic
hedgehog (Shh). It forms a gradient that
determines the posterior–anterior axis.
Figure 14.12 The French Flag Model (Part 1)
Figure 14.12 The French Flag Model (Part 2)
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
The fruit fly Drosophila melanogaster has a
body made of different segments.
The head, thorax, and abdomen are each
made of several segments.
24 hours after fertilization a larva appears,
with recognizable segments that look
similar.
The fates of the cells to become different
adult segments are already determined.
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Cytokinesis does not occur in the early
Drosophila mitoses after fertilization.
The embryo until then is multinucleate,
allowing for easy diffusion of morphogens.
Experimental genetics were used:
• Developmental mutant strains were
identified.
• Genes for mutations were identified.
• Transgenic flies were produced to confirm
the developmental pathway.
In-Text Art, Ch. 14, p. 276 (1)
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Several types of genes are expressed
sequentially to define the segments:
• Maternal effect genes set up anterior–
posterior and dorsal–ventral axes in the
egg.
• Segmentation genes determine
boundaries and polarity.
• Hox genes determine what organ will be
made at a given location.
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Maternal effect genes produce cytoplasmic
determinants in unequal distributions in
the egg.
Two genes—bicoid and nanos—determine
the anterior–posterior axis.
Their mRNAs diffuse to the anterior end of
the egg.
Bicoid protein diffuses away from the anterior
end, establishing a gradient.
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
At sufficient concentration, bicoid stimulates
transcription of the Hunchback gene. A
gradient of that protein establishes the
head.
Nanos mRNA is transported to the posterior
end. Nanos protein inhibits translation of
Hunchback.
After the anterior and posterior ends are
established, the next step is determination
of segment number and locations.
In-Text Art, Ch. 14, p. 276 (2)
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Segmentation genes determine properties
of the larval segments.
Three classes of genes act in sequence:
• Gap genes organize broad areas along
the axis
• Pair rule genes divide embryo into units
of two segments each
• Segment polarity genes determine
boundaries and anterior–posterior
organization in individual segments
Figure 14.13 A Gene Cascade Controls Pattern Formation in the Drosophila Embryo
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Hox genes are expressed in different
combinations along the length of the
embryo.
They determine cell fates within each
segment and direct cells to become
certain structures, such as eyes or wings.
Hox genes are homeotic genes that are
shared by all animals.
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Clues to hox gene function came from
homeotic mutants.
Antennapedia mutation—legs grow in place
of antennae.
Bithorax mutation—an extra pair of wings
grow.
Figure 14.14 A Homeotic Mutation in Drosophila (Part 1)
Figure 14.14 A Homeotic Mutation in Drosophila (Part 2)
Concept 14.3 Spatial Differences in Gene Expression Lead to
Morphogenesis
Antennapedia and bithorax have a common
180-bp sequence—the homeobox, that
encodes a 60-amino acid sequence called
the homeodomain.
The homeodomain binds to a specific DNA
sequence in promoters of target genes.
Concept 14.4 Gene Expression Pathways Underlie the Evolution
of Development
Discovery of developmental genes allowed
study of other organisms.
The homeobox is also present in many
genes in other organisms, showing a
similarity in the molecular events of
morphogenesis.
Evolutionary developmental biology (evodevo) is the study of evolution and
developmental processes.
Concept 14.4 Gene Expression Pathways Underlie the Evolution
of Development
Principles of evo-devo:
• Many groups of animals and plants share
similar molecular mechanisms for
morphogenesis and pattern formation.
• The molecular pathways that determine
different developmental processes
operate independently from one another—
called modularity.
Concept 14.4 Gene Expression Pathways Underlie the Evolution
of Development
• Changes in location and timing of
expression of particular genes are
important in the evolution of new body
forms and structures.
• Development produces morphology, and
morphological evolution occurs by
modification of existing developmental
pathways—not through new mechanisms.
Concept 14.4 Gene Expression Pathways Underlie the Evolution
of Development
Through hybridization, sequencing, and
comparative genomics, it is known that
diverse animals share molecular
pathways for gene expression in
development.
Fruit fly genes have mouse and human
orthologs for developmental genes.
These genes are arranged on the
chromosome in the same order as they
are expressed along the anterior–
posterior axis of their embryos—the
positional information has been
conserved.
Figure 14.15 Regulatory Genes Show Similar Expression Patterns
Concept 14.4 Gene Expression Pathways Underlie the Evolution
of Development
Certain developmental mechanisms,
controlled by specific DNA sequences,
have been conserved over long periods
during the evolution of multicellular
organisms.
These sequences comprise the genetic
toolkit, which has been modified over the
course of evolution to produce the
diversity of organisms in the world today.
Concept 14.4 Gene Expression Pathways Underlie the Evolution
of Development
In an embryo, genetic switches integrate
positional information and play a key role
in making different modules develop
differently.
Genetic switches control the activity of Hox
genes by activating each Hox gene in
different zones of the body.
The same switch can have different effects
on target genes in different species,
important in evolution.
Figure 14.16 Segments Differentiate under Control of Genetic Switches (Part 1)
Figure 14.16 Segments Differentiate under Control of Genetic Switches (Part 2)
Concept 14.4 Gene Expression Pathways Underlie the Evolution
of Development
Modularity also allows the timing of
developmental processes to be
independent—heterochrony.
Example: The giraffe’s neck has the same
number of vertebrae as other mammals,
but the bones grow for a longer period.
The signaling process for stopping growth is
delayed—changes in the timing of gene
expression led to longer necks.
Figure 14.17 Heterochrony in the Development of a Longer Neck
Concept 14.4 Gene Expression Pathways Underlie the Evolution
of Development
Webbed feet in ducks result from an altered
spatial expression pattern of a
developmental gene.
Duck and chicken embryos both have
webbing, and both express BMP4, a
protein that instructs cells in the webbing
to undergo apoptosis.
Concept 14.4 Gene Expression Pathways Underlie the Evolution
of Development
In ducks, a gene called Gremlin, which
encodes a BMP inhibitor protein, is
expressed in webbing cells.
In chickens, Gremlin is not expressed, and
BMP4 signals apoptosis of the webbing
cells.
Experimental application of Gremlin to
chicken feet results in a webbed foot.
Figure 14.18 Changes in Gremlin Expression Correlate with Changes in Hindlimb Structure
Concept 14.5 Developmental Genes Contribute to Species
Evolution but Also Pose Constraints
Evolution of form has not been a result of
radically new genes but has resulted from
modifications of existing genes.
Developmental genes constrain evolution in
two ways:
• Nearly all evolutionary innovations are
modifications of existing structures.
• Genes that control development are highly
conserved.
Concept 14.5 Developmental Genes Contribute to Species
Evolution but Also Pose Constraints
Genetic switches that determine where and
when genes are expressed underlie both
development and the evolution of
differences among species.
Among arthropods, the Hox gene Ubx
produces different effects.
In centipedes, Ubx protein activates the Dll
gene to promote the formation of legs.
In insects, a change in the Ubx gene results
in a protein that represses Dll expression,
so leg formation is inhibited.
Figure 14.19 A Mutation in a Hox Gene Changed the Number of Legs in Insects
Concept 14.5 Developmental Genes Contribute to Species
Evolution but Also Pose Constraints
Wings arose as modifications of existing
structures.
In vertebrates, wings are modified limbs.
Organisms also lose structures.
Ancestors of snakes lost their forelimbs as a
result of changes in expression of Hox
genes.
Then hindlimbs were lost by the loss of
expression of the Sonic hedgehog gene in
limb bud tissue.
Figure 14.20 Wings Evolved Three Times in Vertebrates
Concept 14.5 Developmental Genes Contribute to Species
Evolution but Also Pose Constraints
Many developmental genes exist in similar
form across a wide range of species.
Highly conserved developmental genes
make it likely that similar traits will evolve
repeatedly: Parallel phenotypic
evolution.
Example: Three-spined sticklebacks
(Gasterosteus aculeatus)
Concept 14.5 Developmental Genes Contribute to Species
Evolution but Also Pose Constraints
Marine populations of sticklebacks return to
freshwater to breed. Freshwater
populations never go into saltwater
environments.
Freshwater populations have arisen many
times from adjacent marine populations.
Marine populations have pelvic spines and
bony plates that protect them from
predation.
These are greatly reduced in freshwater
populations.
Figure 14.21 Parallel Phenotypic Evolution in Sticklebacks
Concept 14.5 Developmental Genes Contribute to Species
Evolution but Also Pose Constraints
One gene, Pitx1, is not expressed in
freshwater sticklebacks, and spines do not
develop.
This same gene has evolved to produce
similar phenotypic changes in several
independent populations.
Answer to Opening Question
Stem cells are valuable because they are
not differentiated and can develop into
several kinds of cells.
When fat stem cells are injected into a
damaged area they respond to the
environment of that tissue.
Inducers in the environment determine
the products of cell differentiation.
Figure 14.22 Differentiation Potential of Stem Cells from Fat