Genes, Development, and Evolution 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 Fate Determination and Differentiation 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis

Chapter 14 Genes, Development, and Evolution Key Concepts 14.4 Changes in Gene Expression Pathways Underlie the Evolution of Development 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints

Chapter 14 Opening Question How do gene products control the development of the eye?

Concept 14.1 Development Involves Distinct but Overlapping Processes Development—changes a multicellular organism undergoes as it progresses from a single cell to an embryo and to mature adulthood Zygote—fertilized egg Embryo—earliest developmental stages Many organisms continue to develop throughout their lives, with development ceasing only at death.

Figure 14.1 Development Figure 14.1 Development Selected stages and processes of development from zygote to maturity are shown for an animal and for a plant. The blastula is a hollow sphere of cells; the gastrula has three cell layers (indicated by blue, red, and yellow).

Concept 14.1 Development Involves Distinct but Overlapping Processes Processes that underlie development: Determination—sets fate of a cell Differentiation—different types of cells arise from less specialized cells Morphogenesis—organization and spatial distribution of differentiated cells Growth—increase in body size by cell division and expansion All involve differential gene expression and signaling between cells.

Concept 14.1 Development Involves Distinct but Overlapping Processes As a zygote develops, each undifferentiated cell is destined to become part of a particular tissue—the cell fate. Experiments in which specific cells of an early embryo are transplanted to new positions on another embryo show when cell fate is determined. Determination is influenced by changes in gene expression and by the external environment.

Figure 14.2 A Cell’s Fate Is Determined in the Embryo Figure 14.2 A Cell’s Fate Is Determined in the Embryo Transplantation experiments using frog embryos show that the fate of cells is determined as the early embryo develops.

Concept 14.1 Development Involves Distinct but Overlapping Processes During animal development, cell fate becomes progressively restricted. Cell potency—a cell’s potential to differentiate: Early embryo cells are totipotent—they can become any type of cell. In later stages, some cells may be pluripotent—can develop into most other cell types, but cannot form new embryos.

Concept 14.1 Development Involves Distinct but Overlapping Processes Some cells remain multipotent through adult stages—can differentiate into several related cell types. Many cells in a mature organism are unipotent—produce only the same cell type.

Concept 14.1 Development Involves Distinct but Overlapping Processes Under certain conditions, a determined or differentiated cell can become undetermined again, even totipotent. Some plant cells can be grown in culture and induced to dedifferentiate. If given the right chemical cues, these cells can develop into new plants (clones of the original plants).

Figure 14.3 Cloning a Plant (Part 1) Figure 14.3 Cloning a Plant When cells were removed from a plant and put into a medium with nutrients and hormones, they lost many of their specialized features—they dedifferentiated and became totipotent.a [a F. C. Steward et al. 1958. American Journal of Botany 45: 705–709.]

Figure 14.3 Cloning a Plant (Part 2) Figure 14.3 Cloning a Plant When cells were removed from a plant and put into a medium with nutrients and hormones, they lost many of their specialized features—they dedifferentiated and became totipotent.a [a F. C. Steward et al. 1958. American Journal of Botany 45: 705–709.]

Concept 14.1 Development Involves Distinct but Overlapping Processes This cloning technique is used extensively in agriculture and forestry. The ability to produce clones is evidence for the genomic equivalence of somatic cells: All somatic cells in a plant have a complete genome and thus all the genetic information needed to become any cell in the plant.

Concept 14.1 Development Involves Distinct but Overlapping Processes In animals, nuclear transfer experiments show 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 The experimental procedure described here was used to produce the first cloned mammal, a Dorset sheep named Dolly (shown on the left in the photo). As an adult, Dolly mated and subsequently gave birth to a normal offspring (the lamb on the right), thus proving the genetic viability of cloned mammals.a [a I. Wilmut et al. 1997. Nature 385: 810–813.]

Figure 14.4 Cloning a Mammal (Part 2) Figure 14.4 Cloning a Mammal The experimental procedure described here was used to produce the first cloned mammal, a Dorset sheep named Dolly (shown on the left in the photo). As an adult, Dolly mated and subsequently gave birth to a normal offspring (the lamb on the right), thus proving the genetic viability of cloned mammals.a [a I. Wilmut et al. 1997. Nature 385: 810–813.]

Figure 14.4 Cloning a Mammal (Part 3) Figure 14.4 Cloning a Mammal The experimental procedure described here was used to produce the first cloned mammal, a Dorset sheep named Dolly (shown on the left in the photo). As an adult, Dolly mated and subsequently gave birth to a normal offspring (the lamb on the right), thus proving the genetic viability of cloned mammals.a [a I. Wilmut et al. 1997. Nature 385: 810–813.]

Concept 14.1 Development Involves Distinct but Overlapping Processes Many animals have now been cloned; their differentiated cells also have genomic equivalence. Practical applications: Increase the numbers of transgenic animals with valuable phenotypes (e.g., cows that produce human growth hormone) Preservation of endangered species with low reproduction rates

Concept 14.1 Development Involves Distinct but Overlapping Processes Resurrection of extinct species from intact fossil DNA The genomes of some extinct species have been sequenced, including wooly mammoths and Neanderthals.

Concept 14.1 Development Involves Distinct but Overlapping Processes In adult plants, growing regions at the tips of roots and stems contain meristems—clusters of undifferentiated, rapidly dividing stem cells. The plant body undergoes constant growth and renewal, with new organs forming often.

Concept 14.1 Development Involves Distinct but Overlapping Processes In adult mammals, stem cells occur in many 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. In bone marrow: Hematopoietic stem cells produce red and white blood cells. Mesenchymal stem cells produce bone and surrounding tissue, including muscle.

Concept 14.1 Development Involves Distinct but Overlapping Processes Multipotent stem cells differentiate “on demand.” Hematopoietic cells differentiate in response to signals from adjacent cells or from the circulating blood. This is the basis of a cancer therapy called hematopoietic stem cell transplantation (HSCT).

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, or they may come from a donor. After treatment, the stem cells, which retain their ability to differentiate, are injected back into the patient.

Figure 14.5 Multipotent Stem Cells Figure 14.5 Multipotent Stem Cells In hematopoietic stem cell transplantation, blood stem cells are used to replace stem cells destroyed by cancer therapy.

Concept 14.1 Development Involves Distinct but Overlapping Processes In mammals, some pluripotent cells in the blastocyst embryonic stage retain the ability to form all of the cells in the body—called embryonic stem cells (ESCs). They can be removed from a blastocyst and grown in laboratory culture almost indefinitely; they can differentiate when proper signals are provided.

Concept 14.1 Development Involves Distinct but Overlapping Processes ESCs might be useful in repairing damage caused by diseases such as diabetes and Parkinson’s disease. ESCs can be harvested from human embryos conceived by in vitro fertilization. Problems with this approach include: Objections to the destruction of human embryos for this purpose The stem cells could provoke an immune response in a recipient

Figure 14.6 Two Ways to Obtain Pluripotent Stem Cells Figure 14.6 Two Ways to Obtain Pluripotent Stem Cells Pluripotent stem cells can be obtained either from (A) human embryos or (B) by adding genes that are highly expressed in stem cells to skin cells to transform them into stem cells.

Concept 14.1 Development Involves Distinct but Overlapping Processes An alternative was developed by Yamanaka and coworkers: Induced pluripotent stem cells (iPS cells) can be made from skin cells. Microarrays were used to find genes uniquely expressed in ESCs. They encode transcription factors essential to stem cell function.

Concept 14.1 Development Involves Distinct but Overlapping Processes The genes were inserted into a vector for genetic transformation of skin cells. The transformed cells were pluripotent and could be induced to differentiate into many tissue types.

Cell fate can be determined by: Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation Genes that determine cell fate and trigger differentiation usually encode transcription factors. Cell fate can be determined by: Asymmetrical distribution of cytoplasmic factors in a cell, so the progeny cells receive unequal amounts of the factors Differential exposure of two cells to an external signal (an inducer)

Polarity—having a “top” (animal pole) and a “bottom” (vegetal pole) Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation Axes that relate to the body plan of the organism are established early in development. Polarity—having a “top” (animal pole) and a “bottom” (vegetal pole) Polarity can lead to determination of cell fates early in development.

Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation Sea urchin embryos can be bisected at the eight-cell stage in two different ways:

If the two halves are allowed to develop: Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation If the two halves are allowed to develop: In an embryo cut into top and bottom halves, the bottom develops into a small sea urchin and the top half does not develop at all. In an embryo cut into two side halves, both halves develop normally, though smaller. Indicates that the top and bottom halves have already developed distinct fates.

Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation The model of cytoplasmic segregation states that cytoplasmic determinants are distributed unequally in the egg. Cytoplasmic determinants include transcription factors that promote differential gene expression in the two daughter cells. Small regulatory RNAs and mRNAs also contribute to differential gene expression.

Figure 14.7 The Concept of Cytoplasmic Segregation Figure 14.7 The Concept of Cytoplasmic Segregation (A) The unequal distribution of cytoplasmic determinants in a fertilized egg determines the fates of its descendants. (B) The zygote of the nematode worm Caenorhabditis elegans (left) shows an asymmetrical distribution of cytoplasmic particles (stained green). The progeny of the first cell division (right) receive unequal amounts of the particles.

Microtubules and microfilaments have polarity. Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation The cytoskeleton contributes to the distribution of cytoplasmic determinants: Microtubules and microfilaments have polarity. Cytoskeletal elements can bind certain proteins that can be used in the transport of mRNA.

Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation Induction: signaling events by which cells in a developing embryo communicate and influence one another’s developmental fate Cells influence one another’s developmental fate via chemical signals (inducers) and signal transduction mechanisms.

Development of C. elegans is easily observed under a microscope. Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation Development of C. elegans is easily observed under a microscope. All of the cell divisions from zygote to the 959 cells in the adult can be followed. Nematodes are hermaphroditic, containing both male and female reproductive organs. Eggs are laid through a pore, the vulva.

Figure 14.8 Induction during Vulval Development in Caenorhabditis elegans (Part 1) Figure 14.8 Induction during Vulval Development in Caenorhabditis elegans (A) In the nematode C. elegans (shown in false color here), it has been possible to follow all of the cell divisions from the fertilized egg to the 959 cells found in the fully developed adult. (B) During vulval development, a molecule secreted by the anchor cell (the LIN-3 protein) acts as the primary (1°) inducer. The primary precursor cell (the one that received the highest concentration of LIN-3) then secretes a secondary (2°) inducer that acts on its neighbors. The gene expression patterns triggered by these molecular switches determine cell fates.

Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation During development, an anchor cell induces the vulva to form from 6 cells on the ventral surface. Anchor cell secretes LIN-3 (primary inducer). Concentration of LIN-3 is key—it diffuses out of the anchor cell and forms a concentration gradient. The primary precursor cell gets the most LIN- 3, and it secretes a secondary inducer.

Figure 14.8 Induction during Vulval Development in Caenorhabditis elegans (Part 2) Figure 14.8 Induction during Vulval Development in Caenorhabditis elegans (A) In the nematode C. elegans (shown in false color here), it has been possible to follow all of the cell divisions from the fertilized egg to the 959 cells found in the fully developed adult. (B) During vulval development, a molecule secreted by the anchor cell (the LIN-3 protein) acts as the primary (1°) inducer. The primary precursor cell (the one that received the highest concentration of LIN-3) then secretes a secondary (2°) inducer that acts on its neighbors. The gene expression patterns triggered by these molecular switches determine cell fates.

Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation Induction involves the activation or inactivation of specific genes through signal transduction cascades in the responding cells. Much of development is controlled by the molecular switches that allow a cell to proceed down one of two alternative paths.

Figure 14.9 The Concept of Embryonic Induction Figure 14.9 The Concept of Embryonic Induction The concentration of an inducer directly affects the degree to which a transcription factor is activated. The inducer acts by binding to a receptor on the target cell. This binding is followed by signal transduction involving transcription factor activation or movement from the cytoplasm to the nucleus. In the nucleus, the transcription factor acts to stimulate the expression of genes involved in cell differentiation.

A key event in commitment is that the cells stop dividing. Concept 14.2 Changes in Gene Expression Underlie Cell Fate Determination and Differentiation An important mechanism for cell differentiation is differential gene transcription. A well-studied example is the conversion of undifferentiated muscle precursor cells (myoblasts) into muscle fiber cells. A key event in commitment is that the cells 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 Fate Determination and Differentiation 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, and other transcription factors trigger differentiation.

Figure 14.10 Transcription and Differentiation in the Formation of Muscle Cells Figure 14.10 Transcription and Differentiation in the Formation of Muscle Cells Activation of the transcription factor MyoD is important in muscle cell differentiation.

Cells must activate the appropriate pattern of gene expression. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Pattern formation: processes that result in the spatial organization of a tissue or organism; results from spatial differences in gene expression Cells in body must “know” where they are in relation to the rest of the body. Cells must activate the appropriate pattern of gene expression.

Fate of a cell often depends on its location. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Fate of a cell often depends on its location. Positional information, or “spatial sense,” often comes in the form of an inducer, or morphogen. Morphogens diffuse from one group of cells to another, setting up a concentration gradient. Different concentrations of the morphogen result in different effects.

The “French flag model” explains morphogen action. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis The “French flag model” explains morphogen action. Vertebrate limbs develop from limb buds; the cells must receive positional information to develop properly. Cells in the zone of polarizing activity (ZPA) secrete a morphogen called Sonic hedgehog (Shh). A gradient of Shh determines the posterior– anterior axis.

Figure 14.11 The French Flag Model Figure 14.11 The French Flag Model (A) In the “French flag model,” a concentration gradient of a diffusible morphogen signals each cell to specify its position. (B) The zone of polarizing activity (ZPA) in the limb bud of the embryo secretes the morphogen Sonic hedgehog (Shh). Cells in the bud form different digits depending on the concentration of Shh.

Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Development also involves programmed cell death (apoptosis). It is required, for instance, to remove connective tissue cells between the fingers and toes.

Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Model organisms are used to study apoptosis in development. C. elegans produces 1090 cells but 131 die, leaving 959 cells in the adult. Sequential activation of two proteins (CED-4 and CED-3) is essential for apoptosis. CED-9 on mitochondria inhibits apoptosis in cells that are not programmed to die. It binds CED-4 and prevents it from activating CED-3.

Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis If the cell gets a signal for apoptosis, CED-9 releases CED-4, which activates CED-3.

Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Proteins involved in the nematode apoptosis pathway have counterparts in humans. The commonality of this pathway indicates its importance: most mutations in genes that control this pathway are harmful and evolution selects against them.

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 tip (undifferentiated, rapidly dividing cells). The identity of each whorl is determined by three classes of organ identity genes.

Figure 14.12 ABC Model for Gene Expression and Morphogenesis in Arabidopsis thaliana Flowers Figure 14.12 ABC Model for Gene Expression and Morphogenesis in Arabidopsis thaliana Flowers (A) The four organs of a flower—sepals (pink), petals (purple), stamens (green), and carpels (yellow)—grow in whorls that develop from the floral meristem. (B) Floral organs are determined by three classes of genes whose polypeptide products combine in pairs to form transcription factors. (C) Combinations of polypeptide subunits in transcription factors activate gene expression for specific organs.

Class A—expressed in sepals and petals Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Class A—expressed in sepals and petals Class B—expressed in petals and stamens Class C—expressed in stamens and carpels The genes encode transcription factors that act as dimers—proteins with two subunits. Composition of the dimer determines which genes are activated.

Two lines of evidence support this model: Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Two lines of evidence support this model: Loss-of-function mutations—such as, a mutation in A results in no sepals or petals Gain-of-function mutations—promoter for C can be coupled to A, resulting in only sepals and petals Replacement of one organ by another is called homeosis; this type of mutation is a homeotic mutation.

LEAFY also controls transcription of floral organ identity genes. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis LEAFY also controls transcription of floral organ identity genes. Plants with loss-of-function mutations in the LEAFY gene 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.

Development is also studied in Drosophila melanogaster. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Development is also studied in Drosophila melanogaster. Insect bodies are segmented, with three regions—head, thorax, abdomen. Each segment gives rise to different body parts—antennae and eyes develop from head segments, wings from the thorax. Fates of the cells to become different segments are determined by 24 hours after fertilization.

Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Cytokinesis does not occur with the first 12 divisions, resulting in a multinucleate embryo.

To study fate determination in the 1st 24 hours: Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis To study fate determination in the 1st 24 hours: Developmental mutations were identified. Mutants were compared with wild-type flies to identify the genes responsible. Experiments with transgenic flies and proteins confirmed proposed developmental pathways.

Maternal effect genes set up the major axes in the egg. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis These approaches revealed a sequential pattern of gene expression that results in fate determination: Maternal effect genes set up the major axes in the egg. Segmentation genes determine boundaries and polarity of segments. Hox genes determine what organ will be made at a given location.

Bicoid and nanos determine the anterior– posterior axis. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Maternal effect genes produce cytoplasmic determinants. They are transcribed in the ovary cells, and the mRNAs are passed to the egg via cytoplasmic bridges. Bicoid and nanos determine the anterior– posterior axis. Their mRNAs diffuse to the anterior end of the egg and bicoid protein diffuses away, establishing a gradient.

Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Bicoid stimulates transcription of hunchback, resulting in a gradient of Hunchback protein which establishes the head region.

Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Nanos mRNA is transported to the posterior end. Nanos protein inhibits translation of hunchback. The next step is determination of number, boundaries, and polarity of the larval segments by proteins encoded by the segmentation genes.

Three classes of segmentation genes act in sequence: Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Three classes of segmentation genes act in sequence: Gap genes organize broad areas along the anterior–posterior axis. Pair rule genes divide the 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 Figure 14.13 A Gene Cascade Controls Pattern Formation in the Drosophila Embryo Maternal effect genes induce gap, pair rule, and segment polarity genes—collectively referred to as segmentation genes. By the end of this cascade, a group of nuclei at the anterior of the embryo, for example, is determined to become the first head segment in the adult fly. In the micrographs at left, various staining methods have been used to highlight the different gene products.

Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Hox genes encode transcription factors that 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 and are functionally similar to organ identity genes in plants.

Clues to hox gene function came from homeotic mutants. Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Clues to hox gene function came from homeotic mutants. A gain-of-function mutation in the Antennapedia gene causes legs to grow on the head in place of antennae A mutation in bithorax causes an extra pair of wings to grow.

Figure 14.14 A Homeotic Mutation in Drosophila Figure 14.14 A Homeotic Mutation in Drosophila Mutations of the Hox genes cause body parts to form on inappropriate segments. (A) A wild-type fruit fly. (B) An Antennapedia mutant fruit fly. Mutations such as this reveal the normal role of the Antennapedia gene in determining segment function.

Concept 14.3 Spatial Differences in Gene Expression Lead to Morphogenesis Hox genes have a common 180-bp sequence—the homeobox, that encodes a 60-amino acid sequence called the homeodomain. The homeodomain binds to specific DNA sequences in promoters of target genes.

Concept 14.4 Changes in Gene Expression Pathways Underlie the Evolution of Development When scientists used homeobox DNA as a hybridization probe to search for similar genes, they found the homeobox in many genes in many other organisms. Biologists began to ask new questions about the interplay between evolutionary and developmental processes, and evolutionary developmental biology (evo-devo) was born.

Major findings of evo-devo: Concept 14.4 Changes in Gene Expression Pathways Underlie the Evolution of Development Major findings of evo-devo: Organisms share similar molecular mechanisms for development, including a “toolkit” of regulatory molecules that control gene expression. The regulatory molecules act independently in different tissues and regions of the body, so evolutionary change can occur in independent “modules.”

Concept 14.4 Changes in Gene Expression Pathways Underlie the Evolution of Development Developmental differences can arise from changes in the timing of action of a regulatory molecule, the location of its action, or the quantity of its action. Developmental changes can arise from environmental influences on developmental processes.

Concept 14.4 Changes in Gene Expression Pathways Underlie the Evolution of Development DNA hybridization, genome sequencing, and comparative genomics have shown that diverse animals share molecular pathways for gene expression in development. Fruit fly homeotic genes are similar to mammal genes that play similar developmental roles. Conservation of these genes over millions of years suggests that their functions are essential for animal development.

Concept 14.4 Changes in Gene Expression Pathways Underlie the Evolution of Development These genes are arranged on a chromosome in both fruit fly and mouse in the same order as they are expressed along the anterior– posterior axis of the embryo.

Figure 14.15 Regulatory Genes Show Similar Expression Patterns Figure 14.15 Regulatory Genes Show Similar Expression Patterns Similar genes encoding similar transcription factors are expressed in similar patterns along the anterior–posterior axis of both insects and vertebrates. Orthologous genes and the locations of their expression are indicated by shared colors. The mouse (and human) Hox genes are actually present in multiple copies; this prevents a single mutation from having drastic effects.

Concept 14.4 Changes in Gene Expression Pathways Underlie the Evolution of Development Certain developmental mechanisms, controlled by specific DNA sequences, have been conserved 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 Changes in Gene Expression Pathways Underlie the Evolution of Development Genetic switches control how the genetic toolkit is used in an individual organism. Multiple switches (promoters and transcription factors) control each gene by influencing its expression at different times and in different places. During evolution, changes in function of genetic switches have led to changes in the forms or functions of organisms.

Figure 14.16 Segments Differentiate under Control of Genetic Switches Figure 14.16 Segments Differentiate under Control of Genetic Switches The binding of a single protein, Ultrabithorax (Ubx), determines whether a thoracic segment in Drosophila produces full wings or halteres (balancers).

Concept 14.4 Changes in Gene Expression Pathways Underlie the Evolution of Development Modularity of development means that the molecular pathways for developmental processes operate independently. On an evolutionary time scale, the timing and position of a developmental process can change without disrupting the whole organism.

Concept 14.4 Changes in Gene Expression Pathways Underlie the Evolution of Development Heterochrony: changes in timing or duration of gene expression 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 Figure 14.17 Heterochrony in the Development of a Longer Neck There are seven vertebrae in the neck of the giraffe (left) and human (right; not to scale). But the vertebrae of the giraffe are much longer (25 cm compared with 1.5 cm) because during development, growth continues for a longer period of time. This timing difference is called heterochrony.

Example: difference in foot webbing in ducks versus chickens Concept 14.4 Changes in Gene Expression Pathways Underlie the Evolution of Development Heterotopy: changes in the spatial pattern of expression of a developmental gene Example: difference in foot webbing in ducks versus chickens Duck and chicken embryos both have webbing and express BMP4, a protein that instructs webbing cells to undergo apoptosis. But duck embryos express Gremlin, which encodes a BMP inhibitor protein.

Figure 14.18 Changes in Gremlin Expression Correlate with Changes in Hindlimb Structure Figure 14.18 Changes in Gremlin Expression Correlate with Changes in Hindlimb Structure The left column of photos shows the development of a chicken’s foot; the right column shows foot development in a duck. Gremlin protein in the webbing of the duck foot inhibits BMP4 signaling, thus preventing the embryonic webbing from undergoing apoptosis.

Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints The genetic toolkit also places constraints on how radically organisms can differ from one another. Evolution of form has not been a result of radically new genes but has resulted from modifications of existing genes and their regulatory pathways.

Developmental genes constrain evolution in two ways: Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints 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 Heterotypy: a major developmental change due to change in a regulatory molecule (rather than where, when, or how much it is expressed) Example: All arthropods express a gene called Distalless (Dll) that controls segmental leg development. In insects, Dll expression is repressed in abdominal segments by the Hox gene Ubx.

Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints In centipedes, Ubx protein activates expression of Dll to promote formation of legs. During the evolution of insects, a change in the Ubx gene resulted in a modified Ubx protein that represses Dll expression in abdominal segments.

Figure 14.19 A Mutation in a Hox Gene Changed the Number of Legs in Insects Figure 14.19 A Mutation in a Hox Gene Changed the Number of Legs in Insects In the insect lineage (blue box) of the arthropods, a change to the Ubx gene resulted in a protein that inhibits the Dll gene, which is required for legs to form. Because insects express this modified Ubx gene in their abdominal segments, no legs grow from these segments. Other arthropods, such as centipedes, do grow legs from their abdominal segments.

Example: Wings arose as modifications of existing structures. Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints Features of organisms almost always evolve from preexisting features in their ancestors. Example: Wings arose as modifications of existing structures. In vertebrates, the wings are modified limbs.

Figure 14.20 Wings Evolved Three Times in Vertebrates Figure 14.20 Wings Evolved Three Times in Vertebrates The wings of pterosaurs (the earliest flying vertebrates, which lived from 265 to 220 million years ago), birds, and bats are all modified forelimbs constructed from the same skeletal components. However, the components have different forms in the different groups of vertebrates.

Organisms also lose structures: Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints Organisms also lose structures: Ancestors of snakes lost their forelimbs as a result of changes in segmental expression of Hox genes. Then hindlimbs were lost by the loss of expression of the Sonic hedgehog gene in limb bud tissue. Some snake species still have rudimentary pelvic bones and upper leg bones.

Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints Parallel phenotypic evolution: highly conserved developmental genes make it likely that similar traits will evolve repeatedly Example: Marine and freshwater populations of three-spined sticklebacks (Gasterosteus aculeatus) Genetic evidence shows that freshwater populations have arisen independently from marine populations many times in different parts of the world.

These are greatly reduced in freshwater populations. Concept 14.5 Developmental Genes Contribute to Species Evolution but Also Pose Constraints Marine populations have pelvic spines and bony plates that protect them from predation. These are greatly reduced in freshwater populations. The Pitx1 gene codes for a transcription factor that is normally expressed in marine populations but not in freshwater populations.

Figure 14.21 Parallel Phenotypic Evolution in Sticklebacks Figure 14.21 Parallel Phenotypic Evolution in Sticklebacks A developmental gene, Pitx1, encodes a transcription factor that stimulates the production of plates and spines. This gene is active in marine sticklebacks (indicated by arrowheads in inset at left) but is mutated and inactive in various freshwater populations of the fish. The fact that this mutation is found in geographically distant and isolated freshwater populations is evidence for parallel evolution.

Answer to Opening Question The product of both the fruit fly eyeless gene and the vertebrate Pax6 gene is a transcription factor produced in the front of the developing brain. The resulting “eye field” separates into two eyes when cells in the middle of the region produce Shh (sonic hedgehog). Shh is a transcription factor that blocks the synthesis of Pax6, so no eye forms there.

Answer to Opening Question In cave-dwelling fish, Shh occurs over a wider area of the eye field, and adults have no eyes. If too little or no Shh is made, a single eye is formed; this occurs in the human disorder known as cyclopia.

Figure 14.22 Inhibition of a Molecular Switch Results in No Eyes Figure 14.22 Inhibition of a Molecular Switch Results in No Eyes (A) In the Mexican tetra fish (Astyanax mexicanus), fish dwelling on the surface have two eyes (left), whereas those living in dark caves have no eyes (right). The difference results from overexpression of the Shh gene in cave-dwelling fish (B), which inhibits production of the molecular switch made by the Pax6 gene (C).