Opportunities in Biology (1989) / Chapter Skim
Currently Skimming:
4. Genes and Cells
4. Genes and Cells
Pages 77-139
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 77... ...
These interactions regulate the capacity of cells to multiply, to differentiate into the hundreds of different cell types that make up our bodies, and to organize themselves into tissues, organs, and finally the human body itself, according to a specific, well-defined architectural plan. This cycle of activity characterizes normal healthy individuals, but the process can go awry, leading to abno~n~al states characterized by disease in humans, animals, and plants.
|
From page 78... ...
, protein synthesis, and gene transcription. This strategy has yielded a biochemical inventory and, in addition, a rather detailed functional characterization of each organelle showing that func
|
From page 79... ...
Similarly, protein synthesis can be reconstituted in vitro from different components from plant and animal cells. Fruit flies, sea urchins, and chickens have all been excellent sources of model systems for analyzing cell behavior during embryonic development.
|
From page 80... ...
Separation of chromosomes from the cytoplasmic space is thought to ensure proper regulation of nucleic acid and protein synthesis in the cell. Except at the time of mitosis, when the nuclear envelope breaks down, all molecular traffic between the nucleus and cytoplasm is by way of this envelope, which consists of two parallel membranes joined at regions called nuclear pores.
|
From page 81... ...
Selective RNAs are pumped out of the nucleus through the same pores. For the transported proteins, the specificity is known to reside in a short sequence of their amino acids that seems to be recognized by a component of the nuclear pore.
|
From page 82... ...
Fortunately, however, the genome does not remain in the dispersed state characteristic of physiological activity during the entire cell cycle. At cell division (mitosis)
|
From page 83... ...
Telomere sequences are added to the ends of chromosomes at the time of chromosome replication by a special enzyme or enzymes without the need for a DNA template, and in this way they form a protective cap at each end of a chromosome. Artificial Chromosomes Are Valuable Research Tools The identification of centromeres and telomeres as well as sequences that initiate DNA replication now permits the synthesis of artificial "minichromosomes" by genetic engineering techniques.
|
From page 84... ...
In particular, we are just beginning to learn about the nbosomal proteins and the ways they interact with rRNA to form the ribosomes. Ribosomes themselves are crucially unportant to cell function, since they are the machines Hat catalyze all protein synthesis.
|
From page 85... ...
Mutations can be found that lead to the requirement that an amino acid, say histidine, which the cells would normally produce itself, be supplied in the growth medium. Mutations of this type are extremely useful because the cells can be maintained and genetic crosses can be made on complete medium, yet the mutation can be detected at any time by plating a sample of cells onto medium that lacks the required nutrient.
|
From page 86... ...
, and ultimately with a mechanism by which the gene product executes the function. Even with the latest in technologies, one still faces problems in associating genes with products and the products with essential functions related to cellular structure, progress of the cell division cycle, or other functions carried out by macromolecular assemblies.
|
From page 87... ...
Isolation of the gene for that protein depends on what is already known about that protein and often on the ingenuity of the investigator. If the protein sequence is known, oligonucleotide probes can be chemically synthesized on the basis of information contained in the protein's amino acid sequence.
|
From page 88... ...
Specific features of transformation vary significantly with the organism. In yeast and in the slime mold Dictyosteli~n, the introduced gene can displace the resident gene by homologous recombination (recombination that requires sequence similarity)
|
From page 89... ...
Specific proteins have been identified that bind adjacent to and perhaps within the coding region of active genes and are necessary for specific gene transcription and function, but many such proteins are as yet uncharacterized. Existing techniques of genetic, chemical, and physical analyses need to be pushed further, and other techniques will need to be invented to yield a dynamic picture of the changes in the structure of the genome during the cell cycle.
|
From page 90... ...
The Major Components of DNA Replication Have Been Determined Although the problem of how a DNA sequence is transmitted in dividing cells was solved conceptually by Watson and Crick in 1953, the elucidation of the actual molecular basis of replication has required considerable time and effort. At many points in the history of the development of the field it appeared that replication was "solved" and that all that was left was to work out the details.
|
From page 91... ...
M Alberts, Cold Spring Harbor Symp.
|
From page 92... ...
Impressive evidence has already accumulated that transcription, translation, RNA processing, and muscle contraction are also organized in this way. Yet, only for bacterial DNA replication is the field so advanced as to have all the components not only defined, but purified in abundance, and in a form allowing reconstitution of the entire process in the test tube.
|
From page 93... ...
A second aspect of the regulation of eukaryotic DNA synthesis needs to be understood. The eukaryotic cell apparently retains the ability to initiate new replication units throughout the S phase, but a region once replicated cannot be replicated again in the same cell cycle.
|
From page 94... ...
A second item for further research is the means by which cells prevent recombination between repeated sequences. Such repetitive DNA is a hallmark of higher eukaryotic cells and presents a potentially devastating opportunity for a homologous recombination system.
|
From page 95... ...
However, several initial successes in targeting have opened the way to a thorough attack on the problem. Site-Specific Recombination Has Been Studiedfor the Past 20 Years and Many Systems Have Been Studied in Depth In the 1960s it became clear that efficient recombination could take place between segments of DNA that lacked sufficient homology to undergo general homologous recombination.
|
From page 96... ...
In the future, structural studies using x-ray diffraction and nuclear magnetic resonance techniques should be able to add atomic details to the understanding of these processes that is being deduced from molecular biological studies. In contrast to the conservative reactions (no DNA replication)
|
From page 97... ...
Detailed analysis of complex proteins such as these are needed to provide models for systems that lack sophisticated genetics. Major Opportunities Exist to Study DNA Repair in Eukaryotes Yeast can be used to explore uniquely eukaryotic aspects of DNA repair, such as the relationship of DNA repair processes to the cell cycle and the effect of chromatin on DNA repair.
|
From page 98... ...
Furthermore, to date, no one has succeeded in cloning genes that complement the DNA repair deficiencies of these naturally occurring mutants. Problems unique to higher organisms that will need to be addressed include the relative DNA repair capabilities of different types of differentiated cells and the DNA repair capabilities of germline cells versus somatic cells.
|
From page 99... ...
Genes that are moved onto the inactivated X chromosome are also inactivated: This type of gene inactivation does not generally occur when a gene is simply moved near a member of a coordinately controlled gene set. Formation of Primary RNA Transcripts Depends on Specific DNA Signals For a gene to be transcribed, it must have certain nucleotide sequences arranged in serial order along the DNA chain.
|
From page 100... ...
That is, specific DNA-binding proteins may recognize and bind with a similar nucleotide sequence present in the promoter region or enhancer of a number of different genes. In this way, a particular set of genes typical of a certain cell type would be activated or inhibited in a coordinated, programmatic fashion by the activation of a specific type of DNA-binding protein.
|
From page 101... ...
Catalytic RNAs are now thought to have been common in primitive biological systems and still to be integral to many contemporary processes (such as protein synthesis)
|
From page 102... ...
The basis of this "imprinting" is not known, but data suggest that specific methylation changes that occur during the formation of egg and sperm may be involved. Although DNA methylation could explain the heritable patterns of gene expression displayed by various cell lineages in multicellular organisms, we do not know how large a role methylation plays, nor do we know what controls the patterns of DNA modification.
|
From page 103... ...
Restriction Fragment Length Polymorphism DNA Markers Have Increased the Power of Mendelian Techniques for Mapping Genes RFLPs are naturally occurring variants in the nucleotide sequence of DNA that can be used as genetic markers. They are transmitted from one generation to the next in the same way as the genes that govern eye or flower color.
|
From page 104... ...
. In contrast, eukaryotic cells, such as those of animals and plants, have, in addition to their plasmalemma, at least a dozen different types of chemically specific membranes that create separate intracellular compartments with different microenvironments required by
|
From page 105... ...
In more complex multicellular organisms, it is also needed for the production of proteins destined for export out of the cell, such as enzymes, hormones, growth factors, blood proteins, antibodies, or components of the extracellular matrix. In all cells, proteins are synthesized on ribosomes, which translate into amino acid sequences the instructions received from active genes in the form of mRNAs.
|
From page 106... ...
In eukaryotic cells, ribosomes and protein synthesis occur primarily in the cytosol, to which mRNAs have direct access from the nucleus and in which the pool of amino acids and all ancillary factors required for protein synthesis are located. Only 2 percent of the total protein production is accounted for by small mitochondrial ribosomes whose products are used exclusively in mitochondria.
|
From page 107... ...
The amino acid sequence of the signal that directs certain proteins to the nucleus is known in a few cases, but the corresponding receptor remains to be identified. A substantial body of information already exists about traffic regulation of proteins targeted to mitochondrial and chloroplast membranes.
|
From page 108... ...
The origin and evolution of the mitochondrion are linked to the origin and evolution of eukaryotic cells. Understanding of mitochondrial function in turn sheds light on a wide array of fundamental and practical issues, ranging from certain metabolic and genetic diseases to evolution itself.
|
From page 109... ...
Excellent Opportunities Exist to Study the Mechanisms of Expression and Replication of Mitochondrial DNA Studies of the enzymes and ancillary proteins responsible for mitochondrial DNA replication, DNA transcription into RNA, and RNA processing to mature RNA species are making rapid progress, aided by the development of soluble in vitro preparations derived from broken mitochondria and by the use of recombinant DNA technologies. Specific proteins have already been identified and, in some cases, isolated in partially or completely pure form.
|
From page 110... ...
After their synthesis on cytoplasmic ribosomes, the nuclear gene-coded polypeptides are imported to their correct location within the mitochondrion. Biochemical studies and the application of recombinant DNA technology have shown that proteins destined for one of the three innermost compartments are usually made from precursors with extensions at the amino-terminal end; these extensions can be as long as 100 amino acids and function as signals directing the proteins to the proper location.
|
From page 111... ...
Without cellular motility, white blood cells would neither accumulate at sites of inflammation nor ingest invading microorganisms. Without active and rapid movements of organelles in axons and large plant cells, the peripheral parts of these cells would not be nourished.
|
From page 112... ...
Recent physical studies on purified cytoskeletal fibers and analysis of the mechanical properties of live cells support this conclusion. Other work has shown that some of the glycolytic enzymes bind to actin filaments and that polyribosomes are associated with isolated cytoskeletons.
|
From page 113... ...
Myosin and actin are widely believed to be responsible for many forms of cell movements in addition to muscle contraction. For cytokinesis (the final step in cell division)
|
From page 114... ...
The pursestring-like contraction that splits two daughter cells apart at cell division is an example of a movement in response to an internal stimulus arising from the poles of the mitotic spindle. The rapid locomotion of white blood cells to sites of infection and their ingestion of bacteria are examples of complex movements in response to external signals.
|
From page 115... ...
This is an area of potential collaboration between cell biologists and engineers. CELL MEMBRANE The Cell Membrane Not Only Forms a Protective Surface But Also Receives Chemical Messages from the Environment The outer cell membrane is an extremely thin, sheetlike assembly of lipid and protein molecules that provides a boundary to the cell's body.
|
From page 116... ...
Depending on cell type, these infrastructures are built either for imparting tensile strength to a delicate membrane or for controlling the lateral mobility of transmembrane proteins, which if not restrained would move rapidly in the membrane because of the fluidity of the lipid bilayer. The first type of infrastructure has been studied extensively in the red blood cells of humans, and its molecular components and their mode of assembly are well known.
|
From page 117... ...
Elastic elements allow blood vessels to modulate the pulsatile flow produced by beats of the heart The mysterious loss of elastic fibers during aging has generated a multimillion dollar cosmetic industry to combat wrinkles. The amino acid sequence of elastin in known, but its molecular structure and its association with other molecules in elastic fibers are major research challenges that, when solved, should help explain and perhaps prevent some cardiovascular diseases and effects of aging.
|
From page 118... ...
Evidence is also growing that binding to the matrix modulates cellular physiology. Active work is also being done on specific growth factors that promote the formation of specialized connective tissue such as bone and on other proteins that initiate the formation of the calcium-phosphate crystals that make bone hard.
|
From page 119... ...
Controls that integrate growth with division occur in the first growth phase of the cell cycle, called G1 in yeast and animal cells. Although many of the components of this control system have been identified in yeast, the links between nutrition, protein synthesis, and the apparatus for cell division remain unknown even for this unicellular organism.
|
From page 120... ...
In addition, cells in general and epithelial cells in particular participate in shortrange interactions with the newly formed extracellular matrix. These interactions are mediated by mutual recognition between cell membrane receptors and specific parts of matrix proteins.
|
From page 121... ...
Modulations in the construction of junctional complexes also control the permeability of epithelia in the intestine, lung, and kidney as well as the permeability of the vascular endothelium. Long-Range Communication Requires Messenger Molecules and Receptors As embryonic development progresses, mechanisms of short-range communication are extended and diversified, but long-range interactions through hormones and growth factors become progressively more important.
|
From page 122... ...
Until the advent of genetic engineering, studies were limited to those factors available in sufficient quantity from biological sources. Much early work was done with three growth factors: erythropoietin, a glycoprotein from the kidney that stimulates red blood cell production from a common stem cell progenitor of both red and white blood cells; nerve growth factor (NGF)
|
From page 123... ...
Receptors There May Be Even More Receptor Proteins Than Messenger Molecules Receptors are protein molecules that bind specific hormones or growth factors and relay a signal that converts an extracellular message into a biochemical action inside the cell. There may be more kinds of receptors than messenger molecules because the receptors for a single messenger molecule can be different on different types of cells.
|
From page 124... ...
(Cold Spring Harbor Press, Cold Spring Harbor, N.Y., in press) , chapter 3]
|
From page 125... ...
The patch clamp reveals that ion channels are present in the plasma membrane of all eukaryotic cells, not only excitable cells like nerves and muscle. Because this ubiquity was not previously suspected, an important task is to determine what roles these signaling molecules play in the housekeeping functions and daily life of cells outside the nervous system.
|
From page 126... ...
~ugates.~:~Alter-~:~::~:~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ :~ :: ~ ~ ~.~ ~ ~ .:~y~:~some~:~:roor~:tells:~m~express:~un~s~6nti¢Qn~s~.~For~:~ ,~. A, ~ ~ ~ ~ ~: :~ ply ~ ~exp~res~s~n~ Woof ~:~:~th~e~fetal For m: ~:~a:~::~pto~r :~ so:m~lm es ~ occurs in ~ if: ~: :: :: ~ ~ ~therape~utlc:~ap~oach.~ ~ Bus ~ ~we~::~:h~a9Q~ New ~oppo:~r tu r~ies~to~:~test~:~th:es~e~: Hi- ~:~:~ :~:: I::::: :::::::::: ::: :::::: :: :: ::: :::: ::: :: ::: :: ::::::: : : ~:::::::: I: : :: :::::::: :: :: :::: : ::::::: : : ~ ~ poll yeses Do ~ op~:~ette~r:~straten'es~:'or~u I~ Nice ~:~s~u~rtace ~:~:~Iow~Tarcetlrl~:~soeenic~Is~Io~r:~orua~aellPvew.:~:~ :~ ::: :~ :::: if: ~ ::: : Captors to: ~:~ : ~ ::: ~: : ~ : ~ :: ~:~ :~:: : ~ :: I: :~ :: ::: : :::: ::~: :~ ~::::~:::: : : :: :: :~ ~ ~ I:::: ~ :::: : : :: ~ ~ :: : : : :~ ~ ~ Because ion channels are large, exposed macromolecules having important functions, they have become the target of many classes of natural toxins and of many clinically active drugs.
|
From page 127... ...
and the parasympathetic neurotransmitter (ACh) act on several classes of membrane receptors to produce several intracellular second messengers, which in turn modulate the activities of a variety of ion channels.
|
From page 128... ...
Studies indicate that odorant stimuli activate adenyl cyclase in the olfactory epithelium of the nose, suggesting that cyclic AMP is also the intracellular second messenger that mediates the sense of smell. More recently, biochemical and genetic studies of the regulation of cyclic AMP synthesis led to the discovery of Gc, a membrane protein that couples hormone receptors to stimulation of adenyl cyclase.
|
From page 129... ...
and protein kinase C, act on other cellular components to produce a set of responses that includes contraction of smooth muscle (stimulated by agents such as norepinephnne) , modulation of synaptic responses in the central nervous system, a variety of secretory responses, and some, but not all, proliferative responses of cells to growth factors such as PDGF.
|
From page 130... ...
Only a few years ago, scientists would have scoffed at the notion that studies of bacterial protein synthesis or retinal phototransduction could reveal anything useful about the cause of cancer. In addition to explaining the cellular actions of a number of important hormones and growth factors, the cascade of events elicited by these substrates has made two other general contributions to the understanding of signal transduction.
|
From page 131... ...
Many endocrine responses mediated by cyclic AMP are only mildly affected in PUPA resistance to parathyroid hormone, the master hormone of calcium ion homeostasis, is a prominent feature of PHP-I, suggesting that the amount or activity of Gs is normally more rate-limiting for actions of this hormone than of others.
|
From page 132... ...
Cytoplasrruc Free Calcium Acts as a Second Messenger Three mechanisms for raising the free calcium ion concentration in cytoplasm have been found: the voltage-gated calcium channel of the plasma membrane, release of calcium ions from the endoplasmic reticulum of muscle when the surface membrane is depolarized in response to a nerve impulse, and release of calcium ions from the endoplasmic reticulum in response to hormonal signals acting on plasma membrane receptors. We understand how {P3 iS produced, but not what it does to the endoplasmic reticulum to release calcium.
|
From page 133... ...
other oncogenes are related to growth factors or to their transmembrane receptors; (3) the ras gene proteins bind and hydrolyze GTP and seem to act as signal transducers at the plasma membrane and cytoplasm; and (4)
|
From page 134... ...
, thus greatly complicating protein targeting and the integration of genome expression. Other research is focused on the plant's rigid cell walls, which are constituted in different ways at different stages of development and for various specific functions of different cell types.
|
From page 135... ...
As more and more chloroplast DNA is sequenced, interest will grow in identifying the gene products of unrecognized proteins; their identification should move us toward a better understanding of photosynthesis and plastic metabolism. This DNA sequencing will also reveal features of plastic genes.
|
From page 136... ...
A second possibility, favored by most available evidence, is that the major organelles characteristic of eukaryotic cells-mitochondria (which are found in the cells of all but a very few eukaryotes) and chloroplast~are the descendants of symbiotic bacteria that entered early eukaryotic cells.
|
From page 137... ...
of Plants Is Crucial to Understanding [low Plants Grow Lacking a skeletal structure and subjected to a fluctuating osmotic environment, plant cells rely on rigid cell walls to serve as cementing substances between cells, to provide mechanical strength, and to support high internal osmotic pressures. For many years, it has been known that the ultimate shape and strength of such walls are largely determined by the pattern and extent of deposition of extended fibrils composed of cellulose (glucose molecules joined in p-1,4 linkage)
|
From page 138... ...
Exciting progress has been made recently for the cell-wall protein extensin, since a gene for this protein has recently been cloned and characterized. Coupled with previous structural information on the protein, data from the gene sequence now give the entire amino acid sequence of the protein so that we can identify sites of glycosylation, crosslinking, and possible areas of interaction of this polymer with other wall components.
|
From page 139... ...
Since plant cell walls are a major sink for biomass, much of which is only poorly digestible, it is hoped that our ultimate ability to modify wall structure by modifying the expression of genes controlling wall assembly will lead to a greater understanding of just how flexible such wall structure can be, and perhaps also to the development of plants with improved agronomic or nutritional value.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.