The Genome Is Packaged into Chromosomes and Replicated During Cell Divison

• Most of the DNA in eukaryotic cells is located in the nucleus, extensively folded into the familiar structures we know as chromosomes

• Each chromosome contains a single linear DNA molecule associated with certain proteins

• In prokaryotic cells, most or all of the genetic information resides in a single circular DNA molecule about a millimeter in length; this molecule lies, folded back on itself many times, in the central region of the cell

• The genome of an organism comprises its entire complement of DNA

• With the exception of eggs and sperm, every normal human cell has 46 chromosomes

• Every time a cell divides, a large multiprotein replication machine, the replisome, separates the two strands of double-helical DNA in the chromosomes and uses each strand as a template to assemble nucleotides into a new complementary strand

• The outcome is a pair of double helices, each identical to the original

• DNA polymerase, which is responsible for linking nucleotides into a DNA strand

• The molecular design of DNA and the remarkable properties of the replisome assure rapid, highly accurate copying

• Many DNA polymerase molecules work in concert, each one copying part of a chromosome

• The entire genome of fruit flies, about 1.2 x 108 nucleotides long, can be copied in three minutes (a very short time)

• Because of the accuracy of DNA replication, nearly all the cells in our bodies carry the same genetic instructions

• A rather dramatic example of gene control involves the inactivation of an entire chromosome in human females

• Women have two X chromosomes, whereas men have one

• X chromosome and one Y chromosome, which has different genes than the X chromosome

• Yet the genes on the X chromosome must, for the most part, be equally active in female cells (XX) and male cells (XY)

• To achieve this balance, one of the X chromosomes in female cells is chemically modified and condensed into a very small mass called a Barr body, which is inactive and never transcribed

• We inherit a small amount of genetic material entirely and uniquely from our mothers

• This is the circular DNA present in mitochondria, the organelles in eukaryotic cells that synthesize ATP using the energy released by the breakdown of nutrients

• Mitochondria contain multiple copies of their own DNA genomes, which code for some of the mitochondrial proteins

• Because each human inherits mitochondrial DNA only from his or her mother (it comes with the egg but not the sperm), the distinctive features of a particular mitochondrial DNA can be used to trace the maternal history

• Chloroplasts, the organelles that carry out photosynthesis in plants, also have their own circular genomes

Mutation May Be Good, Bad, or Indifferent

• Mistakes occasionally do occur spontaneously during DNA replication, causing changes in the sequence of nucleotides

• Such changes, or mutations, also can arise from radiation that causes damage to the nucleotide chain or from chemical poisons, such as those in cigarette smoke, that lead to errors during the DNA-copying process

• Mutations come in various forms: a simple swap of one nucleotide for another; the deletion, insertion, or inversion of one to millions of nucleotides in the DNA of one chromosome; and translocation of a stretch of DNA from one chromosome to another

• In sexually reproducing animals like ourselves, mutations can be inherited only if they are present in cells that potentially contribute to the formation of offspring

• Such germ-line cells include eggs, sperm, and their precursor cells

• Body cells that do not contribute to offspring are called somatic cells

• Mutations that occur in these cells never are inherited, although they may contribute to the onset of cancer

• Plants have a less distinct division between somatic and germ-line cells since many plant cells can function in both capacities

• Mutated genes that encode altered proteins or that can’t be controlled properly cause numerous inherited diseases

• The single amino acid change caused by the sickle cell mutation reduces the ability of red blood cells to carry oxygen from the lungs to the tissues

• Recent advances in detecting disease-causing mutations and in understanding how they affect cell functions offer exciting possibilities for reducing their often devastating effects

• Sequencing of the human genome has shown that a very large proportion of our DNA does not code for any RNA or have any discernible regulatory function, a quite unexpected finding

• Mutations in these regions usually produce no immediate effects—good or bad

• Such “indifferent” mutations in nonfunctional DNA may have been a major

• The player in evolution, leading to the creation of new genes or new regulatory sequences for controlling already existing genes

• For instance, since binding sites for transcription factors typically are only 10–12 nucleotides long, a few single-nucleotide mutations might convert a nonfunctional bit of DNA into a functional protein-binding regulatory site

• Much of the nonessential DNA in both eukaryotes and prokaryotes consist of highly repeated sequences that can move from one place in the genome to another

• These mobile DNA elements can jump (transpose) into genes, most commonly damaging but sometimes activating them

• Jumping generally occurs rarely enough to avoid endangering the host organism

• Mobile elements, which were discovered first in plants, are responsible for leaf color variegation and the diverse beautiful color patterns of Indian corn kernels

• By jumping in and out of genes that control pigmentation as plant development progresses, the mobile elements give rise to elaborate colored patterns

• Mobile elements were later found in bacteria which they often carry and, unfortunately, disseminate genes for antibiotic resistance

• Now we understand that mobile elements have multiplied and slowly accumulated in genomes over evolutionary time, becoming a universal property of genomes in present-day organisms

• They account for an astounding 45 percent of the human genome

• Some of our own mobile DNA elements are copies—often highly mutated and damaged—of genomes from viruses that spend part of their life cycle as DNA segments inserted into host-cell DNA

• Thus we carry in our chromosomes the genetic residues of infections acquired by our ancestors

• Once viewed only as molecular parasites, mobile DNA elements are now thought to have contributed significantly to the evolution of higher organisms

1.3 - The Work of Cells

• In essence, any cell is simply a compartment with a watery interior that is separated from the external environment by a surface membrane (the plasma membrane) that prevents the free flow of molecules in and out of cells

• In addition, as we’ve noted, eukaryotic cells have extensive internal membranes that further subdivide the cell into various compartments, the organelles

• The plasma membrane and other cellular membranes are composed primarily of two layers of phospholipid molecules

• These bipartite molecules have a “water-loving” (hydrophilic) end and a “water-hating” (hydrophobic) end

• The two phospholipid layers of a membrane are oriented with all the hydrophilic ends directed toward the inner and outer surfaces and the hydrophobic ends buried within the interior

• Smaller amounts of other lipids, such as cholesterol, and many kinds of proteins are inserted into the phospholipid framework

• The lipid molecules and some proteins can float sidewise in the plane of the membrane, giving membranes a fluid character

• This fluidity allows cells to change shape and even move

• The attachment of some membrane proteins to other molecules inside or outside the cell restricts their lateral movement

• The cytosol and the internal spaces of organelles differ from each other and from the cell exterior in terms of acidity, ionic composition, and protein contents

• The unique functions and micro-climates of the various cell compartments are due largely to the proteins that reside in their membranes or interior

• We can think of the entire cell compartment as a factory dedicated to sustaining the well-being of the cell

• Much cellular work is performed by molecular machines, some housed in the cytosol and some in various organelles

Cells Build and Degrade Numerous Molecules and Structures

• As chemical factories, cells produce an enormous number of complex molecules from simple chemical building blocks

• All of this synthetic work is powered by chemical energy extracted primarily from sugars and fats or sunlight, in the case of plant cells, and stored primarily in ATP, the universal “currency” of chemical energy

• In animal and plant cells, most ATP is produced by large molecular machines located in two organelles, mitochondria, and chloroplasts

• Similar machines for generating ATP are located in the plasma membrane of bacterial cells

• Both mitochondria and chloroplasts are thought to have originated as bacteria that took up residence inside eukaryotic cells and then became welcome collaborators

• Directly or indirectly, all of our food is created by plant cells using sunlight to build complex macromolecules during photosynthesis

• Even underground oil supplies are derived from the decay of plant material

• Cells need to break down worn-out or obsolete parts into small molecules that can be discarded or recycled

• This housekeeping task is assigned largely to lysosomes, organelles crammed with degradative enzymes

• The interior of lysosomes has a pH of about 5.0, roughly 100 times more acidic than that of the surrounding cytosol

• This aids in the breakdown of materials by lysosomal enzymes, which are specially designed to function at such a low pH

• To create the low pH environment, proteins located in the lysosomal membrane pump hydrogen ions into the lysosome using energy supplied from ATP

• Lysosomes are assisted in the cell’s cleanup work by peroxisomes, these small organelles are specialized for breaking down the lipid components of membranes and rendering various toxins harmless

• Most of the structural and functional properties of cells depend on proteins, thus for cells to work properly, the numerous proteins composing the various working compartments must be transported from where they are made to their proper locations

• Some proteins are made on ribosomes that are free in the cytosol

• Proteins are secreted from the cell and most membrane proteins are made on ribosomes associated with the endoplasmic reticulum (ER)

• This organelle produces, processes, and ships out both proteins and lipids

• Protein chains produced on the ER move to the Golgi apparatus, where they are further modified before being forwarded to their final destinations

• Proteins that travel in this way contain short sequences of amino acids or attached sugar chains (oligosaccharides) that serve as addresses for directing them to their correct destinations

• These addresses work because they are recognized and bound by other proteins that do the sorting and shipping in various cell compartments

Animals Cells Produce Their Own External Environment and Glues

• The simplest multicellular animals are single cells embedded in a jelly of proteins and polysaccharides called the extracellular matrix

• Cells themselves produce and secrete these materials, thus creating their own immediate environment

• Collagen, the single most abundant protein in the animal kingdom, is a major component of the extracellular matrix in most tissues

• In animals, the extracellular matrix cushions and lubricates cells

• A specialized, especially tough matrix, the basal lamina, forms a supporting layer underlying sheet-like cell layers and helps prevent the cells from ripping apart

• The cells in animal tissues are “glued” together by cell-adhesion molecules (CAMs) embedded in their surface membranes

• Some CAMs bind cells to one another; other types bind cells to the extracellular matrix, forming a cohesive unit

• The cells of higher plants contain relatively few such molecules; instead, plants cells are rigidly tied together by the extensive interlocking of the cell walls of neighboring cells

• The cytosols of adjacent animal or plant cells often are connected by functionally similar but structurally different “bridges” called gap junctions in animals and plasmodesmata in plants

• These structures allow cells to exchange small molecules including nutrients and signals, facilitating coordinated functioning of the cells in a tissue

Cells Change Shape and Move

• Although cells sometimes are spherical, they more commonly have more elaborate shapes due to their internal skeletons and external attachments

• Three types of protein filaments, organized into networks and bundles, form the cytoskeleton within animal cells

• The cytoskeleton prevents the plasma membrane of animal cells from relaxing into a sphere it also functions in cell locomotion and the intracellular transport of vesicles, chromosomes, and macromolecules

• The cytoskeleton can be linked through the cell surface to the extracellular matrix or to the cytoskeleton of other cells, thus helping to form tissues

• All cytoskeletal filaments are long polymers of protein subunits

• Elaborate systems regulate the assembly and disassembly of the cytoskeleton, thereby controlling cell shape

• In some cells, the cytoskeleton is relatively stable, but in others, it changes shape continuously

• Shrinkage of the cytoskeleton in some parts of the cell and its growth in other parts can produce coordinated changes in shape that result in cell locomotion

• As this process continues due to coordinated changes in the cytoskeleton, the cell moves forward

• Cells can move at rates on the order of 20 m/second

• Cell locomotion is used during the embryonic development of multicellular animals to shape tissues and during adulthood to defend against infection, transport nutrients, and heal wounds

• This process doesn't play a role in the growth and development of multicellular plants because new plant cells are generated by the division of existing cells that share cell walls

• Resulting in plant development involves cell enlargement but not the movement of cells from one position to another

Cells Sense and Send Information

• A living cell continuously monitors its surroundings and adjusts its own activities and composition accordingly

• They communicate by deliberately sending signals that can be received and interpreted by other cells

• Such signals are common not only within an individual organism but also between organisms

• The signals employed by cells include simple small chemicals, gases, proteins, light, and mechanical movements

• Cells possess numerous receptor proteins for detecting signals and elaborate pathways for transmitting them within the cell to evoke a response

• At any time, a cell may be able to sense only some of the signals around it, and how a

• The cell that responds to a signal may change with time

• In some cases, receiving one signal primes a cell to respond to a subsequent different signal in a particular way

• Both changes in the environment (e.g., an increase or decrease in a particular nutrient or the light level) and signals received from other cells represent external information that cells must process

• The most rapid responses to such signals generally involve changes in the location or activity of pre-existing proteins

• The rise in blood glucose is sensed by cells in the pancreas, which respond by releasing their stored supply of the protein hormone insulin

• The circulating insulin signal causes glucose transporters in the cytoplasm of fat and muscle cells to move to the cell surface, where they begin importing glucose

• Meanwhile, liver cells also are furiously taking in glucose via a different glucose transporter

• In both liver and muscle cells, an intracellular signaling pathway triggered by binding of insulin to cell-surface receptors activates a key enzyme needed to make glycogen, a large glucose polymer

• The net result of these cell responses is that your blood glucose level falls and extra glucose is stored as glycogen, which your cells can use as a glucose source when you skip a meal to cram for a test

• The ability of cells to send and respond to signals is crucial to the development

• Many developmentally important signals are secreted proteins produced by specific cells at specific times and places in a developing organism

• Often a receiving cell integrates multiple signals in deciding how to behave, for example, to differentiate into a particular tissue type, to extend a process, to die, to send back a confirming signal, or to migrate

• The functions of about half the proteins in humans, roundworms, yeast, and several other eukaryotic organisms have been predicted based on analyses of genomic sequences

• Such analyses have revealed that at least 10–15 percent of the proteins in eukaryotes function as secreted extracellular signals, signal receptors, or intracellular signal-transduction proteins, which pass along a signal through a series of steps culminating in a particular cellular response (e.g., increased glycogen synthesis)

• Clearly, signaling and signal transduction are major activities of cells

Cells Regulate Their Gene Expression to Meet Changing Needs

• To modulate the activities of existing proteins, cells often respond to changing circumstances and to signals from other cells by altering the amount or types of proteins they contain

• Gene expression, the overall process of selectively reading and using genetic information, is commonly controlled at the level of transcription, the first step in the production of proteins

• Cells can produce a particular mRNA only when the encoded protein is needed, thus minimizing wasted energy

• Producing an mRNA is the first and only in a chain of regulated events that together determine whether an active protein product is produced from a particular gene

• E. coli cells prefer glucose as a sugar source, but they can survive on lactose in a pinch

• These bacteria use both a DNA-binding repressor protein and a DNA-binding activator protein to change the rate of transcription of three genes needed to metabolize lactose depending on the relative amounts of glucose and lactose present

• Such dual positive/negative control of gene expression fine-tunes the bacterial cell’s enzymatic equipment for the job at hand

• Like bacterial cells, unicellular eukaryotes may be subjected to widely varying environmental conditions that require extensive changes in cellular structures and function

• In multicellular organisms, the environment around most cells is relatively constant

• The major purpose of gene control in us and in other complex organisms is to tailor the properties of various cell types to the benefit of the entire animal or plant

• Control of gene activity in eukaryotic cells usually involves a balance between the actions of transcriptional activators and repressors

• The binding of activators to specific DNA regulatory sequences called enhancers turns on transcription, and binding of repressors to other regulatory sequences called silencers turns off transcription

• Rarely, expression of a particular gene could occur only in part of the brain, only during evening hours, only during a certain stage of development, only after a large meal, and so forth

• Many external signals modify the activity of transcriptional activators and repressors that control specific genes

• Hormone binding changes the shape of the receptor so that it can bind to specific enhancer sequences in the DNA, thus turning the receptor into a transcriptional activator

• By this rather simple signal-transduction pathway, steroid hormones cause cells to change which genes they transcribe

• Since steroid hormones can circulate in the bloodstream, they can affect the properties of many or all cells in a temporally coordinated manner

• The binding of many other hormones and of growth factors to receptors on the cell surface triggers different signal-transduction pathways that also lead to changes in the transcription of specific genes

• These pathways involve multiple components and are more complicated than those transducing steroid hormone signals, the general idea is the same

Cells Grow and Divide

• The most remarkable feature of cells and entire organisms is their ability to reproduce

• Biological reproduction, with continuing evolutionary selection for a highly functional body plan, is why today’s horseshoe crabs look much as they did 300 million years ago

• The Teton Mountains in Wyoming, now about 14,000 feet high and still growing, didn't exist a mere 10 million years ago

• Yet horseshoe crabs, with a life span of about 19 years, have faithfully reproduced their ancient selves more than half a million times during that period

• The common impression that biological structure is transient and geological structure is stable is the exact opposite of the truth

• Despite the limited duration of our individual lives, reproduction gives us a potential for immortality that a mountain or a rock does not have

• The simplest type of reproduction entails the division of a “parent” cell into two “daughter” cells

• This occurs as part of the cell cycle, a series of events that prepares a cell to divide followed by the actual division process, called mitosis

• The eukaryotic cell cycle commonly is represented as four stages

• The chromosomes and the DNA they carry are copied during the S (synthesis) phase

• The replicated chromosomes separate during the M (mitotic) phase, with each daughter cell getting a copy of each chromosome during cell division

• The M and S phases are separated by two gap stages, the G1 phase and G2 phase, during which mRNAs and proteins are made

• In single-celled organisms, both daughter cells often (though not always) resemble the parent cell

• In multicellular organisms, stem cells can give rise to two different cells, one that resembles the parent cell and one that does not

• Such asymmetric cell division is critical to the generation of different cell types in the body

• During growth, the cell cycle operates continuously, with newly formed daughter cells immediately embarking on their own path to mitosis

• With optimal conditions, bacteria can divide to form two daughter cells once every 30 minutes

• With this rate, in an hour one cell becomes four; in a day one cell becomes more than 1014, which if dried would weigh about 25 grams

• Under normal circumstances, growth cannot continue at this rate because the food supply becomes limiting

• Most eukaryotic cells take longer than bacterial cells to grow and divide

• The cell cycle in adult plants and animals normally are highly regulated

• This tight control prevents imbalanced, excessive growth of tissues while assuring that worn-out or damaged cells are replaced and that additional cells are formed in response to new circumstances or developmental needs

• The fundamental defect in cancer is the loss of the ability to control the growth and division of cells

• Mitosis is an asexual process since the daughter cells carry the exact same genetic information as the parental cell

• In sexual reproduction, the fusion of two cells produces a third cell that contains genetic information from each parental cell

• Since such fusions would cause an ever-increasing number of chromosomes, sexual reproductive cycles employ a special type of cell division, called meiosis, that reduces the number of chromosomes in preparation for fusion