HOW AND WHY GENES ARE REGULATED

           Every somatic cell in an organism contains identical genetic instructions.

            They all share the same genome.

            So what makes cells different from one another?

           In cellular differentiation, cells become specialized in

            structure and

            function.

           Certain genes are turned on and off in the process of gene regulation.

Patterns of Gene Expression in Differentiated Cells

           In gene expression,

            a gene is turned on and transcribed into RNA and

            information flows from

             genes to proteins and
             genotype to phenotype.

           Information flows from DNA to RNA to proteins.

           The great differences among cells in an organism must result from the selective expression of genes.

Gene Regulation in Bacteria

           Natural selection has favored bacteria that express

            only certain genes

            only at specific times when the products are needed by the cell.

           So how do bacteria selectively turn their genes on and off?

           An operon includes

            a cluster of genes with related functions and

            the control sequences that turn the genes on or off.

           The bacterium E. coli uses the lac operon to coordinate the expression of genes that produce enzymes used to break down lactose in the bacteriums environment.

           The lac operon uses

            a promoter, a control sequence where the transcription enzyme attaches and initiates transcription,

            an operator, a DNA segment that acts as a switch that is turned on or off, and

            a repressor, which binds to the operator and physically blocks the attachment of RNA polymerase and transcription.

Gene Regulation in Eukaryotic Cells

           Eukaryotic cells have more complex gene regulating mechanisms with many points where the process can be turned on or off.

           The multiple mechanisms that control gene expression are like the many control valves along a water supply.

The Regulation of DNA Packing

           Cells may use DNA packing for long-term inactivation of genes.

           X chromosome inactivation

            takes place early in embryonic development,

            occurs in female mammals, and

            is when one of the two X chromosomes in each cell is inactivated at random.

           All of the descendants of each cell will have the same X chromosome turned off.

           If a female is heterozygous for a gene on the X chromosome,

            about half her cells will express one allele and

            the others will express the alternate allele.

The Initiation of Transcription

           The initiation of transcription is the most important stage for regulating gene expression.

           In prokaryotes and eukaryotes, regulatory proteins

            bind to DNA and

            turn the transcription of genes on and off.

           Transcription in eukaryotes, unlike in prokaryotes, is complex, involving many proteins, called transcription factors, that bind to DNA sequences called enhancers.

           Repressor proteins called silencers

            bind to DNA and

            inhibit the start of transcription.

           Activators

            are more typically used by eukaryotes than silencers and

            turn genes on by binding to DNA.

RNA Processing and Breakdown

           The eukaryotic cell

            localizes transcription in the nucleus and

            processes RNA in the nucleus.

           RNA processing includes the

            addition of a cap and tail to the RNA,

            removal of any introns, and

            splicing together of the remaining exons.

           In alternative RNA splicing, exons may be spliced together in different combinations, producing more than one type of polypeptide from a single gene.

           A typical human gene contains about ten exons, with

            nearly all human genes spliced in at least two different ways and

            some spliced hundreds of different ways!

           Eukaryotic mRNAs

            can last for hours to weeks to months and

            are all eventually broken down and their parts recycled.

microRNAs

           Small single-stranded RNA molecules, called microRNAs (miRNAs), bind to complementary sequences on mRNA molecules in the cytoplasm.

           Some trigger the breakdown of their target mRNA, and others block translation.

           It has been estimated that miRNAs may regulate the expression of up to one-third of all human genes, yet miRNAs were unknown 20 years ago!

The Initiation of Translation

           The process of translation offers additional opportunities for regulation by regulatory molecules.

Protein Activation and Breakdown

           Post-translational control mechanisms in eukaryotes

            occur after translation and

            often involve cutting polypeptides into smaller, active final products.

           The selective breakdown of proteins is another control mechanism operating after translation.

Cell Signaling

           In a multicellular organism, gene regulation can cross cell boundaries.

           A cell can produce and secrete chemicals, such as hormones, that affect gene regulation in another cell.

Homeotic genes

           Master control genes called homeotic genes regulate groups of other genes that determine what body parts will develop in which locations.

           Mutations in homeotic genes can produce bizarre effects.

           Similar homeotic genes help direct embryonic development in nearly every eukaryotic organism examined so far.

DNA Microarrays: Visualizing Gene Expression

           A DNA microarray allows visualization of gene expression.

           The pattern of glowing spots enables the researcher to determine which genes were being transcribed in the starting cells.

           Researchers can thus learn which genes are active

            in different tissues or

            in tissues from individuals in different states of health.

 

CLONING PLANTS AND ANIMALS
The Genetic Potential of Cells

           Differentiated cells

            all contain a complete genome and

            have the potential to express all of an organisms genes.

           Differentiated plant cells can develop into a whole new organism.

           The somatic cells of a single plant can be used to produce hundreds or thousands of identical organisms—clones from a single plant.

           Plant cloning demonstrates that cell differentiation in plants

            is reversible and

            does not cause irreversible changes in the DNA.

           Plant cloning is now used extensively in agriculture.

           Regeneration

            is the regrowth of lost body parts and

            occurs, for example, in the regrowth of the legs of salamanders.

           During regeneration of the leg, cells in the leg stump

            reverse their differentiated state,

            divide, and

            then differentiate again to give rise to a new leg.

Reproductive Cloning of Animals

           Nuclear transplantation involves

            replacing the nucleus of an egg cell with the nucleus from a differentiated cell from an adult body and

            allowing the egg to develop into an adult.

           In 1997, Scottish researchers produced Dolly, a sheep, by replacing the nucleus of an egg cell with the nucleus of an adult somatic cell.

           This procedure is called reproductive cloning, because it results in the birth of a new animal.

Practical Applications of Reproductive Cloning

           Since Dolly, reproductive cloning has been used to clone many species of mammals, including mice, horses, dogs, mules, cows, pigs, rabbits, ferrets, and cats.

           Reproductive cloning has been used to restock populations of endangered species including

            a wild mouflon (a small European sheep),

            a banteng (a Javanese cow),

            a gaur (an Asian ox), and

            gray wolves.

           However, cloning does not increase genetic diversity, which may be essential to long-term species survival.

Human Cloning

           Cloning of mammals

            has heightened speculation about human cloning and

            is very difficult and inefficient.

           Critics raise practical and ethical objections to human cloning.

Therapeutic Cloning and Stem Cells

           The purpose of therapeutic cloning is

            not to produce a viable organism but

            to produce embryonic stem cells.

Embryonic Stem Cells

           Embryonic stem cells (ES cells)

            are derived from blastocysts and

            can give rise to all the specialized cells in the body.

Adult Stem Cells

           Adult stem cells

            are cells in adult tissues and

            generate replacements for some of the bodys cells.

           Unlike embryonic ES cells, adult stem cells

            are partway along the road to differentiation and

            usually give rise to only a few related types of specialized cells.

Umbilical Cord Blood Banking

           Umbilical cord blood

            can be collected at birth,

            contains partially differentiated stem cells, and

            has had limited success in the treatment of a few diseases.

           The American Academy of Pediatrics recommends cord blood banking only for babies born into families with a known genetic risk. 

 

THE GENETIC BASIS OF CANCER

           Cancer is a variety of diseases in which cells

            experience changes in gene expression and

            escape from the control mechanisms that normally limit their growth and division.

Genes That Cause Cancer

           As early as 1911, certain viruses were known to cause cancer.

           Oncogenes are

            genes that cause cancer and

            found in viruses.

Oncogenes and Tumor-Suppressor Genes

           Proto-oncogenes are

            normal genes with the potential to become oncogenes,

            found in many animals, and

            often genes that code for growth factors, proteins that stimulate cell division.

           A cell can acquire an oncogene

            from a virus or

            from the mutation of one of its own proto-oncogenes.

           Tumor-suppressor genes

            inhibit cell division,

            prevent uncontrolled cell growth, and

            may be mutated and contribute to cancer.

           Researchers have identified many mutations in both tumor-suppressor and growth factor genes that are associated with cancer.

The Progression of a Cancer

           Nearly 150,000 Americans will be stricken by cancer of the colon (the main part of the large intestine) this year.

           Colon cancer, like many cancers,

            spreads gradually and

            is produced by more than one mutation.

           The development of a malignant tumor is accompanied by a gradual accumulation of mutations that

            convert proto-oncogenes to oncogenes and

            knock out tumor-suppressor genes.

Inherited Cancer

           Most mutations that lead to cancer arise in the organ where the cancer starts.

           In familial or inherited cancer,

            a cancer-causing mutation occurs in a cell that gives rise to gametes and

            the mutation is passed on from generation to generation.

           Breast cancer

            is usually not associated with inherited mutations and

            in some families can be caused by inherited BRCA1 cancer genes.

 

Cancer Risk and Prevention

           Cancer

            is the second leading cause of death (after heart disease) in most industrialized countries and

            can be caused by carcinogens, cancer-causing agents, found in the environment, including

             tobacco products, alcohol, and ultraviolet light from the sun.

           Exposure to carcinogens

            is often an individual choice and

            can be avoided.

           Some studies suggest that certain substances in fruits and vegetables may help protect against a variety of cancers.