CLASSICAL GENETIC Concept 1. Children resemble their parents.

Since the beginning of human history, people have wondered how traits are inherited from one generation to the next. Although children often look more like one parent than the other, most offspring seem to be a blend of the characteristics of both parents. Centuries of breeding of domestic plants and animals had shown that useful traits speed in horses, strength in oxen, and larger fruits in crops can be accentuated by controlled mating. However, there was no scientific way to predict the outcome of a cross between two particular parents. It wasn't until 1865 that an Augustinian Monk named Gregor Mendel found that individual traits are determined by discrete "factors," later known as genes, which are inherited from the parents. His rigorous approach transformed agricultural breeding from an art to a science. He started with parents of known genetic background to provide a baseline against which to compare patterns of inheritance in the resulting offspring. Then he carefully counted the numbers of individuals showing the various traits in successive generations of offspring.

Concept 2 Genes come in pairs.

Rather than looking at the pea plant as a whole, Mendel focused on seven individual traits that he could readily distinguish. He found that each trait has two alternate forms. For example, seed color can be green or yellow. By analyzing the results of various crosses, Mendel concluded that each alternative form of a trait is specified by alternative forms of a gene. To follow the inheritance of genes from parent to child,Mendel first needed to be sure which genes each parent carried. Since pea plants are naturally self-fertilizing, "pure-bred" strains were readily available. Each strain contained only one form of the gene that determined a trait. Purebred plants with yellow seeds only produced offspring with yellow seeds. Pure-bred plants with green seeds only produced offspring with green seeds. From the results of further experiments, Mendel reasoned that pure-bred plants must have two copies of the same gene for each trait.

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Concept 3 Genes don't blend.

In general, offspring appear to be a mixture of parental characteristics. However, Mendel found that this is not true for the pea plant traits that he chose to study. Pure-bred pea plants when crossed did not produce offspring with blended traits. For example, one might expect that a cross between pure-bred green-seeded and pure-bred yellow-seeded pea plants to produce offspring with seeds of an intermediate green-yellow color. After all, color blending happens when paint is mixed together. However, Mendel found that this cross produced offspring with only one color yellow. No intermediate blends were seen, and the green color seemed to have disappeared.

Concept 4 Some genes are dominant.

Mendel believed that genes behave like atoms that compose a pure substance. Genes can combine in various ways, but always maintain their distinct identities. For example, in a cross between two pure-bred parents with different traits like seed color, the hybrid offspring would have both the gene alternates for green and yellow seed color. Why then do offspring from such a cross have only yellow seeds? Mendel proposed that although both gene alternates are present, there is no blending of color because the gene alternate for yellow is "dominant" over the gene alternate for green. The dominant trait is seen whenever a single copy of its gene is inherited. When he crossed the hybrid offspring, green seeds reappeared in the next generation. Mendel reasoned that the "recessive" green trait is shown only when a copy of the recessive gene form is inherited from each parent.

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Concept 5 Genetic inheritance follows rules.

When Mendel proposed that each trait is determined by a pair of genes, it presented a potential problem. If parents pass on both copies of a gene pair, then offspring would end up with four genes for each trait. Mendel deduced that sex cells sperm and eggs contain only one parental gene of each pair. The half-sets of genes contributed by sperm and egg restore a whole set of genes in the offspring. Mendel found that different gene combinations from the parents resulted in specific ratios of dominant-to-recessive traits. The results of a cross between two hybrid parents each carrying one dominant and one recessive gene were key to his synthesis. For example, a cross between two yellow-seed hybrids produces three times as many yellow seeds as green seeds. This is Mendel's famous 3 to 1 ratio.

Concept 6 Genes are real things.

Mendel published his research, Experiments in Plant Hybridization, in 1865 and sent reprints to prominent scientists in several countries. However, his abstract notion of genes was not appreciated by naturalists of his time who had been trained primarily to observe and categorize living things. Thus, Mendel's work lay fallow until 1900, when three European scientists independently confirmed his results. By that time, there was strong evidence that cells are the basic units of life. Biological stains were developed that highlighted structures within cells including thread-like chromosomes. Different organisms proved to have different numbers of chromosomes, suggesting that they might carry information specific for each life form. This study of the cell and chromosomal behavior was to give Mendel's abstract genetic work the physical context it needed.

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Concept 7 All cells arise from pre-existing cells.

For centuries people accepted the "spontaneous generation" of life from inanimate matter. When this long-standing myth was finally dispelled in the mid-1800s, it became clear that all life must arise from pre-existing life via a process of reproduction. If cells are the fundamental units of life, they too must have a reproductive mechanism that maintains the proper chromosome number in each cell.About a decade after the publication of Mendel's paper,scientists carefully documented the behavior of chromosomes during cell division (mitosis), using dyes to make them visible. First, each chromosome copies itself, and the duplicates line up at the "equator" of the cell. Then, duplicate copies of each chromosome are pulled toward opposite poles. Finally, the cell splits at the equator, producing two new cells with identical sets of chromosomes.

Concept 8 Sex cells have one set of chromosomes; body cells have two.
In sexual reproduction, offspring arise from the union of specialized sex cells a female egg and a male sperm. Just before the rediscovery of Mendel's work, careful studies were made of chromosome behavior during the formation of sex cells (meiosis). First, homologous (like) chromosomes pair up at the cell equator where they actually exchange genetic information. Then, one chromosome from each pair is pulled toward each pole. At the end of this reduction division, each daughter cell receives only one homologous chromosome from each pair, ending up with one set.Meiosis halves the set of chromosome and randomly assorts homologous chromosomes into sex cells. The full chromosome number is restored when sperm and egg unite. This exactly mirrored the behavior of genes as deduced by Mendel three decades earlier.

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Concept 9 Specialized determine gender.

chromosomes

People had long philosophized about the observed differences between males and females of a species. If one considers sex a trait, or set of traits, then it followed that sex is inherited. In 1905, closer study of meiosis revealed the chromosomal basis of gender.Scientists noticed an oddball pair among the homologous chromosomes lined up at the cell equator during reduction division. One chromosome (X) was much bigger than the other (Y). In human beings, this mismatched pair of one X and one Y chromosome is seen exclusively in male cells. A matched pair of X chromosomes is found in female cells. Thus, XX chromosomes determine femaleness, and XY chromosomes determine maleness. Females produce only eggs with X chromosomes; males produce sperm with an X or a Y chromosome.

Concept 10 Chromosomes carry genes.

Thomas Hunt Morgan and his students at Columbia University ushered in the era of modern genetics when they showed the physical basis of heredity. Where Mendel had bred pea plants, the Columbia group studied inheritance in the common fruit fly. Unlike Mendel, who found readily identifiable traits, they spent months searching for a fly with any unique trait that could be studied. Finally they discovered a single white-eyed male fly, which stood out from its normal, red-eyed peers. A cross between the mutant male and a red-eyed female produced only red-eyed offspring. White-eyed mutants reappeared in the following generation the classic pattern of a recessive trait. However, the white-eyed trait was seen exclusively in males of the second generation. They concluded that white-eyed is a sex-linked recessive trait. The gene for eye color must be physically located on the X chromosome.

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Concept 11 Genes get shuffled chromosomes exchange pieces.

when

As Morgan and his coworkers identified more and more inherited traits in fruit flies, they noticed that flies often showed particular combinations of traits. This suggested that certain genes were "linked," and inherited together as a unit. They identified four such units or "linkage groups" equal to the number of paired chromosomes observed under the microscope. This provided further evidence that genes are located on chromosomes.Morgan's group used the phenomenon of linkage to construct maps of the fruit fly chromosomes. They found that linked genes are sometimes separated during meiosis, when the homologous chromosomes exchange pieces. How often a pair of genes are separated provides a measure of the relative distance between them on a chromosome. Distant genes recombine frequently. Nearby genes rarely recombine and are closely linked.

Concept 12 Evolution begins with the inheritance of gene variations.

Key to the theory of evolution by natural selection are new trait variations that arise spontaneously and make an organism more competitive in the struggle for survival. Following publication of Darwin's On the Origin of Species, in 1859, field stations were established where scientists could study the unique characteristics of organisms that had evolved to inhabit different environments. However, field observation could not explain the origin of variation or how new traits are inherited. The new sub-discipline of experimental evolution emerged at the turn of the 20th century with the goal to recreate evolution in controlled experiments with agricultural plants and animals. It soon became clear that mutations in genes are the source of variation and that Mendelian genetics offered a statistical method for analyzing the inheritance of new mutations. By the early 1920's, experimental evolutionists had quietly become the first generation of geneticists.

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Concept 13 Mendelian laws apply to human beings.

Although Mendel's laws were first tested in pea plants and fruit flies, evidence quickly mounted that they applied to all living things. Just as mutations had provided keys to understanding fruit fly genetics, pedigrees of families affected by diseases provided many of the first examples of Mendelian inheritance in humans. Recessive inheritance was first described for the disorders alkaptonuria (1902) and albinism (1903). Among the first dominant disorders discovered were brachydactyly (short fingers, 1905), congenital cataracts (1906), and Huntington's chorea (1913). Duchenne muscular dystrophy (1913), red-green color blindness (1914), and hemophilia (1916) were the first sex-linked disorders. The simple concept of eye color inheritance brown is dominant, blue is recessive was published in 1907; however, scientists now believe that several genes are involved.

Concept 14 Mendelian genetics cannot fully explain human health and behavior.
There was obvious interest in applying Mendel's laws to agriculture. Mendel's ideas were also embraced by the eugenics movement, the goal of which was to improve the human species by better breeding. Eugenicists encouraged marriages between people of "good" genetic stock, and discouraged reproduction of the "genetically unfit." Eugenicists wrongly used simple dominant/recessive schemes to explain complex behaviors and mental illnesses which we now know involvemany genes. They also failed to account for environmental effects on human development. In the United States, restrictive eugenics legislation reflected political and social prejudices, rather than genetic facts. The eugenic description of human life was finally discredited by the horrible consequences of the Nazi quest for racial purity.

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Molecul of Genetic Concept 15 DNA and proteins are key molecules of the cell nucleus.
DNA was discovered as a major chemical of the nucleus at about the same time Mendel and Darwin published their work. However, during the early 1900s, proteins were considered better candidates as molecules able to transmit large amounts of hereditary information from generation to generation. Although DNA was known to be a very large molecule, it seemed likely that its four chemical components wereassembled in a monotonous pattern like a synthetic polymer. Also, no specific cellular function had yet been found for DNA. Proteins, on the other hand, were important as enzymes and structural components of living cells. Proteins were also known to be polymers of numerous amino acids. These polymers are called polypeptides. Most importantly, the 20 amino acid "alphabet" of proteins potentially could be configured into more unique information-carrying structures than the four-letter alphabet of DNA.

Concept 16 One gene makes one protein.

In 1902, Archibald Garrod described the inherited disorder alkaptonuria as an "inborn error of metabolism." He proposed that a gene mutation causes a specific defect in the biochemical pathway for eliminating liquid wastes. The phenotype of the disease dark urine is a reflection of this error. This hypothesis was rigorously proven in 1941 by George Beadle and Edward Tatum, using the simple bread mold Neurospora. First, they found that molds exposed to radiation lose the ability to produce essential nutrients, and this slowed, even stopped the growth of the mold. Then, they found that growth can be restored by providing the mutated mold with a specific supplement. They reasoned that each mutation must inactivate the enzyme (protein) needed to synthesize the nutrient. Thus, one gene carries the directions for making one protein.

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Concept 17 A gene is made of DNA.

In the 1920s, experiments showed that a harmless strain of bacteria can become infectious when mixed with a virulent strain of bacteria that had been killed. The dead bacteria apparently provide some chemical that "transforms" the harmless bacteria to infectious ones. This so-called "transforming principle" appeared to be a gene. A team of scientists led by Oswald Avery at the Rockefeller Institute, rigorously followed up on these experiments in the 1940's. They found that a pure extract of the "transforming principle" was unaffected by treatment with protein-digesting enzymes but was destroyed by a DNA-digesting enzyme. This showed that the transforming principle is DNA and, by extension, a gene is made of DNA. Still, many scientists were slow to accept this clear proof that DNA, not protein, is the genetic molecule.

Concept 18 Bacteria and viruses have DNA too.

Microscopes proved the existence of single-celledbacteria. However, there was debate about whether bacteria had genes and what attributes they may have in common with higher life forms. This debate was settled in the 1940's, when it was discovered that bacteria have sex. During the process of conjugation, genes are exchanged through a mating channel that links two bacteria. Electron microscopy suggested that bacterial viruses carry on a similar process. A virus attaches to a host bacterium and injects its genes through its channel-like tail. In 1952, Alfred Hershey showed that DNA, alone, is responsible for the reproduction of new viruses within an infected cell. This provided undeniable support for Avery's earlier experiments that a gene is made of DNA. It also showed that viruses, as well as bacteria, can be used as models for studying universal principles of genetics.

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Concept 19 The DNA molecule is shaped like a twisted ladder.

Earlier work had shown that DNA is composed of building blocks called nucleotides consisting of a deoxyribose sugar, a phosphate group, and one of four nitrogen bases adenine (A), thymine (T), guanine (G), and cytosine (C). Phosphates and sugars of adjacent nucleotides link to form a long polymer. Other key experiments showed that the ratios of A-to-T and G-to-C are constant in all living things. X-ray crystallography provided the final clue that the DNA molecule is a double helix, shaped like a twisted ladder. In 1953, the race to determine how these pieces fit together in a three-dimensional structure was won by James Watson and Francis Crick at the Cavendish Laboratory in Cambridge, England. They showed that alternating deoxyribose and phosphate molecules form the twisted uprights of the DNA ladder. The rungs of the ladder are formed by complementary pairs of nitrogen bases A always paired with T and G always paired with C.

Concept 20 A half DNA ladder is a template for copying the whole.

Because of the obligatory pairing of adenine-to-thymine and guanine-to-cytosine, Watson and Crick proposed that one half of the DNA ladder serves as a template for recreating the other half during DNA replication. By 1958, two lines of evidence came together to provide proof of this hypothesis. First, an enzyme was discovered DNA polymerase that adds complementary nucleotides to the template provided by a half DNA molecule. Second, an ingenious experiment used nitrogen isotopes to follow the construction of new DNA molecules during successive generations of bacteria. This showed that one strand of each DNA molecule is passed along unchanged to each of two daughter cells. This "conserved" strand acts as the template for DNA polymerase to synthesize a second complementary strand, which completes each new DNA molecule.

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Concept 21 RNA is an intermediary between DNA and protein.

DNA is found mostly in the cell nucleus, but another type of nucleic acid, RNA, is common in the cytoplasm. Watson and Crick proposed that RNA must copy the DNA message in the nucleus and carry it out to the cytoplasm, where proteins are synthesized. Crick also predicted the existence of an "adaptor" molecule that reads the genetic code and selects the appropriate amino acids to add to a growing polypeptide chain. This proposed flow of genetic information from DNA to RNA to protein became known as the "Central Dogma." As it turned out, several types of RNA are involved in the utilization of genetic information. In the nucleus, the DNA code is "transcribed," or copied, into a messenger RNA (mRNA) molecule. In the cytoplasm, the mRNA code is "translated" into amino acids. Translation is orchestrated at the ribosome itself partly composed of RNA with transfer RNA playing the role of adaptor.

Concept 22 DNA words are three letters long.

The genetic code had to be a "language" using the DNA alphabet of A, T, C, and G that produced enough DNA "words" to specify each of the 20 known amino acids. Simple math showed that only 16 words are possible from a two-letter combination, but a three-letter code produces 64 words. Operating on the principle that the simplest solution is often correct, researchers assumed a three-letter code called a codon. Research teams at University of British Columbia and the National Institutes of Health laboriously synthesized different RNA molecules, each a long strand composed of a single repeated codon. Then, each type of synthetic RNA was added to a cell-free translation system containing ribosomes, transfer RNAs, and amino acids. As predicted, each type of synthetic RNA produced a polypeptide chain composed of repeated units of a single amino acid. Several codons are "stop" signals and many amino acids are specified by several different codons, accounting for all 64 three-letter combinations.

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Concept 23 A gene is a discrete sequence of DNA nucleotides.

Mendel described a gene as a discrete unit of heredity that influences a visible trait. Beadle and Tatum defined a gene as the discrete directions for making a single protein, which influences a metabolic trait. Early sequencing efforts showed that proteins are, in turn, long chains of amino acids arranged in a specific order. The triplet genetic code further refined the definition of a gene as a discrete sequence of DNA encoding a protein beginning with a "start" codon and ending with a "stop" codon. Gene analysis took a giant step forward with the discovery of methods to determine the exact sequence of nucleotides that compose a specific gene. DNA sequencing was built upon earlier knowledge of DNA polymerases and cell-free systems for replicating DNA. The chain-termination method, which makes clever use of a "defective" DNA nucleotide, now dominates DNA sequencing technology.

Concept 24 The RNA message is sometimes edited.

Dogma and logic dictated that the mRNA code is a faithful representation of the DNA from which it is transcribed. This exact correspondence between mRNA sequence and DNA sequence was generally upheld in experiments with bacterial cells (prokaryotes).However, inconsistencies surfaced as recombinant-DNA techniques allowed researchers to explore the genes of higher cells (eukaryotes). Then, it was found that mRNA transcripts appeared to be shorter than their corresponding genes. This difference became obvious in electron micrographs of mRNA bound to its complementary DNA template where regions of DNA without corresponding mRNA form loops. In fact, the protein coding information in genes is interrupted by non-coding sequences called introns, which results in "split genes." The entire DNA code is faithfully transcribed into a temporary form of RNA (pre-mRNA), but this is edited in the nucleus to yield a mature mRNA. The process of RNA splicing involves removing non-coding regions, introns, and splicing together adjacent coding regions, exons.

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Concept 25 Some viruses store genetic information in RNA.

DNA was believed to be the sole medium for genetic information storage. Furthermore, Watson and Crick's central dogma assumed that information flowed "one-way" from DNA to RNA to protein. So it came as a surprise when in 1971, it was discovered that some viruses shift their genetic information from RNA to DNA.Even so, these viruses ultimately make proteins in the same way as higher organisms. During infection, the RNA code is first transcribed "back" to DNA then to RNA to protein, according to the accepted scheme. The initial conversion of RNA to DNA going in reverse of the central dogma is called reverse transcription, and viruses that use this mechanism are classified as retroviruses. A specialized polymerase, reverse transcriptase, uses the RNA as a template to synthesize complementary and double-stranded DNA molecule.

Concept 26 RNA was the first genetic molecule.

Experiments in the 1960s showed that messenger RNA has the ability to store genetic information, while transfer and ribosomal RNA have the ability to translate genetic information into proteins. Experiments performed two decades later showed that some RNAs can even act as an enzyme to self-edit their own genetic code! These results raised two questions: 1) Why does RNA play so many roles in the flow of genetic information? 2) Why bother storing genetic information in DNA, if RNA alone could do the job? RNA has great capability as a genetic molecule; it once had to carry on hereditary processes on its own. It now seems certain that RNA was the first molecule of heredity, so it evolved all the essential methods for storing and expressing genetic information before DNA came onto the scene. However, single-stranded RNA is rather unstable and is easily damaged by enzymes. By essentially doubling the existing RNA molecule, and using deoxyribose sugar instead of ribose, DNA evolved as a much more stable form to pass genetic information with accuracy.

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Concept 27 Mutations are changes in genetic information.

The DNA sequences from two individuals of the same species are highly similar differing by only about one nucleotide in 1,000. Each DNA difference results from a mutation ranging from single nucleotide changes, to small repeated units, to larger insertions and deletions. Some mutations generate novel changes that are starting points of evolution, and some are responsible for disease. In humans, the vast majority of mutations occur in DNA regions that do not encode proteins. Most of these are neutral in terms of evolution or health; they have no negative or positive effect. In the 1920s, DNA mutations were first induced in Drosophila using X-rays. Other types of ionizing radiation were also found to produce mutations. Ultraviolet radiation, a component of sunlight, causes specific kinds of DNA damage, including the linking of adjacent thymine nucleotides. Chemicals from a variety of man-made and natural sources are known mutagens. Also, DNA replication, itself, is not perfect and is a source of new mutations.

Concept 28 Some types of mutations are automatically repaired.

Up until the 1950s, most biologists thought that genes were stable units. The notion that DNA could be damaged and then repaired came from researchers who were trying to explain the odd behavior of their microbes. Cultures that were seemingly killed by exposure to ultraviolet light would recover after sitting by a window, and mutants would curiously pop up long after exposure to a mutagen. Investigations of organisms from bacteria to humans have uncovered an army of enzymes poised to repair damage from environmental mutagens or errors in DNA replication. Without these enzymes, DNA damage would cause intolerable levels of mutation. Diseases caused by defective repair enzymes shorten life span, illustrating the central role of DNA repair in survival. But the occasional failure to repair DNA or correct errors in replication is also central to survival because these anomalies exist as mutations, and without mutations evolution would be impossible.

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GENETIC ORGANISATION AND CONTROL Concept 29 chromosome. DNA is packaged in a

Work on cytology in the late 1800s had shown that each living thing has a characteristic set of chromosomes in the nucleus of each cell. During the same period, biochemical studies indicated that the nuclear materials that make up the chromosomes are composed of DNA and proteins. In the first four decades of the 20th century, many scientists believed that protein carried the genetic code, and DNA was merely a supporting "scaffold." Just the opposite proved to be true. Work by Avery and Hershey, in the 1940s and 1950s, proved that DNA is the genetic molecule. Work done in the 1960s and 1970s showed that each chromosome is essentially a package for one very long, continuous strand of the DNA. In higher organisms, structural proteins, some of which are histones, provide a scaffold upon which DNA is built into a compact chromosome. The DNA strand is wound around histone cores, which, in turn, are looped and fixed to specific regions of the chromosome.

Concept 30 Higher cells incorporate an ancient chromosome.

In addition to the set of chromosomes found in the nucleus, a different type of chromosome is found in the energy-generating organelles of the cytoplasm, the mitochondria. The mitochondrial (mt) chromosome contains genes involved in the process of oxidative phosphorylation the production and storage of energy. There is evidence that mitochondria once existed as free-living bacteria, which were taken up by primitive ancestors of eukaryotic cells. The primitive host cell provided a ready source of energy-rich nutrients, and the mitochondrion provided a means to extract energy using oxygen. This symbiotic relationship became key to survival, as oxygen accumulated in the primitive atmosphere. Mitochondria are physically similar in size to bacteria, and the mt genome retains bacteria-like features. Like bacterial chromosomes, the mt genome is a circular molecule. Also, very few introns are found in mt genes. Plants contain an additional ancient chromosome in the chloroplasts, which were also absorbed as symbionts.

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Concept 31 Some DNA does not encode protein.

In most cases when DNA is extracted from living cells, the proteins (including histones) are dissolved away. This results in long strands of naked DNA, which retain their genetic information. So it is useful to visualize a chromosome as a continuous strand of DNA. Arrayed along the DNA strand are the genes, specific regions whose sequences carry the genetic code for making specific proteins. The genes of bacteria are tightly packed together; virtually all the DNA encodes proteins. However, experiments done in the 1960s, showed that a large proportion of eukaryotic DNA is composed of repeated sequences that do not encode proteins. Long noncoding sequences or intergenic regions separate relatively infrequent "islands" of genes. Research in the 1970s showed that numerous non-coding sequences introns are also found within genes, interrupting the protein-coding regions, or exons. It is estimated that only about five percent of human DNA encodes protein.

Concept 32 Some DNA can jump.

Thomas Hunt Morgan's concept of genes as beads along the length of a chromosome changed little through the first half of the 20th century. Genes were seen as inviolate objects with fixed positions on the chromosomes. However, in the 1950s, Barbara McClintock showed that certain DNA fragments, termed transposons, can be activated to transpose ("jump") from one position on a chromosome to another. She hypothesized that transposition provides a means to rapidly reorganize genes in response to environmental stress. McClintock's work was remarkable, not only for the fact that it flew in the face of prevailing dogma, but also because it was based entirely on observation of chromosomes and genetic crosses. Confirmation of her ideas had to await the discovery of the modern tools of DNA analysis. This work paved the way for the modern concept of chromosomes as dynamic, changing structures.

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Concept 33 Genes can be turned on and off.

As researchers untangled the genetic code and the structure of genes in the 1950s and 60s, they began to see genes as a collection of plans, one plan for each protein. But genes do not produce their proteins all the time, suggesting that organisms can regulate gene expression. French researchers first shed light on gene regulation using bacteria. When lactose is available, E. coli turn on an entire suite of genes to metabolize the sugar. Researchers tracked the events lactose initiates and found that lactose removes an inhibitor from the DNA. Removing the inhibitor turns on gene production. The gene that produces the inhibitor is a regulatory gene. Its discovery altered perceptions of development in higher organisms. Cells not only have genetic plans for structural proteins within their DNA, they also have a genetic regulatory program for expressing those plans.

Concept 34 Genes can be moved between species.

Because of the universality of the genetic code, the polymerases of one organism can accurately transcribe a gene from another organism. For example, different species of bacteria obtain antibiotic resistance genes by exchanging small chromosomes called plasmids. In the early 1970s, researchers in California used this type of gene exchange to move a "recombinant" DNA molecule between two different species. By the early 1980s, other scientists adapted the technique and spliced a human gene into E. coli to make recombinant human insulin and growth hormone. Recombinant DNA technology genetic engineering has made it possible to gain insight into how genes work. In cases where it is impractical to test gene function using animal models, genes can first be expressed in bacteria or cell cultures. Similarly, the phenotypes of gene mutations and the efficacy of drugs and other agents can be tested using recombinant systems.

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Concept 35 DNA responds to signals from outside the cell.

Growth and development require that cells communicate with each other and react to signals that come from other parts of the body. Notably, hormones released by various glands travel throughout the body to stimulate the growth of certain cell types. Cells capable of being stimulated by a particular hormone possess a specific receptor anchored in the cell membrane. The binding of a hormone to its receptor initiates a series of molecular transformations, called signal transduction, that relay the growth signal through the cell. First, the receptor transduces the signal through the cell membrane to the internal membrane surface, where it activates protein "messengers." These messengers are part of and initiate a cascade of chemical reactions, often involving the addition of phosphate groups. This is the signal that passes through the cytoplasm and into the nucleus. In the final step of signal transduction, DNA binding proteins attach to regulatory sequences and start DNA replication or transcription.

Concept 36 Different genes are active in different kinds of cells.

Most living things are composed of different kinds of cells specialized to perform different functions. A liver cell, for example, does not have the same biochemical duties as a nerve cell. Yet every cell of an organism has the same set of genetic instructions, so how can different types of cells have such different structures and biochemical functions? Since biochemical function is determined largely by specific enzymes (proteins), different sets of genes must be turned on and off in the various cell types. This is how cells differentiate. This notion of cell-specific expression of genes is upheld by hybridization experiments that can identify the unique mRNAs in a cell type. More recently, DNA arrays and gene chips offer the opportunity to rapidly screen all gene activity of an organism. Co-expression of genes in response to external factors can thus be explored and tested.

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Concept 37 Master genes control basic body plans.

The development of an organism from a fertilized egg, through embryonic and juvenile stages, to adulthood requires the coordinated expression of sets of genes at the proper times and in the proper places. Studies of several bizarre mutations in the fruitfly, Drosophila, provided keys to understanding the molecular basis of large-scale developmental plans. Early embryonic genes express proteins that set up the orientation and define the body segments of the fly embryo. Then "homeotic" genes act on the segments to make the body parts distinct to each segment. Sequence analysis showed that homeotic genes from Drosophila and vertebrate animals share a 180-nucleotide region, called the homeobox. These homeobox proteins have structures highly similar to the regions of regulatory proteins that bind to DNA promoters and enhancers. Thus, a homeotic protein elicits coordinated expression when the protein binds to a specific promoter or enhancer sequence shared by a number of genes involved in the development of body region or segment.

Concept 38 Development growth and death.

balances

cell

In a biological sense, growth results from the reproduction of new cells from pre-existing ones, by the process of cell division (mitosis). Once a tissue or organ reaches an appropriate size, mitosis slows and cells enter a resting phase. This cell cycle of growth and rest is controlled by "checkpoint" molecules first characterized in the 1980s and 1990s in yeast, and then in other eukaryotes. Remarkably, normal development requires that some healthy cells be eliminated, killed, by a process called "apoptosis." Initial clues about the nature of apoptosis came from detailed studies of the roundworm Caenorhabditis elegans, in which development of each of the 959 cells in the adult can be traced from the fertilized egg. Analysis of cell "fates" showed that specific cells are programmed to die at specific times during embryonic development. Disruptions in the program lead to an overabundance of cells a hallmark of cancer.

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Concept 39 A genome is an entire set of genes.

Each organism has a defining set of chromosomes that contain all of its genetic information. The human genome, for example, is the set of genetic information encoded in 46 chromosomes found in the nucleus of each cell. The chromosomes are organized into 23 pairs one chromosome of each pair is inherited from the mother and one from the father. One pair of chromosomes X and Y determine sex; the other 22 pairs are called autosomes. So, the human genome is made up of a set of very long DNA molecules, one corresponding to each chromosome. Arrayed along these molecules are an estimated 35,000 genes. The object of the Human Genome Project is to determine the entire nucleotide sequence of each of these DNA molecules and the location and identity of all the genes. Sequencing the human genome has relied mainly on automated machines that sequence the DNA and computer programs that search and identify genes. A "working draft" DNA sequence of the human genome was completed in June 2000. Initial analyses of this working draft were published in February 2001.

Concept 40 Living things share common genes.

All living organisms store genetic information using the same molecules DNA and RNA. Written in the genetic code of these molecules is compelling evidence of the shared ancestry of all living things. Evolution of higher life forms requires the development of new genes to support different body plans and types of nutrition. Even so, complex organisms retain many genes that govern core metabolic functions carried over from their primitive past. Genes are maintained over an organism's evolution, however, genes can also be exchanged or "stolen" from other organisms. Bacteria can exchange plasmids carrying antibiotic resistance genes through conjugation, and viruses can insert their genes into host cells. Some mammalian genes have also been adopted by viruses and later passed onto other mammalian hosts. Regardless of how an organism gets and retains a gene, regions essential for the correct function of the protein are always conserved. Some mutations can accumulate in non-essential regions; these mutations are an overall history of the evolutionary life of a gene.

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Concept 41 DNA is only the beginning for understanding the human genome.
Although DNA transmits genetic information through time, it basically has a passive role. Proteins encoded by DNA actually carry out the myriad cellular reactions that constitute "life." Now that the Human Genome Project has provided us with a catalog of tens of thousands of genes, we are left with the question: "What do proteins made by these genes actually do?" Scientists have always looked to mutant organisms to provide clues about protein function. Now, specific mutants can be created at will by inserting an altered or non-functioning copy of a gene back into a living organism, then looking for changes in behavior or development. Since mice breed quickly and share about 99% of their genes with humans, they have become the animal model of choice for large-scale functional studies. However, doing a single transgenic experiment is several orders of magnitude more difficult than sequencing the gene itself. The real work of understanding the human genome still lies ahead.

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Sumber: http://www.dnaftb.org/