Biology Textbook PDF - DNA, Genes, Proteins, Human Genome Project

Okay, here is the converted text from the images into a structured markdown format. ### BIOLOGY 4/5 FOR THE INTERNATIONAL STUDENT | 9780170353199 ## Making proteins Every cell in your body contains the same DNA, but the cells can look very different. For example, compare a cell in your eyeball wi...

Okay, here is the converted text from the images into a structured markdown format. ### BIOLOGY 4/5 FOR THE INTERNATIONAL STUDENT | 9780170353199 ## Making proteins Every cell in your body contains the same DNA, but the cells can look very different. For example, compare a cell in your eyeball with one in a muscle. The differences are due to the cells having different proteins, or different amounts of the same proteins. Proteins are classified as giant molecules, although protein molecules are not nearly as big as a human DNA molecule. Because of their size and complexity, protein molecules and DNA molecules are also termed biological macromolecules. Proteins perform many different functions in cells. Examples are: * 'gatekeepers' to the cell, embedded in cell membranes and controlling what comes in and out * 'messengers' between cells; for example, the hormone insulin is a protein that controls blood sugar levels * 'biological catalysts' called **enzymes**, which speed up reactions without being consumed in the process. Each of the thousands of reactions in our cells requires its own particular enzyme * 'structural proteins', which make up the 'building material' of our body, such as muscles, hair and fingernails * 'transport proteins', which include important molecules such as haemoglobin, the molecule that transports oxygen to our cells. Given the diverse range of protein functions, it is not difficult to understand why specialised cells in the same organism can appear so different. ### UNIT 5 | DNA - THE LIFE MOLECULE | 9780170353199 space in much the same way that walls divide a house. Throughout the cytoplasm there are smaller structures, called **organelles**. You probably know about two examples: **mitochondria**, which are responsible for making molecules that store energy for the cell; and **chloroplasts**, which are found in plant cells and are responsible for photosynthesis. As early as the 1880s, scientists hypothesised that mitochondria and chloroplasts may have originated from free-living bacteria that entered into a cell as **parasites** and gradually become **symbiotic**. Refined microscopy developed in the 1960s eventually supported the idea. By the 1980s, it was possible to extract and compare DNA from organelles and confirm its similarity to the DNA in groups of wild, free-living bacteria and cyanobacteria. This was the work of Lynn Margulis (Figure 5.12), a scientist whose ideas about the origin of eukaryotic cells steadily gained acceptance as a result of DNA analysis. **FIGURE 5.12** Professor Lynn Margulis (1938-2011) was a scientist whose radical ideas about the origin of eukaryotic cells became mainstream as a result of DNA analysis. **Image description:** A portrait photo of Professor Lynn Margulis. ### What DNA tells us about the origin of complex cells For a molecule that carries such a huge amount of information, DNA takes up amazingly little space. The nucleus makes up only 10% of the volume of **eukaryotic** cells (cells with 'true' nuclei) (Figure 5.11). Only 0.3% of the volume of the nucleus is DNA. The rest of the nucleus is water, and a collection of proteins. The cytoplasm around the nucleus is filled with almost invisible membranes, which greatly increase the surface area on which chemical reactions take place, and organise the ### Modelling DNA change over time Have you ever made two copies of a Word file, edited both, and then copied and edited each file again? You now have four files, in two 'generations'. If you forgot to label them, it may be difficult to work out what the original document said. This is particularly the case if you not only added information or words, but also deleted sections, phrases or sentences. It becomes more difficult if the document is very long, for example a book, and the changes you made were small, perhaps single words or even letters. Working out the sequence of changes is similar to the problem faced by scientists who study evolutionary relationships using DNA-DNA hybridisation, or the sophisticated statistical techniques that directly analyse DNA sequences, base by base. DNA mutations can include **insertions**, **deletions**, **repetitions**, **inversions** (flipping a section over so it is backwards) and **transpositions** (moving a section from one part of a strand to another). Some of these changes may have happened more than once, and have overlapped in the same region of the molecule. ### Human Genome Project The Human Genome Project revealed that only 5% of the entire genome holds useful genes, and there are only about 21 000 of them. The other 95% is sometimes called 'genetic junk'. More than 70% of this 'junk' consists of degraded viral genomes. It must have come from very ancient infections because we share it with the related primates the great apes. All this material has been copied, sometimes with benign errors, for tens of thousands of generations. ### The power of DNA #### DNA and relationships What makes DNA such a special molecule? The hydrogen bonds holding the two bases together provide the clue about how the molecule replicates itself. If you have a single strand of nucleotides, you can determine the order of nucleotides in the second strand. For example, a particular segment with base sequence AATGCCGGTAA will have a complementary sequence of TTACGGCCATT on the other strand. This arrangement provides a kind of insurance for the information the molecule carries. To change the sequence, an entire base pair would need to be inserted or deleted. Whenever a cell divides, the DNA molecule splits and each strand is copied. This results in two identical DNA molecules that will end up in one of the two daughter cells (Unit 6). Generally, each cell in an organism contains the same DNA, which ultimately controls the processes that occur in each cell. Differences between cells can generally be explained by cells using different parts of a DNA molecule, much like different users of a computer may use different software or files stored on its hard disk. DNA can also explain bigger differences within and between organisms. Changes called **mutations** can involve the replacement of nucleotides or sections of a DNA strand. In an individual, this type of change may result in differences in cells, for example, a cancer developing. Within a species, bigger differences that are common to groups can explain breeds (Figure 5.8, page 112). Differences between species can also be explained by comparing DNA (Figure 5.9, page 112). It may surprise you to learn that there is only a 1.6% difference between the DNA sequences of a ### Base pairs The base on each nucleotide is the key to the way DNA works. There are four different bases, so there are four possible nucleotides. These nucleotides are repeated over and over again along each strand, in all kinds of sequences. This is like making a giant necklace when you only have four kinds of beads to choose from. You can make many different arrangements, even with this restricted range of beads. The four bases present in a DNA molecule are guanine, cytosine, adenine and thymine, and they are usually represented as G, C, A and T. While they have many similarities, the structures of these four bases also have important differences. Due to their chemical structure, the bases can only form the 'rungs' of the ladder in two possible combinations. The only pairs that bond together are G with C, and A with T. These two combinations are known as **base pairs** (Figure 5.5). Notice the base pairs in Figures 5.5 and 5.6. The weak electrostatic forces that hold the base pairs together are called hydrogen bonds. These bonds occur between and within molecules, and consist of the attraction between a hydrogen atom and an electronegative atom such as oxygen or nitrogen. The bonds are easily disrupted if the DNA is exposed to acidic or basic solutions, or heat. In Figures 5.5 and 5.6, three dotted lines are shown between each C and G, but only two dotted lines between each A and T. This means A-T separates more easily than C-G, and is the basis for an important technique for comparing species. **Figure 5.5 The four bases at work** **Figure 5.6 DNA structure as a polymer** ### Explaining DNA #### Structure of DNA As you can see from Figure 5.3, DNA is a very long molecule that looks like a twisted ladder or spiral staircase. It consists of two chains (or strands) of atoms twisted around each other. This structure is called a double helix. The atoms within each strand are held together by covalent bonding, in which atoms form a strong connection by sharing electrons. The result is that the individual strands of the helix are difficult to break along their length. The two strands in the spiral are held together with hydrogen bonds, in which the atoms are attracted by electrostatic forces. This type of chemical bonding is much weaker, and is an important feature of DNA chemistry. The two strands of the helix need to be separated or 'unzipped' whenever the DNA molecule is copied and when it is used to instruct the cell how to make proteins. You will learn about this later in this unit. #### Repeating unit pattern DNA is a polymer, a giant molecule made of repeating units (monomers). Its monomers are called nucleotides. Therefore, DNA is a polynucleotide. Covalent bonds join one nucleotide to the next. As shown in Figure 5.4, each nucleotide is made up of three components: a base, a sugar and a phosphate group. Each strand of the DNA molecule consists of alternating sugar and phosphate groups. This is termed the sugar-phosphate backbone of DNA. The bases, which are attached to the sugar groups, hang off the backbone like the 'rungs' on a ladder. ### BIOLOGY 4/5 FOR THE INTERNATIONAL STUDENT | 9780170353199 As soon as two tRNAs have assembled side by side on the mRNA, the amino acids they carry join by reacting together. Then the first tRNA detaches from its mRNA codon. The whole assembly moves along the ribosome, ready for the next tRNA, and so on. The primary sequence of the protein grows as the amino acids gradually join one by one. This process is shown schematically in Figure 5.17 (page 119). #### Gene partnerships Not all proteins are coded for by one gene. Complex proteins often require two or more genes to work in partnership in order to build them. An example of this is haemoglobin (Figure 5.18), found in red blood cells. Haemoglobin molecules transport oxygen to body cells. These molecules are made up of two alpha-globin proteins and beta-globin proteins, each of which is a very long protein. They also contain iron ions, which give the red blood cells their colour. There are two genes that code for haemoglobin. One is the alpha-globin gene, which is about 1500 nucleotides long; the other is the beta-globin gene, and is about 1600 nucleotides long. With very few exceptions, the order of nucleotides that makes up these two genes is the same in every human. **Image description:** A haemoglobin molecule consisting of two alpha-globin proteins (red, orange) and two beta globin proteins (blue, purple). Four haem molecules are also visible. ### Translation: mRNA to protein The production of a peptide or a protein from mRNA is called **translation**. Each step in the process is assisted by one or more specialised proteins, or enzymes. The mature mRNA leaves the nucleus and enters the cytoplasm, where it binds with an organelle called a ribosome. The ribosome consists of two units that 'munch' along the mRNA strand like a clamp opening and closing along a rope. This process exposes sets of three bases on the mRNA, called **codons**. Codons are the templates for molecules of another type of RNA found in the cytoplasm, **transfer RNA (tRNA)**. There is at least one type of tRNA molecule for each of the 21 amino acids. In the cytoplasm, one end of a tRNA molecule temporarily connects to its free-floating amino acid and brings it to the ribosome. The other end of the tRNA has a set of three exposed bases, called an **anticodon**, which complements the exposed mRNA codon. This is how the right amino acid is matched to the right spot on the mRNA. **Image description:** A diagram illustrating translation. An mRNA molecule associates with a robosome. tRNA molecules bring amino acids to the ribosome, where a polypeptide chain is constructed. ### **Image Description:** A figure depicting the formation of mRNA. It shows how mRNA is produced from a DNA template through transcription. The production of mRNA from a DNA strand is called **transcription**. The DNA molecule unwinds and then 'unzips' in the region of the gene for the protein. This exposes the DNA bases along both strands, but only one of these, the **template strand**, is copied (Figure 5.16). The mRNA molecule is formed when free-floating RNA nucleotides in the nucleus pair up with the complementary DNA nucleotide on the template strand. Notice that in mRNA, the base uracil replaces thymine (Table 5.1) to pair up with adenine. Before mRNA leaves the nucleus and enters the cytoplasm, it is modified. A little 'cap' is added to the front of the chain and a 'tail' to the other end. Also, some bits (introns) are snipped out and the remainder (exons) spliced together. ### How genes make proteins Transcription: DNA to mRNA Crick and his team reasoned that if four bases are combined in triplets, this would give 64 ($4 \times 4 \times 4$) possibilities - not too many if some combinations are used more than once, and other sequences act as signals to start or stop 'reading' the information from the DNA template. This reasoning was eventually shown to be correct. A single-stranded polymer called **messenger RNA (mRNA)** acts as the go-between for the nucleus and cytoplasm. RNA is also a nucleic acid, but uses a different sugar, ribose, and a base called uracil instead of thymine. Table 5.1 summarises the differences between DNA and mRNA. **TABLE 5.1 A comparison of DNA and mRNA** | DNA | mRNA | | :----------------------------------------------------------------- | :-------------------------------------------------------------------- | | A nucleic acid | A nucleic acid | | Nucleotides form a very long double strand | Nucleotides form a much shorter single strand (about the size of a gene) | | Contains the sugar deoxyribose (hence the name deoxyribonucleic acid) | Contains the sugar ribose (hence the name ribonucleic acid) | | Contains the bases adenine (A), cytosine (C), guanine (G) and thymine (T) | Contains the bases adenine (A), cytosine (C), guanine (G) and uracil (U) | ### Switching genes on and off When cells specialise, many instructions in the DNA are not used. For example, our hair cells do not need to use instructions about building muscle or bone. But they do need instructions for making hair. So only necessary instructions are active, or switched on, and irrelevant instructions are made inactive, or switched off. Interestingly, if cells are transplanted so that they have to perform a new function, they can adapt and alter which instructions are active. ### Genes: linking the two living codes DNA and protein are two very different polymers. DNA is found in the nucleus and stores its information using a 'code' of hundreds of thousands of just four bases - A, T, G and C. Proteins are found mainly in the cytoplasm and stores its information using a 'code' of 20 amino acids. Immediately after the structure of the DNA molecule was understood, many scientists, including James Watson, began speculating how the sequence of bases might translate to the 20 amino acids known in proteins. Researchers began to look at how a particular section of DNA, consisting of a particular sequence and number of bases, might provide the information to instruct the primary sequence of amino acids. We now call these segments of DNA genes. Genes carry the information for making all the proteins required by all organisms. The principal role of DNA is to instruct cells to make specific proteins. Proteins determine the characteristics of the organism, including what it looks like, how well it fights infection and sometimes how it behaves. The entire collection of genes in an organism is called its genome. In the human genome, there are approximately 21000 genes and 3 billion pairs of bases altogether. **Figure 5.15 The different shapes of proteins determine their properties and functions** **Image description:** * **A fibrous protein, e.g. muscle, hair** A long strand of protein. * **A globular (ball-shaped) protein, e.g. an enzyme**. A squiggly sphere shape meant to depict an enzyme protein. Up to 20 different amino acids can be used to make proteins, although any one protein generally does not contain all of them. In humans, cells can manufacture some amino acids from other sources, but others, the 'essential amino acids', need to come directly from the diet. The sequence of amino acids in a protein is termed its primary structure (Figure 5.14). It is the primary structure that determines what happens next. Some amino acids are bulky, some repel water molecules, and some carry weak electrostatic charges. These intramolecular effects cause parts of the entire protein molecule to be pulled into a spiral shape, or a shape that resembles stairs, by weak hydrogen bonding between parts of the molecule. This bonding further pulls the protein into coils or even round 'balls' (Figure 5.15). The shape of the protein determines its properties and hence its function. **FIGURE 5.14 A schematic diagram of a section of a protein when it is stretched out (primary structure)** **Image description:** A string of connected circles. ### Protein structure Like DNA, proteins are polymers. The monomers of a protein are small molecules called **amino acids**, held together by strong covalent bonds. Unlike DNA, these only form a single strand. Proteins generally contain more than 100 amino acids (those with fewer amino acids are called peptides), but the total number varies for each protein. ### Recombinant DNA technology Recombinant DNA technology often relies on special proteins called restriction enzymes, isolated from bacteria, to recognise and cut specific short sequences of DNA. Another enzyme – DNA ligase (as in 'ligature') – joins sections of DNA together. Recombinant DNA technology is used to produce transgenic organisms, organisms that contain foreign genetic material, usually a useful gene selected from another completely unrelated species. Although many hundreds of transgenic organisms exist, it takes at least a decade for the original concept to be developed into a commercially useful product. Examples are listed in Table 5.2. No transgenic vertebrate animal has yet been approved for human consumption. **TABLE 5.2 Transgenic organisms** | Transgenic organism | Transformations caused by gene transfer | | :------------------------- | :------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | | Bt cotton | Bacillus thuringiensis is a bacterium that produces many types of proteins that are toxic to insects. Inserting the relevant genes into cotton means less insecticide needs to be sprayed, saving costs and reducing the impact on the environment. | | Golden rice | Genes for beta-carotene, which humans convert to vitamin A, have been transferred to a variety of rice popular in developing countries, where blindness as a result of vitamin A deficiency is common. | | Insulin-producing bacteria | Human insulin is now produced by transgenic bacteria grown in vats, which has eliminated allergic responses. | | Glofish | Originally developed to detect water pollution, these aquarium fish species are now part of the pet trade in some countries. Fluorescing proteins of different colours from corals and other marine species have been inserted into a variety of aquarium fish, including tetras, barbs and danios. | ### RNA interference RNA interference or RNAi is an emerging field of genetic modification that involves the use of injected, double-stranded RNA. In this technology, the mRNA is degraded when it binds to a complementary strand of RNA. The result is that the mRNA cannot be translated into a protein. It is a process that also seems to occur naturally in cells to regulate gene expression and to defend against attack by certain viruses. It is also used by a group of viruses, the double-stranded RNA viruses, to control the genomes of host cells. RNAi technology is extremely selective, as it will only target mRNA for enzymes that are involved in unwanted processes. Only tiny amounts of double-stranded RNA are needed to achieve an effect. The interference seems to spread to other cells and can be inherited. ### UNIT 5 | DNA - THE LIFE MOLECULE | 9780170353199 **TABLE 5.2 Transgenic organisms** | Transgenic organism | Transformations caused by gene transfer | | :------------------------- | :------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | | Bt cotton | Bacillus thuringiensis is a bacterium that produces many types of proteins that are toxic to insects. Inserting the relevant genes into cotton means less insecticide needs to be sprayed, saving costs and reducing the impact on the environment. | | Golden rice | Genes for beta-carotene, which humans convert to vitamin A, have been transferred to a variety of rice popular in developing countries, where blindness as a result of vitamin A deficiency is common. | | Insulin-producing bacteria | Human insulin is now produced by transgenic bacteria grown in vats, which has eliminated allergic responses. | | Glofish | Originally developed to detect water pollution, these aquarium fish species are now part of the pet trade in some countries. Fluorescing proteins of different colours from corals and other marine species have been inserted into a variety of aquarium fish, including tetras, barbs and danios. | ### BIOLOGY 4/5 FOR THE INTERNATIONAL STUDENT | 9780170353199 ### Huntington's disease Sometimes parts of the genome have repeat codons ('stutters'). In this genetic disease, a section of the genome coding for the amino acid glutamine ($CAG$) is repeated more than 35 extra times. The disorder causes premature senility when the brain cells fail in response to this different protein. The severity of the disease, and the age of onset, is closely related to the number of repeats. The number of repeats increases with each generation in families that carry the disease. ### Haemophilia Haemophilia is a group of hereditary genetic disorders that impair the control of blood clotting. Blood clotting requires a number of reactions, each controlled by a different protein, or 'factor'. One of these is factor VIII, a protein coded by a gene 186000 nucleotides long. Errors result in a faulty factor $VIII$ protein that contains more or fewer amino acids than normal. In people with haemophilia (Figure 5.20), bleeding is mostly internal, usually into the joints or muscles. These 'bleeds' can occur spontaneously or as the result of an injury, causing pain, swelling and tissue damage. **Image Description:** Figure 5.20 shows a person lying in a hospital bed, connected to some IV tubes. ### Genetic disorders Occasionally, errors (mutations) occur in the sequence of bases in a gene. These mutations can be harmful or beneficial, or have no effect. Genes that are very big tend to mutate more than others, and sometimes a tiny change can lead to disastrous consequences. A very positive outcome of the research undertaken for the Human Genome Project is that we can now screen for about 1500 genetic disorders. Obviously, we would all wish to avoid passing on faulty genes that can lead to serious health problems in our children. This is why many people with a particular family health history undertake genetic screening (testing the DNA of people for the presence of the particular genes that cause these conditions) and genetic counselling before starting a family. ### Cystic fibrosis One gene found in all humans is called the CFTR gene (cystic fibrosis transmembrane regulator gene). This gene codes for a very large protein (about 1500 amino acids long) that controls the salt balance on either side of the cells that line the lungs, the vas deferens (the tube along which sperm travel from the testes) and the pancreatic duct. The pancreas produces digestive enzymes as well as the hormone insulin. People who suffer from cystic fibrosis (Figure 5.19) get blockages in these parts of their body, have trouble breathing and digesting food, and experience infertility. Their life expectancy is usually only about 20-30 years unless they can have a heart-lung transplant. What has gone wrong? Cystic fibrosis sufferers have inherited a faulty CFTR gene. In about 70% of cases the gene only has one tiny mistake - three bases are missing out of the 4500 or so needed to code for the protein. This means a CFTR protein is made, but it has one less amino acid and doesn't work properly. **Image description:** A cystic fibriosis patient is undergoing physiotherapy.