DNA: The Molecule of Heredity What enables cells to have so many different forms and perform so many different functions? Ultimately the source of this diversity is DNA. In simplest terms, DNA controls the production of proteins within the cell. These proteins in turn form the structural units of cells and control all chemical processes within the cell. Every new cell that develops in your body needs an exact copy of DNA from its parent cell. Likewise, humans and all other organisms must be able to pass copies of their DNA on to their offspring in order to continue the species. The structure of the DNA molecule is related to its two primary functions: 1. to store and use information to direct the activities of the cell 2. to copy itself exactly for new cells that are created Structure of DNA DNA and RNA are complex organic molecules. They are polymers; that is, they are composed of repeating subunits called monomers. The monomers of DNA and RNA are nucleotides. Nucleotides have three parts: 1. a five-carbon sugar molecule called deoxyribose 2. a phosphate group, composed of one atom of phosphorus surrounded by four oxygen atoms 3. a nitrogen base, which is a carbon ring structure that contains one or more atoms of nitrogen While the sugar molecule and phosphate group are the same in every nucleotide, the nitrogen base may be any one of 4 different kinds. 1. adenine (A) 3. thymine (T) 2. guanine (G) 4. cytosine (C) There are two families of nitrogenous bases: 1. Pyrimidines = a 6-membered (hexose) ring of carbon and nitrogen atoms - the members of the pyrimidine family are: a. cytosine (C) b. thymine (T) c. uracil (U) – in RNA 2. Purines = a 6-membered ring of carbon fused to a 5-membered (pentose) ring - the members of the purine family are: a. adenine (A) b. guanine (G) Nucleotides join together to form long chains, with the phosphate group of one nucleotide bonding to the deoxyribose sugar of an adjacent nucleotide, forming two strands bonded together and making up a molecule of DNA. The phosphate groups and deoxyribose molecules form the backbone of the chain, and the nitrogen bases stick out like teeth on a zipper. The 2 strands twist around a central axis to form a spiral structure called a double helix, first described by James Watson and Francis Crick. The two strands of DNA are held together by hydrogen bonds between the bases. Recall that a hydrogen bond is a type of chemical bond in which atoms share a hydrogen nucleus (i.e. one proton) In DNA, complementary hydrogen bonds form between purines and pyrimidines. More specifically, 1. adenine always bonds with thymine 2. cytosine always bonds with guanine = complementary base pairs What would the following chain pair with? (Pair up their complementary pairs below them) A–G–T–A–A–C–C–A–G–G–T–T–C This occurs because the structures complement each other in such a way that hydrogen bonds are established - adenine and thymine form only two hydrogen bonds - cytosine and guanine form three hydrogen bonds Therefore, the bases of one strand determine the bases on the other strand, that is, the two strands are said to be complementary strands The sequence of nucleotides forms the unique genetic information of an organism For example, a nucleotide sequence of A-T-T-G-A-C carries different info from a sequence of T-C-C-A-A-A In a similar way, two 6-letter words made of the same letters but arranged in different order have different meanings (e.g. formed and deform or crapes and scrape) The closer the relationship between two organisms, the greater the similarity in their order of DNA nucleotides Scientists now use nucleotide sequences to determine evolutionary relationships among organisms. Nucleotide sequences can also be used to determine whether two people are related, or whether the DNA from a crime scene matches the DNA of a suspected criminal Replication of DNA Before a cell can divide by mitosis or meiosis, it must first make a copy of its chromosomes. The DNA in the chromosomes is copied in a process called DNA replication Because DNA is composed of 2 strands that pair up complementary, you can predict the sequence of one strand from the other strand During replication, each strand serves as a pattern to make a new DNA molecule DNA replication begins as an enzyme breaks the hydrogen bonds between nitrogen bases that hold the two strands together, thus “unzipping” the DNA molecule. As the DNA continues to unzip, nucleotides that are floating free in the surrounding medium bond to the single strands by base pairing. Another enzyme bonds these new nucleotides into a chain This process continues until the entire molecule has been unzipped and replicated Each new strand formed is a complement of one of the original, or parent, strands. Thus, two identical DNA molecules are formed DNA Replication The copying of DNA is remarkable in its speed and accuracy. More than a dozen enzymes and other proteins participate in DNA replication. 1. Separation of Strands: When a cell begins to copy its DNA, the two nucleotide strands of a DNA molecule first separate at their base pairs when the hydrogen bonds connecting the base pairs are broken. As the DNA molecule unzips, the nucleotides are exposed. 2. Base Pairing: Free nucleotides base pair with exposed nucleotides. If one nucleotide on a strand has thymine as a base, the free nucleotide that pairs with it would be adenine. If the strand contains cytosine, a free guanine nucleotide will pair with it. Thus, each strand builds its complement by base pairing with free nucleotides. 3. Bonding of Bases: The sugar and phosphate parts of adjacent nucleotides bond together to form the backbone of the new strand. Each original strand is now bonded to a new strand. 4. Results of Replication: The process of replication produces two molecules of DNA. Each new molecule has one strand from the original molecule and one strand that has been newly synthesized from free nucleotides in the cell. RNA Like DNA, RNA is a nucleic acid. However, RNA structure differs from DNA structure in three ways: 1. An RNA molecule usually consists of a single strand of nucleotides, not a double strand. This single-stranded structure is closely related to its function. 2. The sugar in RNA is ribose, rather than the deoxyribose sugar of DNA. 3. RNA contains the nitrogen base uracil (U) in place of thymine (T). Uracil base pairs with adenine just as thymine does in DNA. RNA is involved in protein synthesis. It takes from DNA the instructions on how the protein should be assembled and it assembles it, amino acid by amino acid. There are 3 types of RNA that help to build proteins: 1. mRNA (messenger RNA) – brings info from the DNA in the nucleus to the cell’s cytoplasm. 2. rRNA (ribosomal RNA) – clamp onto the mRNA and use its info to assemble the amino acids in the correct order. 3. tRNA (transfer RNA) – transports amino acids to the ribosome to be assembled into a protein. How does the info in DNA, which is found in the nucleus, move to the ribosomes in the cytoplasm? mRNA carries this info from the DNA to the cell’s ribosomes. Transcription = The synthesis of RNA on a DNA template. In the nucleus, enzymes make an RNA copy of a portion of a DNA strand. This RNA copy is then moved to the cytoplasm via mRNA. The process of transcription is similar to that of DNA replication. The main difference is that transcription results in the formation of one single-stranded RNA molecule rather than a double-stranded DNA molecule. The Genetic Code The nucleotide sequence transcribed from DNA to a strand of mRNA acts as a genetic message, the complete info for the building of a protein. Recall that proteins are built from amino acid monomers. You could say, then, that the language of proteins uses an alphabet of amino acids. A code is needed to convert the language of mRNA into the language of proteins. There are 20 different amino acids, but mRNA contains only four types of bases. How can these bases form a code for proteins? Because they are sequenced in sets of 3. This means that the number of combinations for amino acids is 43 = 64. Codon = Each set of three nitrogen bases in mRNA coding for an amino acid. The order of nitrogen bases in the mRNA will determine the type and order of amino acids in a protein. Some codons do not code for amino acids; they provide instructions for assembling the protein. o o UAA & UAG & UGA = stop codon = indicates that protein production ends here AUG = start codon, as well as codon for the amino acid methionine More than one codon can code for the same amino acid. However, for any one codon, there can be only one amino acid. All organisms use the same genetic code for amino acids and assembling proteins. For this reason, the genetic code is said to be “universal”, and this provides evidence that all life on Earth evolved from a common origin. Translation (from mRNA to protein) = The synthesis of a polypeptide using the genetic info encoded in an mRNA molecule. There is a change of “language” from nucleotides to amino acids. How is the language of mRNA translated into the language of proteins? The process of converting the info in a sequence of nitrogen bases in mRNA into a sequence of amino acids that make a protein is known as translation. Translation takes place at the ribosomes in the cytoplasm. When the strands of mRNA arrive in the cytoplasm, the ribosomes attach to the like clothespins clamped to a clothesline. The Role of tRNA For proteins to be built, the 20 different amino acids dissolved in the cytoplasm must be brought to the ribosomes. This is the role of tRNA. Each tRNA molecule attaches to only one type of amino acid. Correct translation of the mRNA message depends upon the joining of each mRNA codon with the correct tRNA molecule. How does a tRNA molecule carrying its amino acid recognize which codon to attach to? On the opposite side of the tRNA molecule form the amino acid attachment site, there is a sequence of 3 nucleotides that are the complement of the nucleotides in the codon. These 3 nucleotides are called an anticodon because they bond to the codon of the mRNA. The tRNA carries only the amino acid that the anticodon specifies. Example = tRNA molecule for cysteine has the anticodon A – C – A This anticodon bonds with the mRNA codon U – G – U What is the mRNA codon for tryptophan? What is its tRNA anticodon? Translating the mRNA Code As translation begins, a tRNA molecule brings the first amino acid to the mRNA strand that is attached to the ribosome. The anticodon forms a temporary bond with the codon of the mRNA strand. Usually, the first codon on mRNA is AUG, which codes for the amino acid methionine. AUG signals the start of protein synthesis. The ribosome slides down the mRNA chain to the next codon, and a new tRNA molecule brings another amino acid. When the first and second amino acids are in place, an enzyme joins them by forming a peptide bond between them. After amino acids are bonded, the tRNA will release its amino acid and it detaches from the mRNA. The tRNA is now free to pick up another specific amino acid molecule and bring it to the ribosome. This process continues until a chain of amino acids is formed and the ribosome reaches a stop codon (UAA, UAG, or UGA) on the mRNA strand. Amino acid chains become proteins when they are freed from the ribosome and twist and curl into specific, complex, 3-D shapes. These proteins become enzymes and cell and tissue structures. The formation of protein, originating from the DNA code, produces the diverse and magnificent living world. Mutations = changes in the genetic material of a cell 1. Nondisjuction (already discussed) 2. Mutagens (already discussed) 3. Point Mutations = Changes in just one (or a few) base pairs in DNA (or a single gene) a. Base-Pair Substitutions = The replacement of one nucleotide (and its partner in the complementary DNA strand) with another pair of nucleotides. i. Silent Mutations = Substitutions that have no effect on the encoded protein due to the redundancy of the genetic code. - example: CCG mutated to CCA, the mRNA codon that used to be GGC would become GGU, and a glycine would still be inserted ii. Missense Mutations = The altered codon still codes for an amino acid and thus makes sense, although not not necessarily the “right” sense iii. Nonsense Mutations = Alterations that change an amino acid codon to a stop signal (codon) - nearly all nonsense mutations lead to nonfunctional proteins b. Base-Pair Insertions = The addition of one or more nucleotide pairs in a gene, or in the DNA c. Base-Pair Deletions = The deletion of one or more nucleotide pairs in a gene, or in the DNA 4. Frameshift Mutations = A mutation in which the number of nucleotide bases added or deleted from DNA is not a multiple of 3 (codon #) = alteration of the “reading frame” of the genetic message - All of the nucleotides downstream from the insertion or deletion will be improperly grouped into codons, and the result will be extensive missense ending sooner or later in nonsense In general, a point mutation is less harmful than a frameshift mutation, to an organism, because it disrupts only a single codon. Summaries: DNA vs. RNA DNA storage of Function genetic info 2 # of Strands deoxyribose 5-C Sugar Nitrogenous Bases A, T, C, G RNA transmission of genetic info 1 ribose A, U, C, G Base-Pairing Rules: DNA DNA (as seen in replication) DNA RNA (as seen in transcription) G – C and C – G T – A and A – T G – C and C – G T – A and A – U The Triplet Code One set of 3 consecutive nucleotides (bases) represents and amino acid 3 bases in: DNA “code” mRNA “codon” tRNA “anticodon” From Gene to Protein 1. Transcription (DNA mRNA) - basic steps: a. DNA strands are separated b. complementary RNA nucleotides pair with one side of the DNA molecule c. RNA nucleotides are joined (backbone is “sealed”) d. mRNA molecule exits the nucleus while DNA strands rejoin 2. Translation (mRNA polypeptide) - basic steps: a. initiation = ribosome attaches to mRNA strand at the start codon b. elongation = tRNA’s deposit amino acids in the proper order - peptide bonds link the amino acids together c. termination = ribosome reaches a stop codon - ribosome detaches from mRNA - completed protein is released Ribosome movement and codon-anticodon base pairing ensure amino acids are arranged in the proper sequence Alterations During Replications 1. Point Mutations a. Substitutions (silent, missense, nonsense) b. Insertions c. Deletions 2. Frameshift Mutations NUCLEOTIDE The mRNA Genetic Code