1. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 1. Enzymes build everything Enzymes allow nutrients to be digested; they convert food into energy and new raw materials; they build body structures; they govern all cellular processes. Thus, enzymes may be considered the quintessence of life. Enzymes allow nutrients to be digested; they convert food into energy and new raw materials; they build body structures; they govern all cellular processes. Thus, enzymes may be considered the quintessence of life. But, who builds the enzymes? But, who builds the enzymes?

2. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 2. The sequence of aminoacids The peptide bond. (a) A polypeptide is formed by the removal of water between amino acids to form peptide bonds. Each aa indicates an amino acid. R1, R2, and R3 represent R groups (side chains) that differentiate the amino acids. R can be anything from a hydrogen atom (as in glycine) to a complex ring (as in tryptophan). (b) The peptide group is a rigid planar unit with the R groups projecting out from the CN backbone. Standard bond distances (in angstroms) are shown.

3. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 3. Triplets of nucleotides How is amino acid sequence determined? Quite simply, by the nucleotide sequence present on a macromolecule of DNA. How is amino acid sequence determined? Quite simply, by the nucleotide sequence present on a macromolecule of DNA. The specific amino acid sequence of a polypeptide is determined by the nucleotide sequences of the gene that encodes it. The specific amino acid sequence of a polypeptide is determined by the nucleotide sequences of the gene that encodes it. The sequence of nucleotides in the DNA is read three nucleotides at a time. Each group of three, called a triplet codon, stands for a specific amino acid. The sequence of nucleotides in the DNA is read three nucleotides at a time. Each group of three, called a triplet codon, stands for a specific amino acid.

4. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 4. Decoding genes requires RNA The DNA in genomes does not direct protein synthesis itself, but instead uses RNA as an intermediary molecule. The DNA in genomes does not direct protein synthesis itself, but instead uses RNA as an intermediary molecule. When the cell needs a particular protein, the nucleotide sequence of the appropriate portion of the immensely long DNA molecule in a chromosome is first copied into RNA (a process called transcription). When the cell needs a particular protein, the nucleotide sequence of the appropriate portion of the immensely long DNA molecule in a chromosome is first copied into RNA (a process called transcription). It is these RNA copies of segments of the DNA that are used directly as templates to direct the synthesis of the protein (a process called translation). It is these RNA copies of segments of the DNA that are used directly as templates to direct the synthesis of the protein (a process called translation).

5. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 5. DNA  RNA  protein The flow of genetic information in cells is therefore from DNA to RNA to protein. The flow of genetic information in cells is therefore from DNA to RNA to protein.  All cells, from bacteria to humans, express their genetic information in this way—a principle so fundamental that it is termed the central dogma of molecular biology. The pathway from DNA to protein. The flow of genetic information from DNA to RNA (transcription) and from RNA to protein (translation) occurs in all living cells.

6. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 6. The flow of genetic information The expression of genetic information in all cells is very largely a one-way system: DNA specifies the synthesis of RNA and RNA specifies the synthesis of polypeptides, which subsequently form proteins. The expression of genetic information in all cells is very largely a one-way system: DNA specifies the synthesis of RNA and RNA specifies the synthesis of polypeptides, which subsequently form proteins. The first step, the synthesis of RNA using a DNA-dependent RNA polymerase occurs in the nucleus of eukaryotic cells and, to a limited extent, in mitochondria and chloroplasts, the only other organelles which have a genetic capacity in addition to the nucleus The first step, the synthesis of RNA using a DNA-dependent RNA polymerase occurs in the nucleus of eukaryotic cells and, to a limited extent, in mitochondria and chloroplasts, the only other organelles which have a genetic capacity in addition to the nucleus The second step, polypeptide synthesis, occurs in ribosomes, large RNA-protein complexes which are found in the cytoplasm and also in mitochondria and chloroplasts. The RNA molecules which specify polypeptide are known as messenger RNA (mRNA). The second step, polypeptide synthesis, occurs in ribosomes, large RNA-protein complexes which are found in the cytoplasm and also in mitochondria and chloroplasts. The RNA molecules which specify polypeptide are known as messenger RNA (mRNA). The expression of genetic information follows a colinearity principle: the linear sequence of nucleotides in DNA is decoded to give a linear sequence of nucleotides in RNA which can be decoded in turn in groups of three nucleotides (codons) to give a linear sequence of amino acids in the polypeptide product. The expression of genetic information follows a colinearity principle: the linear sequence of nucleotides in DNA is decoded to give a linear sequence of nucleotides in RNA which can be decoded in turn in groups of three nucleotides (codons) to give a linear sequence of amino acids in the polypeptide product.

7. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 7. The genetic code The table of correspondence between triplets and aminoacids is called the genetic code. The table of correspondence between triplets and aminoacids is called the genetic code. Since there are four different nucleotides in DNA (or in RNA), there are 4 × 4 × 4 = 64 different possible codons. This means that there are more condons than aminoacids. Since there are four different nucleotides in DNA (or in RNA), there are 4 × 4 × 4 = 64 different possible codons. This means that there are more condons than aminoacids. The same genetic code is used by virtually all organisms on the planet. There are some exceptions in which a few of the codons have different meanings. The same genetic code is used by virtually all organisms on the planet. There are some exceptions in which a few of the codons have different meanings. Thus, the information to arrange aminoacids in a specific sequence with a particular function is coded in a sequence of nucleotides in DNA. Thus, the information to arrange aminoacids in a specific sequence with a particular function is coded in a sequence of nucleotides in DNA. The process and the machinery that generates a protein from a DNA sequence is called the protein synthesis apparatus The process and the machinery that generates a protein from a DNA sequence is called the protein synthesis apparatus

8. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 8. Codons and aminoacids

9. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 9. Properties of the genetic code 1.The code is read in non overlapping groups of three nucleotides. Each group is called a codon. 2.There are no spaces or commas separating neighboring codons. This property is especially important in understand the effects of mutations on proteins. 3.The genetic code is redundant. There are 64 possible codons but only 20 amino acids. 4.There is a start codon corresponding to the amino acid methionine. When translation begins the first amino acid is always methionine. After translation this amino acid is removed as part of editing the protein. Note though that once translation has started, methionine can occur in the protein. 5.There are three non coding stop or nonsense codons. These tell the machinery of translation that the end of the protein has been reached. 6.Not all amino acids have an equal number of codons coding for it. For example, tryptophan has one codon while arginine has six codons 7.The code is almost universal. However, certain bacteria, mitochondria and protista have minor variations in their codes. The near universality of the code suggests that the code arose very early in the evolution of life.

10. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 10. The near universality of the decoding system Although DNA is the hereditary material in all present-day cells, it is most likely that early in evolution RNA served that function. RNA molecules can, like DNA, undergo self-replication. However, the 2′ hydroxyl group on the ribose residues of RNA makes the sugar- phosphate bonds comparatively unstable chemically. Although DNA is the hereditary material in all present-day cells, it is most likely that early in evolution RNA served that function. RNA molecules can, like DNA, undergo self-replication. However, the 2′ hydroxyl group on the ribose residues of RNA makes the sugar- phosphate bonds comparatively unstable chemically. Many different classes of present-day viruses nevertheless have a genome that consists of RNA, not DNA. Retroviruses such as HIV are a subclass of RNA viruses in which the RNA replicates via a DNA intermediate, using a reverse transcriptase, an RNA-dependent DNA polymerase. Many different classes of present-day viruses nevertheless have a genome that consists of RNA, not DNA. Retroviruses such as HIV are a subclass of RNA viruses in which the RNA replicates via a DNA intermediate, using a reverse transcriptase, an RNA-dependent DNA polymerase. Recently it has become clear that eukaryotic cells, including mammalian cells, contain nonviral chromosomal DNA sequences which encode cellular reverse transcriptases. Because some nonviral RNA sequences are known to act as templates for cellular DNA synthesis, the principle of unidirectional flow of genetic information is no longer strictly valid Recently it has become clear that eukaryotic cells, including mammalian cells, contain nonviral chromosomal DNA sequences which encode cellular reverse transcriptases. Because some nonviral RNA sequences are known to act as templates for cellular DNA synthesis, the principle of unidirectional flow of genetic information is no longer strictly valid

11. Genetica per Scienze Naturali a.a. 06-07 prof S. Presciuttini 11. Information flux in a living cell DNA Structural proteins Enzymes Metabolic pathways SugarsFatty acids Nucleotides Amino acids LipidsCarbohydrates