Basic concepts of molecular biology

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1 Basic concepts of molecular biology Gabriella Trucco

2 What is life made of? 1665: Robert Hooke discovered that organisms are composed of individual compartments called cells Great diversity of cells in nature, but they all have some common features All cells have a life cycle: they are born, eat, replicate, and die Many important decisions, but cells do not have brains complex networks of chemical reactions: pathways More detailed discussions can be found in introductory biology textbooks like T. Brown. Genomes. JohnWiley and Sons, New York, B. Lewin. Genes VII. Oxford University Press, Oxford, UK, B. Alberts, D. Bray, J. Lewis, M. Raff, K. Roberts, and J. Watson. Molecular Biology of the Cell. Garland Publishing, New York, 1994.

3 The cell structure

4 What is life made of? All life on this planet depends on two types of molecule: Proteins: many different kinds: Structural proteins, enzymes, nucleic acids: two kinds of nucleic acids: ribonucleic acid, abbreviated by RNA, and deoxyribonucleic acid, or DNA

5 What is life made of? cell s DNA :library describing how the cell works RNA acts to transfer certain short pieces of information to different places in the cell Proteins form enzymes that perform biochemical reactions, send signals to other cells, form the body s major components (like the keratin in our skin), and otherwise perform the actual work of the cell. DNA, RNA, and proteins are examples of strings written in either the four letter alphabet of DNA and RNA or the twenty-letter alphabet of proteins.

6 Proteins chain of simpler molecules called amino acids Aminoacid one central carbon atom hydrogen atom amino group (NH2) carboxy group (COOH) side chain

7 Proteins There are 20 common amino acids (aa s); two systems of abbreviations are used: 3-letter-code and 1-letter-code. We usually use the 1-letter-code. alanine Ala A arginine Arg R asparagine Asn N aspartic acid Asp D cysteine Cys C glutamine Gln Q glutamic acid Glu E glycine Gly G histidine His H isoleucine Ile I leucine Leu L lysine Lys K methionine Met M phenylalanine Phe F proline Pro P serine Ser S threonine Thr T tryptophan Trp W tyrosine Tyr Y valine Val V

8 Proteins Peptide bonds Backbone Primary, secondary, tertiary, and quaternary structures of proteins

9 DNA Discovered in 1869 Basic unit (nucleotide): - sugar - phosphate group - nitrogenous base 4 bases (nucleotides): - Adenine (A) - Cytosine (C) - Guanine (G) - Thymine (T)

10 Structure of DNA

11 DNA: nucleotides 5...AACAGTACCATGCTAGGTCAATCGA TTGTCATGGTACGATCCAGTTAGCT...5 orientation (read from 5 to 3 end) length measured in bp (base pairs) double stranded, the two strands are antiparallel A - T and C - G complementary (Watson-Crick pairs) DNA as string of letters, each letter representing a base. "string-view" of DNA: one of the strings on top of the other

12 Connection between DNA and proteins Proteins could not be made directly from DNA DNA resides within the nucleus, whereas protein synthesis had been observed to happen outside the nucleus, in the cytoplasm mid 1950s: Paul Zamecnik discovered that protein synthesis in the cytoplasm happens with the help of certain large molecules called ribosomes that contain RNA. DNA as a template used to copy a particular gene into messenger RNA (mrna) that carries the gene s genetic information to the ribosome to make a particular protein. RNA: 4 characters A C U G: adenine, cytosine, uracil, guanine (U instead of T)

13 Genes Certain contiguous stretches along DNA encode information for building proteins, but others do not This stretch is known as a gene Protein: chain of amino acids Triplets of nucleotides specify each amino acid Each nucleotide triplet is called a codon Genetic code: table that gives the correspondence between each possible triplet and each amino acid

14 The genetic code Degeneracy of the genetic code: 64 codons but only 20 aa s plus stop codon Silent mutations: if third position mutates, this often does not alter the aa

15 The central dogma of molecular biology How the information in the DNA results in proteins Promoter AUG Transcription: copy of the gene made on an RNA molecule (messenger RNA, or mrna ). This resulting RNA will have exactly the same sequence as one of the strands of the gene but substituting U for T The strand identical to the mrna is called coding strand The other strand (the one which is used for the transcription) is called template strand

The central dogma of molecular biology Translation: trna make the connection between a codon and the specific amino acid this codon codes for Each trna molecule has, on one side, a conformation that

16 The central dogma of molecular biology Translation: trna make the connection between a codon and the specific amino acid this codon codes for Each trna molecule has, on one side, a conformation that has high affinity for a specific codon and, on the other side, a conformation that binds easily to the corresponding aa As the messenger RNA passes through the ribosome, a trna matching the current codon binds to it, bringing the corresponding amino acid When a STOP codon appears, no trna associates with it, and the synthesis ends

17 Example The transcription of DNA into RNA, and the translation of RNA into a protein

18 Strings in molecular biology Many other problems in molecular biology can be modelled by strings (e.g. gene order, haplotypes,... ) Strings are finite sequences over an alphabet S (also called sequences) DNA (characters: nucleotides) S = {A,C,G,T} RNA (characters: nucleotides) S = {A,C,G,U} Proteins (characters: peptides) S = {A,C,D,E,F,...,W,Y}

19 Reading frames Reading frame: one of the three possible ways of grouping bases to form codons in a DNA or RNA sequence 3 different reading frames for translation: The DNA sequence 5...TATTCGAATCGGC...3 can be translated in 3 different ways, leading to different aa sequences

Basic concepts of molecular biology

Basic concepts of molecular biology Gabriella Trucco Email: gabriella.trucco@unimi.it Life The main actors in the chemistry of life are molecules called proteins nucleic acids Proteins: many different