INTRODUCTION TO MOLECULAR BIOLOGY SALWA HASSAN TEAMA M

INTRODUCTION TO MOLECULAR BIOLOGY SALWA HASSAN TEAMA M. D.

THE GENOME DATABASE The genome database is organized in six major organism groups: § Eukaryotes § Bacteria § Archaea § Viruses § Viroids § Plasmids

EUKARYOTIC CELLS PROKARYOTIC CELL

EUKARYOTIC CELL § Eukaryotic cells are found in animals, plants, fungi and protists § § § § cell Cell with a true nucleus, where the genetic material is surrounded by a membrane Eukaryotic genome is more complex than that of prokaryotes and distributed among multiple chromosomes Eukaryotic DNA is linear Eukaryotic DNA is complexed with proteins called histones Numerous membrane-bound organelles Complex internal structure Cell division by mitosis

PROKARYOTIC CELL § Unicellular organisms, found in all environments. These § § § include bacteria and archaea Without a nucleus; no nuclear membrane (genetic material dispersed throughout cytoplasm No membrane-bound organelles Cell contains only one circular DNA molecule contained in the cytoplasm No histone protein Simple internal structure Cell division by simple binary fission

ARCHAEA Archaea is prokaryotes; but some aspects of their molecular biology are more similar to those of eukaryotes. Source: Wikipedia

THE GENOME § The genetic information of an organism. § Encoded in the DNA (for some viruses, RNA). 7

THE GENOME SIZE

HUMAN CHROMOSOME Human Genome; arranged on multiple chromosomes; twenty three pairs of chromosomes; § Twenty two pairs (autosomes). § One pair (sex chromosome) (xx) (female) or (xy) (male). Humans have 23 pairs of chromosome in every cell (except mature red blood cells. ); Gametes or sex cells (sperm and eggs) have half the normal complement of chromosomes.

GENERAL STRUCTURE OF NUCLEIC ACID DNA and RNA are long chain polymers of small chemical compound called nucleotides.

Nucleotides § Nitrogenous base; these bases are classified based on their chemical structures into two groups: § Purine; double ringed structure (Adenine and Guanine). § Pyrimidine; single ring structures (cytosine thymine and uracil). § Sugar § Phosphate group

THE DEOXYRIBONUCLEIC ACID Deoxyribonucleic Acid (DNA); the genetic material of all cellular organisms and most viruses. DNA; the gigantic molecule which is used to encode genetic information for all life on Earth.

DNA DOUBLE HELIX q q Linked as a twisted ladder. The curving sides of the ladder represent the sugar-phosphate backbone of the two DNA strands; the rungs are the base pairs. Possess antiparallel polarity. Stabilized by hydrogen bonds between the bases.

THE GENE The gene; it is a segment within a very long strand of DNA. Genes are the basic units of hereditary. Genes located on chromosome on its place or locus. Allele; a variant of the DNA sequence at a given locus.

THE GENE Source: National Human Genome Research Institute.

GENE STRUCTURE § Eukaryotic gene structure: § The average gene 7 -10 exons spread over 1016 kb of DNA. § The gene must have (Exon; start signals; stop signals; regulatory control elements). §Gene structure §Exons (The coding sequences) § Introns (The non coding sequences). 16

GENE STRUCTURE The genes consist of; short coding sequences or exons are interrupted by a longer intervening noncoding sequence or introns; although a few genes in the human genome have no introns.

THE RIBONUCLEIC ACID § Three major classes of RNA: messenger (m. RNA), transfer (t. RNA) and ribosomal (r. RNA). § RNA is a single stranded; the pyrimidine base uracil (U) replaces thymine and ribose sugar replaces deoxyribose.

MESSENGER RNA/ m. RNA § Transcripts of structural genes. § Encode all the information necessary for the synthesis of a polypeptide of protein. § The 5' terminus is capped by 7 methyguanosine triphosphate. § Synthesis of the poly (A) tail involves cleavage of its 3' end and then the addition of about 200 adenine residues. § Intermediate carrier of genetic information; deliver genetic information to the cytoplasm. 19

TRANSFER RNA/ t. RNA §The t. RNAs has a common secondary structure resembles a cloverleaf: They have four basepaired stems defining three stem-loops (the D loop, anticodon loop, and T loop) and the acceptor stem. § t. RNA carry correct amino acids to their position along the m. RNA template to be added to the growing polypeptide chain. 20

TRANSFER RNA/ t. RNA 21

RIBOSOMAL RNA/ r. RNA § The central component of the ribosome. § Ribosome; factory for protein synthesis; composed of ribosomal RNA and ribosomal proteins (known as a Ribonucleoproteinor RNP). § r. RNA provides a mechanism for decoding m. RNA into amino acids.

DNA molecules serve as templates for either complementary DNA strands during the process of replication or complementary RNA during the process of transcription. RNA molecules serve as a template for ordering amino acids by ribosomes during protein synthesis.

GENE EXPRESSION Gene expression which a gene's information is converted into the structures and functions of a cell. Gene expression; the process of producing a biologically functional molecule of either protein or RNA (gene product) is made. Gene expression is assumed to be controlled at various points in the sequence leading to protein synthesis. 24

GENE EXPRESSION Transcription RNA polymerase makes a copy of information in the gene (complementary RNA) complementary to one strands of DNA. Translation Occurs on ribosomes, messenger RNA decoded or translated to determine the sequence of amino acid in the protein being synthesized.

GENE EXPRESSION §Transcription §RNA processing §Translation §Post-translation processing

TRANSCRIPTION 27

RNA Processing (Pre-m. RNA → m. RNA) Capping The cap structure is added to the 5' of the newly transcribed m. RNA precursor in the nucleus prior to processing and subsequent transport of the m. RNA molecule to the cytoplasm. Splicing Joining of exons; it takes place on a special structure called spliceosomes. Addition of poly A tail Synthesis of the poly (A) tail involves cleavage of its 3' end and then the addition of about 40 - 200 adenine residues to form a poly (A) tail. 28

ALTERNATIVE SPLICING § Alternative splicing: is a very common phenomenon in higher eukaryotes. It is a way to get more than one protein product out of the same gene and a way to control gene expression in cells. 29

THE GENETIC CODE q The sequence of codons in the m. RNA defines the primary structure of the protein. q Three nucleotides in m. RNA (codon) specify one amino acid in a protein. 30

THE GENETIC CODE 31

PROTEIN STRUCTURE 32

HUMAN GENOME PROJECT HGP is an international project aiming for: q Sequencing and localization of the base sequence that makes up human DNA. q Store this information in databases. q Mapping of human genome

Functional Genomics / Transcriptomics/ Proteomics Genomics: Involves the sequencing the genome, including structural gene, regulatory sequences and noncoding DNA segments in the chromosome of an organism and the interpretation of the structural and functional implications of these sequences and of many transcripts and proteins the genome encode. Transcriptomics: is the systematic and quantitative analysis of the transcript (the transcriptome) present in a cell or a tissue. Proteomics: It is the quantitative study of the proteome; the proteins expressed from the genome of cell via transcriptome. 34

Source: European Bioinformatics Institute

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