What is Bioinformatics? Molecular Biology: Primer Raja Logananatharaj CACS, UL Lafayette There are many definitions. This is what I like: Design and development of computational models using data and domain knowledge or constraints from biologists to solve interesting problems in molecular biology What are the interesting Problems?? Before we review the basis of molecular biology, let us look into the central dogma of molecular biology. Cell Type There are two types of cell Prokaryotic cell does not have a nuclei Eukaryotic has a nuclei Differences between eukaryotic and prokaryotic gene expression In eukaryotes, one mrna = one protein. (in bacteria, one mrna can be polycistronic, or code for several proteins). DNA in eukaryotes forms a stable, compacted complex with histones. (in bacteria, the DNA is not in a permanently condensed state) Eukaryotic DNA contains large regions of repetitive DNA. (in bacteria, DNA rarely contains any "extra" DNA) Differences between eukaryotic and prokaryotic cont.. 4. Much of eukaryotic DNA does not code for proteins (~98% is non-coding in humans) (in bacteria, often more than 95% of the genome codes for proteins) 5. Sometimes, eukaryotes can use controlled gene rearrangement for increasing the number of specific genes. (in bacteria, this happens rarely) 6. Eukaryotic genes are split into exons and introns. (in bacteria, genes are almost never split) 7. In eukaryotes, mrna is synthesized in the nucleus and then processed and exported to the cytoplasm.(in bacteria, transcription and translation can take place simultaneously off the same piece of DNA) 1
The Central Dogma replication transcription translation DNA mrna protein Reverse transcription RNA virus can replicate themselves (RNA replication) and some can convert their RNA to DNA using reverse transcription. Example: HIV The Prokaryotic Dogma The Eukaryotic Dogma DNA polymerse RNA polymerse Ribosomes with rrna and trna transcription translation DNA mrna protein DNA polymerse RNA polymerse transcription splicing Ribosomes with rrna and trna translation DNA hnrna mrna protein nucleus cytosol 2
Transcription American scientists Craig Mello of the University of Massachusetts Medical School and Andrew Fire of Stanford University School of Medicine won The Nobel Prize in physiology or medicine on Monday for their discoveries related to RNA interference, a process that researchers hope to use to silence disease-causing genes. Transcription The process of converting the information contained in a gene into a protein. RNA polymerase binds to a certain sequence at the beginning of the gene, with the help from a factor called SIGMA, (Initiation). A small section of the DNA double helix unwinds exposing the bases on the two strands (Elongation). Another factor called RHO signals the synthesis to end (Termination). The result is a mrna molecule that carries the same information as the gene it was transcribed from. Splicing 3
Chromosome Structure Macromolecules Large molecules made up of chains of smaller molecules Also called biopolymers Macromolecules of special interest Deoxyribonucleic Acid (DNA) Ribonucleic Acid (RNA) Polypeptides (including proteins) 4
Deoxyribonucleic Acid (DNA) DNA is made from smaller molecules phosphoric acid (also called phosphate ) deoxyribose (a sugar) nitrogenous bases - four types: Adenine (A)( Thymine (T)( Cytosine (C)( Guanine (G)( Nucleotides Building Blocks of DNA Nitrogenous Bases Purines Pyrimidines 5
Nitrogenous Bases The bases are compounds known as Purines and Pyrimidines Purines have two rings Pyrimidines have one ring The rings make these very flat structures Purines: Adenine and Guanine Pyrimidines Thymine and Cytosine The small molecules form larger units Nucleosides deoxyribose plus a nitrogenous base Deoxyadenosine Deoxycytidine Deoxyguanosine Deoxythymidine 6
Nucleotides Phosphate + Sugar + Base Because there are 4 types of bases, there are 4 types of nucleotides Nucleotides are the basic unit of DNA and RNA structure Strings of nucleotides make up strands of DNA or RNA Nucleotide Phosphate + Deoxyribose + one of the four bases Bases are attached to the side of the sugar-phosphate backbone For each base, an N is bound to a C-1 in a deoxyribose Deoxythymidylic acid Here 3 nucleotides are joined to make one strand of DNA 7
DNA Double Helix monophosphate α 5 base: thymine (pyrimidine) sugar: 2 -deoxyribose A DNA double helix has two strands that run in opposite directions (antiparallel) The two strands in the double helix are held together by hydrogen bonds between the bases. (5 to 3 ) 4 3 3 linkage 1 2 5 linkage base:adenine (purine) no 2 -hydroxyl Hydrogen Bonds Hydrogen Bond 8
Nitrogenous Bases Highlighted 9
Base Pairing Rules Each of the four bases must be paired with a specific complementary base in the opposite strand A (Adenine) and T (Thymine) are complements C (Cytosine) and G (Guanine) are complements Adenine - Thymine Nucleotide Pair Two Strands of DNA are Held Together by Hydrogen Bonds between the bases Pairs of Nitrogenous Bases 10
Ribonucleic Acid Structure (RNA) Same overall structure In RNA ribose instead of deoxyribose uracil instead of thymine DNA is typically double stranded (but not always!) RNA is typically single stranded (but not always!) 11
Nucleotides Nucleotides 12
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