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BINF 730
Biological Sequence Analysis
Saleet Jafri Program in Bioinformatics and Computational Biology
George Mason University
Lecture 1
Overview of Molecular and Cellular Biology
Biological References
- Molecular Biology of the Cell by Bruce Alberts (1994 or newer edition)
- Molecular Cell Biology by Darnell, Lodish , and Baltimore (1995 or newer edition)
Part I: Molecular Biology Review
Where do biological sequences come from?
- Life and evolution
- Proteins
- Nucleic Acids
- Central dogma
- Genetic code
- DNA structure
- Mitochondrial DNA
Life
- Evolved from common origin
- ˜3.5 billion years ago
- All life shares similar biochemistry
- Proteins: active elements
- Nucleic acids: informational elements
- Molecular Biology: the study of structure and function of proteins and nucleic acids
Terrestrial Life
Cell types
Prokaryotes – no nuclear membrane, represented by cyanobacteria (blue-green algae) and common bacteria ( Escherichia coli )
Eukaryotes – unicellular organisms such as yeast and multicellular organisms
Archaebacteria – no nuclear membrane but similar to eukaryotes in transcription and translation mechanisms, discovered in deep sea thermal vents in 1982
Prokaryotic Cell
Prokaryotic Cell Eukaryotes
- In eukaryotes, transcription is complex:
- Many genes contain alternating exons and introns
- Introns are spliced out of mRNA
- mRNA then leaves the nucleus to be translated by ribosomes
- Genomic DNA: entire gene including exons and introns
- The same genomic DNA can produce different proteins by alternative splicing of exons
- Complementary DNA ( cDNA): spliced sequence containing only exons - cDNA can be manufactured by capturing mRNA and performing reverse transcription
Eukaryotic Cell
Eukaryotic Cell
RNA
- Different sugar (ribose instead of 2’-deoxyribose)
- Uracil (U) instead of thymine (U binds with A)
- RNA does not form a double helix
- RNA may have a complex three-dimensional structure
Central Dogma
DNA? RNA? Protein
DNA = Deoxyribonucleic Acid
RNA = Ribonucleic Acid
Protein = Functional and Structural units of cells
Flow of Information is unidirectional
Gene Transcription or DNA
Transcription
- RNA molecules synthesized by RNA polymerase
- RNA polymerase found in free and bound form
- RNA polymerase binds very tightly to promoter region on DNA
- Promoter region contains start site
- Transcription ends at termination signal site.
- Primary transcript – direct coding of RNA from DNA
- RNA splicing – introns removed to make the mRNA
- mRNA – contains the sequence of codons that code for a protein
- uracil replaces thymine
- splicing and alternative splicing
Translation
- Ribosomes made of protein and ribosomal RNA ( rRNA)
- Transfer RNA ( tRNA) make connection between specific codonsin mRNA and amino acids - As tRNAbinds to the next codon in mRNA, its amino acid is bound to the last amino acid in the protein chain
- When a STOP codon is encountered, the ribosome releases the mRNA and synthesis ends
Gene Translation
- tRNA – links an amino acid to the codon on the mRNA via the anit -codon
- rRNA – RNA found in ribosomes
- ribosomes – large and small subunit, made of protein and rRNA
- initiator tRNA always carries methionine
- initiation factors – proteins that catayze the start of transcription
- stop codon
- Endoplasmic Reticulum
- Posttranscriptional modification
Translation
- Involves ribosomes , and RNA
- Ribosomes made of protein and RNA
- Messenger RNA (mRNA) is the sequence transcribed from the DNA
- The mRNA is ‘threaded’ through the ribosomes.
- Transfer RNA ( tRNA) brings the different amino acids to the ribosome complex so that the amino acids can be attached to the growing amino acid chain.
Ribosome
Protein – amino acid chain
tRNA
Amino acid
mRNA
Ribosome Ribosomal RNA
Eukaryotic and Prokaryotic
Ribosome Structure
LSU
LSU
SSU
SSU
Gene Coding and Replication
- Double helix
- Nitrogenous bases A,T,G,C
- Sugar-Phosphate backbone
- Nucleotide – sugar + base + phosphate group
- Nucleoside – sugar + base
- Purines – adenine, guanine
- Pyrimidines – cysteine, thymine
- A-T – 2 H bonds, G-C – 3 H bonds
Gene Coding and Replication
- 5’ end contains a phosphate group
- 3’ end is free
- DNA extended from 5’ to 3’
- Gene is a segment of DNA that codes for a specific protein
- Exons are coding regions of the DNA
- Introns are ‘in between ’ regions, found in eukaryotes
- Codons
- Reading frame
- Consensus sequences are conserved regions found in a particular type of regulatory region
Mitosis
QuickTime™ and a Sorenson Video decompressor are needed to see this picture.
Proteins
- Functions:
- Structural proteins
- Enzymes
- Transport
- Antibody defense
- Chains of amino acids
- Typical size ~300 residues
Protein Folding
- Primary structure – amino acid sequence
- Secondary structure – local structure such as? helix and? sheets
- Tertiary structure – 3-dimensional structure of a protein monomer
- Quarternary structure – 3-dimensional structure of a fully functional protein (protein complexes).
Primary structure: residue sequence
Secondary structure: local structures (Helices, sheets, loops)
Tertiary structure: position of each atom
Quaternary structure:
how groups of proteins pack together
The protein’s 3-d shape determines what molecules it can bind to
Unsolved problem: predicting a protein’s folding pattern based on its sequence
Cell Signaling and Biochemical
Pathways
- Surface receptors
- G-proteins, kinases , etc
- Transcription factors
- Other biochemical reactions – glycolysis , citric acid cycle, etc.
Molecular Biology Summary
- Life and evolution
- Proteins
- Nucleic Acids
- Eukaryotes versus Prokaryotes
- Ribosome
- Translation
- Transcription
- Central dogma
- Genetic code
- DNA structure
- Chromosome
- Mitosis
