overview of molecular biology
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Overview of Molecular Biology. Each species has a uniquely fundamental set of genetic information, its genome . The genome is composed of one or more DNA ( d eoxyribo n ucleic a cid) molecules (46 in human beings), each organized as a chromosome . - PowerPoint PPT PresentationTRANSCRIPT
Overview of Overview of Molecular BiologyMolecular Biology
Each species has a uniquely fundamental set of genetic information, its genome.
The genome is composed of one or more DNA (deoxyribonucleic acid) molecules (46 in human beings), each organized as a chromosome.
Prokaryotic genomes are mostly single circular chromosomes.
Eukaryotic genomes consist of usually two sets of linear chromosomes confined to the nucleus.
A gene is a segment of DNA that is transcribed into a RNA molecule used to make proteins.
Introns interrupt many eukaryotic genes. Viral genomes consist of either DNA or RNA.
The Cell: Storehouse of The Cell: Storehouse of Hereditary/Genetic InformationHereditary/Genetic Information
The Cell Origin of life on Earth about 3.5 billion years ago Organisms are made up of cells, which can be decomposed into
organelles, then into molecules. The Cell Theory:
all living things are composed of one or more cells cells are basic units of structure and function in an organism cells come only from the reproduction of existing cells
Two basic classes of cells prokaryotic (pro = before, karyon = nucleus) cell: simpler, represented
by bacteria and blue algae eukaryotic (eu = true, karyon = nucleus) cell: structurally more
complex, all other organism types, such as protists, fungi, plants and animals
Both prokaryotic and eukaryotic cells share a similar molecular chemistry. Most important molecules are proteins and nucleic acids.
Protein StructureProtein Structure
• Proteins are polypeptides of 70-3,000 amino acids.• This structure is (mostly) determined by the sequence of amino acids that make up the protein.• There are 20 amino acids commonly found in proteins
Amino Acid Amino Acid FamiliesFamilies
DNA is a nucleic acid, made of long chains of nucleotides
DNA and RNA are polymers of nucleotides
Nucleotide
Phosphate group
Nitrogenous base
Sugar
Polynucleotide Sugar-phosphate backbone
DNA nucleotide
Phosphategroup
Nitrogenous base(A, G, C, or T)
Thymine (T)
Sugar(deoxyribose)
DNA has four kinds of bases: A, T, C, and G DNA has four kinds of
bases:
A, T, C, and G
Pyrimidines
Thymine (T) Cytosine (C)
Purines
Adenine (A) Guanine (G)
DNA molecules consist of double helix strands, which are antiparallel complementary base pairing rules: adenine (A) only pairs with thymine
(T), and guanine (G) only pairs with cytosine (C) the pairs of bases form base pairs (bp) reverse complementation of s = AGCTAAC in the 5’ 3’ direction is
= GTTAGCTs
Three Representations of DNA
Figure 10.3D
Ribbon model Partial chemical structure Computer model
Hydrogen bond
The Human GenomeThe Human Genome
• 22 pairs of chromosomes called autosomes• Two sex chromosomes (X,Y): XY in males and XX in females
Relative Size of GenomesRelative Size of Genomes
Genes: The Functional Part Genes: The Functional Part of DNAof DNA
A gene is certain region of DNA which is converted during a process called transcription into an intermediate sequence of chemically distinct nucleotides called an RNA (different types such as mRNA, tRNA, etc.) In a process called translation, RNA is then used to produce proteins that can be used by the cell to maintain its activity. The entire process is sometimes called the “central dogma” of molecular biology.
Structure of GenesStructure of Genes
Introns and Exons in GenesIntrons and Exons in Genes
•Exons: coding regions of genes•Introns: noncoding regions (“junk” DNA)
RNA is also a nucleic acid RNA has a slightly different sugar: ribose rather than deoxyribose RNA has U instead of T to bind with A RNA does not form a double helix; three-dimensional structure of
RNA is far more varied than that of DNA
Figure 10.2C, D
Phosphategroup
Nitrogenous base(A, G, C, or U)
Uracil (U)
Sugar(ribose)
Questions About ProteinsQuestions About Proteins
Given a strings of amino acids, determine if similar sequences are in the database.
Given a strings of amino acids, predict secondary structure.
Given a strings of amino acids, predict interactions with other macromolecules, i.e. identify sequence motifs.
Given a strings of amino acids, predict function.
Questions About DNAQuestions About DNA Given a string of nucleotides, determine if there are similar
sequences in the database.
Given a string of nucleotides, determine if it is informational: (1) find exons, (2) find splice junctions, (3) find promoters, (4) find regulatory sequences, and (5) evaluate for taxa-specific codon bias (different organisms often show particular preferences for one of the several codons that encode the same given amino acid; how these preferences arise is a much debated area of molecular evolution).
Given a string of nucleotides, find RNA secondary structure.
Given a string of nucleotides, find repeated sequences.
The “Central Dogma” of The “Central Dogma” of Molecular BiologyMolecular Biology
•Replication: DNA copies itself into two identical strings although copying errors may occur called mutations.
•Transcription: A gene is converted into an intermediate sequence of chemically distinct nucleotides called an RNA (different types such as mRNA, tRNA, rRNA, etc.).
•Translation: RNA is further decoded to produce the functional activity of a gene which usually takes the form of a protein.
Central Dogma of Molecular Biology (in flowchart form)
The “Central Dogma” in The “Central Dogma” in Prokaryotes and EukaryotesProkaryotes and Eukaryotes
Transcription BasicsTranscription Basics•RNA molecule is synthesized from a segment of DNA that includes a gene
•RNA nucleotides are similar to DNA nucleotides but have a (slightly) different backbone. In particular, DNA and RNA are composed of repeating units of nucleotides. Each nucleotide consists of a sugar, a phosphate and a nucleic (nitrogenous) acid base. The sugar in DNA is deoxyribose. The sugar in RNA is ribose, the same as deoxyribose but with one more OH (oxygen-hydrogen atom combination called a hydroxyl).
•T is replaced with U (U = Uracil)
GATTACA GAUUACA
In transcription, the DNA helix unzips
RNA nucleotides line up along one strand of the DNA following the base-pairing rules
The single-stranded messenger RNA peels away and the DNA strands rejoin
RNA polymerase
DNA of gene
PromoterDNA Terminator
DNAInitiation
Elongation
Termination
Area shownin Figure 10.9A
GrowingRNA
RNApolymerase
Completed RNA
Noncoding segments called introns are spliced out
A cap and a tail are added to the ends
Eukaryotic RNA is processed before leaving the nucleus
DNA
RNAtranscriptwith capand tail
mRNA
Exon Intron IntronExon Exon
TranscriptionAddition of cap and tail
Introns removed
Exons spliced together
Coding sequence
NUCLEUS
CYTOPLASM
Tail
Cap
Different Types of RNAsDifferent Types of RNAs
Messenger RNA (mRNA): Encodes protein sequences. Each three-nucleotides group, called a codon, translates to an amino acid (the protein building block).
Transfer RNA (tRNA): Decodes the mRNA molecules to amino acids. It connects to the mRNA with one side and holds the appropriate amino acid on its other side.
Ribosomal RNA (rRNA): Part of the ribosome, a machine for translating mRNA to proteins. It catalyzes (like enzymes do) the reaction that attaches the hanging amino acid from the tRNA to the amino acid chain being created.
What is a Code?What is a Code?• System by which information is represented by strings of coding symbols (length of strings is determined by the number of objects being represented)
•Enables the efficient transfer and storage of information
•Many different types in common usage, for example, ...
Braille
Morse Code
Ascii Code
• To encode n objects (items of information) using k coding symbols, strings of length logkn + 1 are needed.
• There are 20 amino acids used to make proteins. Which amino acids make up the protein to be produced are encoded in the RNA molecule. Since there are four bases {A,U,C,G} to use as coding symbols, the length of the code words must be at least log420 + 1 = 3 symbols long! The code words are called codons.
CodonsCodons
Codons Encode Amino Acids Codons Encode Amino Acids
The Genetic CodeThe Genetic Code
Of the 64 codons, 61 specify one of the 20 amino acids. The other 3 codons are chain-terminating codons and do not specify any amino acid. AUG, one of the 61 codons that specify an amino acid, is used in the initiation of protein synthesis.
Genetic Code RepresentationsGenetic Code Representations
Translation BasicsTranslation Basics
•Translation is mediated by the ribosome.•Ribosome is a complex of protein and rRNA molecules.•Ribosome attaches to the mRNA at a translation initiation site.•Ribosome moves along the mRNA sequence and in the process constructs a sequence of amino acids (a polypeptide molecule) which is released and folds into a protein.
Ribosome build polypeptides
Figure 10.12A-C
Codons
tRNAmolecules
mRNA
Growingpolypeptide
Largesubunit
Smallsubunit
mRNA
mRNAbindingsite
P site A site
P A
Growingpolypeptide
tRNA
Next amino acidto be added topolypeptide
mRNA, a specific tRNA, and the ribosome subunits assemble during initiation
1
Initiator tRNA
mRNA
Startcodon Small ribosomal
subunit
2
P site
Largeribosomalsubunit
A site
Figure 10.14
1 Codon recognition
Amino acid
Anticodon
AsiteP site
Polypeptide
2 Peptide bond formation
3 Translocation
Newpeptidebond
mRNAmovement
mRNA
Stopcodon
DNAdoublehelix(2-nmdiameter)
Metaphase chromosome
700nm
Tight helical fiber(30-nm diameter)
Nucleosome(10-nm diameter)
Histones
“Beads ona string”
Supercoil(200-nm diameter)
Mutations in DNAMutations in DNA
What is a Mutation?
A mutation is a permanent change in the DNA sequence of a gene. Mutations in a gene's DNA sequence can alter the amino acid sequence of the protein encoded by the gene. How does this happen? Like words in a sentence, the DNA sequence of each gene determines the amino acid sequence for the protein it encodes. The DNA sequence is interpreted in groups of three nucleotide bases, called codons. Each codon specifies a single amino acid in a protein. Mutations introduce genetic diversity into populations and facilitate the processes of natural selection and evolution.
DNA substitution (point) mutations are of two types. Transitions are interchanges of purines (A and G) or of pyrimdines (C and T), which therefore involve bases of similar shape. Transversions are interchanges between purine and pyrmidine bases, which therefore involve exchange of one-ring and two-ring structures. Although there are twice as many possible transversions, because of the molecular mechanisms by which they are generated, transition mutations occur at higher frequency than transversions.
Transitions and TransversionsTransitions and Transversions
Defined at DNA level
Point mutationsPoint mutations
Defined at codon level
Defined at protein level
Questions About DNAQuestions About DNA Given a string of nucleotides, determine if there are similar
sequences in the database.
Given a string of nucleotides, determine if it is informational: (1) find exons, (2) find splice junctions, (3) find promoters, (4) find regulatory sequences, and (5) evaluate for taxa-specific codon bias (different organisms often show particular preferences for one of the several codons that encode the same given amino acid; how these preferences arise is a much debated area of molecular evolution).
Given a string of nucleotides, find RNA secondary structure.
Given a string of nucleotides, find repeated sequences.
Questions About ProteinsQuestions About Proteins
Given a strings of amino acids, determine if similar sequences are in the database.
Given a strings of amino acids, predict secondary structure.
Given a strings of amino acids, predict interactions with other macromolecules, i.e. identify sequence motifs.
Given a strings of amino acids, predict function.