1. 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 (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.

3. The Cell: Storehouse of Hereditary/Genetic Information

4. 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.

5. Protein 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

8. Amino Acid Families

9. DNA and RNA are polymers of nucleotides
DNA is a nucleic acid, made of long chains of nucleotides
Phosphate group
Nitrogenous base
Nitrogenous base (A, G, C, or T)
Sugar
Phosphate group
Nucleotide
Thymine (T)
Sugar (deoxyribose)
DNA nucleotide
Polynucleotide
Sugar-phosphate backbone

10. DNA has four kinds of bases: A, T, C, and G
Thymine (T)
Cytosine (C)
Adenine (A)
Guanine (G)
Pyrimidines
Purines
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
= GTTAGCT

11. Partial chemical structure
Three Representations of DNA
Hydrogen bond
Ribbon model
Partial chemical structure
Computer model
Figure 10.3D

12. The Human Genome 22 pairs of chromosomes called autosomes
Two sex chromosomes (X,Y): XY in males and XX in females

13. Relative Size of Genomes

15. Genes: The Functional Part of 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.

16. Structure of Genes

17. Introns and Exons in Genes
Exons: coding regions of genes
Introns: noncoding regions (“junk” DNA)

18. Nitrogenous base (A, G, C, or U)
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
Nitrogenous base (A, G, C, or U)
Phosphate group
Uracil (U)
Sugar (ribose)
Figure 10.2C, D

19. Questions 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.

20. Questions 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.

21. The “Central Dogma” of Molecular 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.

22. Central Dogma of Molecular Biology (in flowchart form)

23. The “Central Dogma” in Prokaryotes and Eukaryotes

24. Transcription Basics GATTACA GAUUACA
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

25. In transcription, the DNA helix unzips
RNA polymerase
In transcription, the DNA helix unzips
DNA of gene
Promoter
DNA
Terminator
DNA
Initiation
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
Elongation
Area shown in Figure 10.9A
Termination
Growing RNA
Completed RNA
RNA polymerase

26. Eukaryotic RNA is processed before leaving the nucleus
Exon
Intron
Exon
Intron
Exon
DNA
Noncoding segments called introns are spliced out
A cap and a tail are added to the ends
Transcription Addition of cap and tail
Cap
RNA transcript with cap and tail
Introns removed
Tail
Exons spliced together
mRNA
Coding sequence
NUCLEUS
CYTOPLASM

27. Different 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.

28. 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, ...

29. Braille

30. Morse Code

31. Ascii Code

32. To encode n objects (items of information) using k coding symbols, strings of length logkn are needed.

33. There are 20 amino acids used to make proteins
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 log = 3 symbols long! The code words are called codons.

34. Codons

35. Codons Encode Amino Acids

36. The 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.

37. Genetic Code Representations

40. Translation 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.

41. Ribosome build polypeptides
Next amino acid to be added to polypeptide
Growing polypeptide
tRNA
molecules
P site
A site
Growing polypeptide
Large subunit
tRNA P A
mRNA
mRNA binding site
Codons
mRNA
Small subunit
Figure 10.12A-C

42. mRNA, a specific tRNA, and the ribosome subunits assemble during initiation
Large ribosomal subunit
Initiator tRNA
P site
A site
Start codon
Small ribosomal subunit
mRNA 1 2

43. Amino acid
Polypeptide
A site
P site
Anticodon
mRNA 1
Codon recognition
mRNA movement
Stop codon
New peptide bond 2
Peptide bond formation 3
Translocation
Figure 10.14

44. DNA double helix (2-nm diameter)
Histones
“Beads on a string”
Nucleosome (10-nm diameter)
Tight helical fiber (30-nm diameter)
Supercoil (200-nm diameter)
700 nm
Metaphase chromosome

45. Mutations 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.

46. Transitions and Transversions
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.

47. Point mutations Defined at DNA level Defined at codon level
Defined at protein level

48. Questions 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.

49. Questions 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.