Genetic Code and Central Dogma of Molecular Biology

• The genetic code and central dogma of molecular biology involves the flow of genetic information within biological systems.

The Central Dogma

• DNA stores genetic information.
• RNA is a transient copy of the information in DNA.
• Ribosomes use the information in RNA to synthesize proteins.
• The process includes replication (DNA -> DNA), transcription (DNA -> RNA), and translation (RNA -> Protein).

Genetic Code

• The code allows conversion of information from one form to another.
• The genetic code is part of the DNA molecule and carries instructions to build a protein.
• Information in DNA is stored in a sequential order of nucleotides, forming three-letter words called codons.
• Each codon is specific for an amino acid.
• Amino acids are the building blocks of proteins.
• DNA codes for the sequence of amino acids in a protein.

Transcription

• This creates a copy of DNA in the form of mRNA.
• Uracil is used in RNA instead of thymine.
• Ribose is used in RNA instead of deoxyribose.
• These changes make RNA less stable than DNA.
• The antisense strand of DNA serves as the template to create RNA.
• The coding strand of DNA has the same sequence as mRNA.
• DNA is more stable than RNA.

Codons

• Codons are three-letter words in the genetic code.
• They translate a nucleotide sequence into an amino acid sequence.
• Translation requires identifying the "start" and "end" of the sequence.
• The "start" codon is AUG in mRNA (encodes methionine; ATG in DNA coding strand).
• The "stop" codons are UAA, UAG, and UGA in mRNA.
  • There are three corresponding stop codons in DNA coding strand: TAA, TAG, and TGA.
  • Stop codons do not code for an amino acid, they signal the end of building a protein

Reading Frame and Codon Degeneracy

• The continuous stretch of codons begins with the start codon and ends in the stop codon.
• There are 3 nucleotides in each codon.
• With 4 nucleotides (A, T, C, G), there are 4^3 = 64 possible codons.
• Only 20 amino acids are commonly used to make proteins meaning some amino acids are coded by multiple codons.
• Changing the last nucleotide can still code for the same amino acid because the last nucleotide is in the wobble position.

Protein Structure

• The sequence of amino acids is the primary structure of a protein.
• Once formed, the protein folds into secondary structures (α-helices or β-sheets).
  • Secondary structures are maintained by hydrogen bonding.
• Tertiary structure involves interactions of amino acid side chains.
• Quaternary structure involves joining multiple polypeptide chains.
• The structure of a protein determines its function.
• Altering the structure of a protein can result in a non-functional protein or a protein with a different function.
• The sequence of amino acids affects the primary structure, which affects protein function.
• Changes to amino acids can disrupt hydrogen bonds needed for structure.
• Oxytocin is a peptide hormone produced by the hypothalamus and pituitary with roles in social bonding, sexual reproduction, and childbirth.
• Many proteins have a signal peptide that directs the ribosome to dock to the rough ER.
  • The initial methionine is cleaved off, and cysteine amino acids form disulfide bonds.

Summary

• The sequence of nucleotides stores information in DNA and codons.
• Codons are three nucleotides long, each specific to an amino acid.
• The sequence of nucleotides determines the amino acid sequence, which determines protein function.
• Changes in nucleotide sequence can result in altered or non-functional proteins.

Translation: Making Proteins

• The sequence of nucleotides in DNA holds the code for the sequence of amino acids in a protein.
• Transcription creates an mRNA copy from DNA.
• mRNA leaves the nucleus for the cytoplasm.
  • The mRNA includes a 5'Cap, the coding sequence, and a Poly A Tail.
• Ribosomes facilitate translation to produce the amino acid sequence.

Translation

• This is protein synthesis by the ribosomes using mRNA to create an amino acid sequence and occurs in the cytoplasm
• mRNA is a copy of DNA.
• rRNA makes up ribosomal subunits.
  • Ribosomal subunits are composed of rRNA and proteins.
  • The small subunit binds the mRNA.
  • The large subunit catalyzes peptide bond formation.
• tRNA contains an anticodon and an attached amino acid, and brings the correct amino acid to the ribosome.
• Each site in the ribosome has a specific function
  • A (Aminoacyl-tRNA) site is where the tRNA delivers the correct amino acid
  • P (Peptidyl-tRNA) site is where the peptide bond is formed, and the amino acids link
  • E (Exit) site is where the tRNA exits

Anticodon

• The anticodon is the 3-letter code found on tRNA which is complementary to the codon on mRNA
• Wobble effect describes how only first two nucleotides bind strongly

Wobble Effect

• Only the first two nucleotides in the codon-anticodon pairing bind strongly.

Translation

• First, assemble ribosomes around mRNA and attach tRNA to the start codon
• Then transfer amino acid to the next tRNA and move the ribosome to the next mRNA codon, and repeat
• Lastly, reach the stop codon and separate the ribosome, mRNA, and tRNA

Steps to initiate translation

• Attach the small ribosomal subunit to mRNA (binding to 5’ cap on mRNA).
  • Untranslated regions (ULR) are before/after the start codon, scans mRNA until it sees the start codon (AUG).
• The initiator tRNA with anticodon UAC binds to the start codon and has methionine attached. That tRNA occupies 1 of the tRNA binding sites on the ribosome
• The large ribosomal subunit binds.
  • The tRNA occupies 1 of the tRNA binding sites on the ribosome, creating the initiation complex.

Elongation of Translation

• The second tRNA binds to the next codon and brings in the next amino acid.
  • Peptide bond formation is catalyzed by the large ribosomal subunit.
• The ribosome moves to the next codon.
  • The first amino acid is separated from its tRNA.
  • The first tRNA is released from the ribosome.
  • The ribosome can now accept another tRNA.
• Polypeptide strand grows one amino acid at a time.

Termination of Translation

• The ribosome reaches a stop codon.
  • The stop codons (UAA, UAG, UGA) have no matching tRNA.
• Release factors bind to separate the complex.
  • The polypeptide chain (protein) is released from the ribosome.
  • The MRNA released from ribosome
  • Then the small and large ribosomal subunits separate.
• The ribosome and mRNA can be reused.
• The tRNA can be recycled by adding back an amino acid.

Polypeptide Modification

• The newly synthesized polypeptide can remain in the cytoplasm, or enter the rough endoplasmic reticulum.
• A signal peptide directs the ribosome to dock to rough ER.
  • The first 4 to 12 amino acids removed.
• Some proteins need to be secreted outside the call, and must be modified to function properly by breaking them into smaller polypeptides, adding sugars, and phosphates.

Polysomes

• Many ribosomes can translate the same mRNA at the same time
• A cell may require a lot of a certain protein

Translation Summary

• Translation uses the mRNA nucleotide sequence to create a protein amino acid sequence
• The small ribosomal subunit binds to mRNA and moves to the start codon
• tRNA anticodon binds to the complementary codon sequence
• The large ribosomal subunit binds and catalyzes the peptide bond between two amino acids
• The Ribosome translocates along mRNA, and tRNA brings in more amino acids
• The Ribosome repeats this process until it reaches a stop codon
• The stop codon does not have an associated
• Then the Ribosomal subunits, mRNA & tRNA all separate
• Proteins requiring modification are inserted into RER during synthesis

Cell Division

• Before a cell can divide, the nucleus must divide.
• Mitosis maintains the same number of chromosomes in daughter cells.
  • Mitosis occurs in somatic (body) cells.
• Meiosis halves the number of chromosomes in daughter cells.
  • Meiosis occurs in germ (reproductive) cells.
• After nuclear division, the cytoplasm must be divided.

Mitosis: Genetically Identical Cells

• Mitosis results in genetically identical cells.
• The goal of mitosis is to allow a cell to divide such that:
  • Two cells from a single cell are created.
  • Daughter cells are exact copies of the parent cell.
  • The number of chromosomes remains the same.
• Mitosis serves purposes such as organism growth, replacement of damaged somatic cells, and asexual reproduction.

Chromosome Structure

• Chromosomes are double- stranded DNA molecules attached to histone proteins and different species have a different number of chromosones.
• Before mitosis, each chromosome must be duplicated.
• Sister chromatids are the two copies of the same DNA molecule, remaining together until late mitosis and centromeres hold sister chromatids together

The Cell Cycle

• The cell cycle is the series of events that take place in a cell that cause it to divide into two daughter cells.
• These steps include:
  • Interphase (G1, Synthesis, Gap 2)
  • Mitosis (prophase, metaphase, anaphase, telophase)
  • Cytokinesis

Interphase

• Interphase is the longest portion of the cell cycle where cell increases in mass, duplicates cellular components, duplicates DNA

Cell Division Controls

• Cells remain in G1 until a growth factor signals the cell to divide meaning those cells will remain in G1

Checkpoints

• Checkpoint is a control mechanism in the cell cycle where if problems happen the cycle will stop
• Genetic mutations resulting in uncontrolled growth cells, if checkpoints malfunction, the cell can loose control of the cycle and cells will continuously divide
• Sum of all the chromosomes

Chromosome Number

• Each species has different chromosome numbers
• Humans have a total of 46 chromosomes
• Diploid cells have two of every chromosome.
• Humans have 23 pairs of chromosomes, inheriting one set from each parent.
• Homologous chromosomes have the same genes in the same locations along the chromosome.
• Sister chromatids are exact copies of chromosomes, whilst homologous chromosomes contain same genes but they are not exact copies (two copies of homologous)
• Sister are created in S phase

Human Chromosomes

• Unduplicated human chromosomes are in pairs
• Numbered by length.
• Chromosome 1 (longest) - 22 (shortest). There is one sex chromosome per set (chromosome 23).
• The appearance of duplicated homologues is as bellow
  • XX for female.
  • XY for male, and Y is much shorter.

Mitosis

• Two complete sets of genetic information Mitosis Diploid “parent” cells must create two diploid “daughter cells” don’t randomly split 46 to a daughter cell Cells divide to have 2 complete sets of unduplicated chromosomes

Mitosis Division: Genetic Variation

• Replicate as S, for both homologous chromosomes
• One and One gets in each 1 in each chromosome
• Mitosis cells is the process of duplicating the cycle, DNA controls cycles that controls dups in S cycles

13: Mitosis

• Cell division gives rise to identical cells with division, this involves cellar and DNA problems that are fixed with mitosis.
• Cell Problems include what to do with the cell, that are fixed with membrane remove and dividing contents to each side.
• DNA has to go thought steps to fix their problems
• M phase occurs after cycle in interphase
• Phase occurs in 5 steps

Mitosis Phases

• Prior , DNA is undrawled inside the nucleus to the phase to start
• In early the chromosome condensate with two centers
• Centromeres move after early break down phase
• Transition develops kinetochore
• Nucleus is gone
• Centrosomes move to opposite sites cells.
• Metaohase, all are connected Anaphase,
• Separation occurs Two diploid , move to side poles (2 cells divided ) Teleophase Opposite pole Begins, mitotic stops Envelop forms on grouping chromoesmes, Cytokinesis Daughter will all, Same, undup and condense etc, on nuclei Eqqual amounts to cells, Cytokineses, divisions cotnenrs Aniamkl, has to Force, cont ring, is required to pinch two ocnes

Plant versus Amino Mitosis

• Viescles is used to wall in plants.

• Mitosis is used here too and has has celluar steps, nuclear mom remove, sep dupls,DNA is then seperated

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Alleles

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Sexual REproduciton

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• di, attached,

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Summary

• The human genome (i.e. chromosome structure)
• Duplicated homologous chromosomes line up (2n).
• Homologous chromosomes are separated (not sister chromatids).
• Results in two haploid daughter cells (n).
• Sister chromatids still attached at centromere.

SEXUAL REPRODUCTION

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