Understanding Gene Expression

• Gene expression changes moment by moment, reflecting the body's current needs.
• The demonstrated expression is usually appropriate for that moment's feelings.
• Gene expression is the use of a gene whose product is necessary for that moment.
• Gene expression provides a particular protein when needed, whether during development, increased anxiety, or in response to environmental changes.

Gene Expression

• Each cell has at least 20,000 genes, and all cells contain the same genes.
• Cells have different structures and functions because they express different genes.
• Gene expression describes using a gene to make a protein.

Regulation of Gene Expression

• Gene expression is regulated to ensure the correct proteins are made when and where they are needed.
• Regulation can occur at any stage, from the start of transcription to the processing of a protein after translation.
• Regulation of gene expression occurs at the following stages:
• Chemical and structural modification of DNA or chromatin.
• Transcription.
• Translation.
• Post-transcriptional modification.
• RNA transport.
• mRNA degradation.
• Post-translational modifications.
• Regulatory proteins, or transcription factors, bind to DNA to control transcription.
• Transcription factors bind to cis-regulatory elements (part of the DNA) to switch a gene on (activator) or off (repressor).
• RNA polymerase transcription is regulated by at least five mechanisms:
• Transcription factors alter the specificity of RNA polymerase for a promoter, affecting its binding and transcription initiation.
• Activator proteins enhance the interaction between RNA polymerase and a promoter.
• Repressor proteins bind to non-coding sequences near the promoter, impeding RNA polymerase's progress.
• Basal factors help position RNA polymerase at the start of a gene.
• Enhancers, bound by activators, loop DNA to bring specific transcription factors to the initiation complex.
• The initiation complex is composed of RNA polymerase and numerous transcription factors.
• A mutation in a cis-regulatory region (e.g., the promoter) can keep a gene permanently off or on.

Mutations and Albinism

• Albinism results from a mutation in a gene for melanin, a protein found in skin and eyes.
• The mutation can stop melanin production or significantly reduce the amount produced.
• A mutation is a change in the sequence of bases in DNA.
• Mutations are essential for evolution, and the ultimate source of new genetic material.
• Most mutations have no effect, but some are beneficial.
• Even harmful mutations rarely cause drastic changes.

Types of Mutations

• Germline mutations occur in gametes and can be transmitted to offspring, affecting every cell.
• Somatic mutations occur in other body cells, potentially having little effect on the organism, and are not passed to offspring.
• Mutations also differ in how the genetic material is changed.
• Mutations may change the structure of a chromosome or just change a single nucleotide.

Chromosomal Alterations

• Chromosomal alterations are mutations that change chromosome structure.
• They occur when a section of a chromosome breaks off and rejoins incorrectly or does not rejoin at all.
• Types of chromosomal mutations include:
• Deletion: Loss of a DNA segment.
• Duplication: Repetition of a DNA segment.
• Inversion: A DNA segment is flipped and reattached.
• Insertion: A segment of DNA from one chromosome is added to another.
• Translocation: Segments from different chromosomes switch positions.
• Chromosomal alterations can be very serious, resulting in death or multiple effects if the organism survives.

Point Mutations

• A point mutation is a change in a single nucleotide in DNA.
• These mutations are usually less serious than chromosomal alterations.
• Point mutations can be silent, missense, or nonsense mutations.
• Silent mutations: The mutated codon codes for the same amino acid (e.g., CAA → CAG, both for glutamine), resulting in no change.
• Missense mutations: The mutated codon codes for a different amino acid (e.g., CAA → CCA, glutamine to proline), with variable effects.
• Nonsense mutations: The mutated codon becomes a premature stop codon (e.g., CAA → UAA, glutamine to stop), which is usually serious.

Frameshift Mutations

• Frameshift mutations: Include a deletion or insertion of nucleotides that changes the reading frame of the base sequence.
• Insertions: Add nucleotides.
• Deletions: Remove nucleotides.
• Example of a frameshift mutation:
• Original sequence: AUG-AAU-ACG-GCU (start-asparagine-threonine-alanine)
• Insertion of A after AUG: AUG-AAA-UAC-GGC-U (start-lysine-tyrosine-glycine)
• Frameshift mutations can dramatically change how codons in mRNA are read, drastically affecting the protein product.

Albinism and Natural Selection

• Albinism is not commonly seen in nature because the resulting lack of pigmentation often lowers an organism's ability to camouflage themselves to their environment.
• The lack of pigmentation can make albino organisms more vulnerable and easier targets for predators.

Protein Synthesis

• Protein synthesis is the process of making proteins, which are essential and involved in transport, structure, enzymes, and protection.
• DNA contains the genetic information coding for proteins.

DNA and RNA

• DNA is in the nucleus, with some coding for active proteins.
• RNA carries information from genes out of the nucleus for protein production.
• RNA is a nucleic acid similar to DNA, but its role in protein synthesis is significant.

Transcription and Translation

• Protein synthesis involves two major steps: transcription and translation. Transcription: DNA is transcribed into a message (mRNA) in the nucleus. Translation: The message is translated into a protein.
• Transcription precedes translation.
• During transcription, RNA polymerase connects complementary RNA bases to DNA, forming a single-stranded mRNA.
• mRNA undergoes significant editing.
• In eukaryotes, mRNA leaves the nucleus and attaches to a ribosome in the cytoplasm.
• Ribosomes, made of rRNA, build proteins.

Translation Details

• In the cytoplasm, tRNA molecules carry amino acids, the building blocks of proteins.
• mRNA directs which tRNAs come in and transfer their amino acids.
• tRNA reads mRNA bases in triplets called codons.
• The tRNA anticodon is complementary to the mRNA codon.
• Example: mRNA codon AUG pairs with tRNA anticodon UAC, which carries methionine.
• A codon chart indicates which amino acid each mRNA codon codes for.
• AUG is the start codon, typically coding for methionine as the first amino acid.
• Multiple codons can code for the same amino acid.
• Amino acids are held together by peptide bonds.
• At the end of mRNA, a stop codon signals the end of protein building.
• DNA is the ultimate director of protein building, with the help of mRNA, rRNA, and tRNA.
• Protein folding and modification may occur, followed by transport.

Central Dogma of Molecular Biology

• Central Dogma of Molecular Biology: Genetic instructions in DNA are copied by RNA, which carries them to a ribosome where they are used to synthesize a protein.
• DNA and RNA provide genetic directions to cells.
• DNA contains instructions for making proteins.
• RNA carries information from DNA to ribosomes where proteins are made.
• Transcription: Genetic information is transferred from DNA to RNA.
• Translation: The information from RNA is used to create proteins.

Key Terms Defined

• Protein Synthesis: Process in which cells make proteins that includes transcription of DNA and translation of mRNA.
• Genetic Code: Universal code of three-base codons that encodes the genetic instructions for the amino acid sequence of proteins.
• Codon: Group of three nitrogen bases in nucleic acids that makes up a code “word” of the genetic code and stands for an amino acid, start, or stop.
• Transcription: Genetic instructions in DNA are copied to form a complementary strand of mRNA.
• Translation: Genetic instructions in mRNA are “read” to synthesize a protein.
• RNA Polymerase: An enzyme that helps produce RNA during transcription.
• Messenger RNA (mRNA): Copies genetic instructions from DNA in the nucleus and carries them to ribosomes in the cytoplasm.
• Ribosomal RNA (rRNA): Helps form ribosomes and assemble proteins.
• Transfer RNA (tRNA): Brings amino acids to ribosomes where they are joined together to form proteins.
• Promoter Site: Region of a gene where a RNA polymerase binds to initiate transcription of the gene.
• Introns: Non-coding regions of mRNA that are removed by splicing.
• Extrons: Coding regions.

DNA, RNA and Protein

• During protein synthesis, protein is built one amino acid at a time.
• DNA determines the order of amino acids.
• DNA has four nitrogen bases: A, T, C, and G.
• Codons are groups of three bases that code for an amino acid or a start/stop signal.

Role of RNA

• Proteins are synthesized in ribosomes of the rough endoplasmic reticulum, while DNA remains in the nucleus.
• RNA transfers DNA instructions to the ribosomes.
• RNA codons are complementary to DNA codons, with uracil (U) replacing thymine (T).

Three Main Types of RNA

• Messenger RNA (mRNA): Copies genetic instructions from DNA and carries them to ribosomes.
• Ribosomal RNA (rRNA): Helps form ribosomes.
• Transfer RNA (tRNA): Brings amino acids to ribosomes.
• While DNA can make protein, protein cannot make DNA.

Reading the Genetic Code

• Start codon (AUG) indicates where to begin reading the code.
• Group three letters at a time from AUG.
• Stop codons (UAG, UGA, UAA) signal protein synthesis to stop and do not code for any amino acids.
• The genetic code is redundant with 64 possible codons coding for only 20 amino acids.

Transcription Process

• Transcription makes mRNA complementary to the DNA template.
• Initiation: RNA polymerase binds to the promoter and DNA unwinds.
• Elongation: RNA polymerase adds complementary nucleotides to the mRNA strand.
• Termination: The pre-mRNA strand detaches from the DNA.

Processing mRNA

• Pre-mRNA is modified before leaving the nucleus.
• Splicing removes introns from the pre-mRNA.
• The mature mRNA proceeds to translation.

Translation Process

• mRNA moves to a ribosome.
• tRNA carries anticodons complementary to mRNA codons providing the materials.
• tRNA gives up its amino acid.
• The ribosome builds the protein until it reaches a stop codon.

RNA Structure

• RNA is typically single-stranded, made of ribonucleotides linked by phosphodiester bonds.
• A ribonucleotide has ribose sugar, a nitrogenous base (A, U, G, C), and a phosphate group.
• RNA is less stable than DNA, making it suitable for short-term functions.
• Uracil (U) in RNA pairs with adenine (A).
• RNA shows intramolecular base pairing, creating a three-dimensional structure.

RNA Functions in Protein Synthesis

• Cells use RNA to direct protein synthesis (translation) from DNA instructions.
• Proteins build cellular structures and serve as enzymes for chemical reactions.

Types of RNA

• Messenger RNA (mRNA): An intermediary between DNA and protein, used by the ribosome to direct protein synthesis.
• Ribosomal RNA (rRNA): Ensures proper alignment of mRNA, tRNA, and the ribosome during protein synthesis; also catalyzes peptide bond formation.
• Transfer RNA (tRNA): Carries the correct amino acid to the protein synthesis site in the ribosome.
• François Jacob and Jacques Monod hypothesized mRNA as an intermediary between DNA and protein products in 1961.

mRNA Function

• mRNA carries the message from DNA, controlling cellular activities.
• Gene for a protein is "turned on" and mRNA is synthesized through transcription.
• mRNA interacts with ribosomes to direct protein synthesis (translation).
• mRNA is relatively unstable and short-lived, ensuring proteins are only made when needed.

rRNA and tRNA Function

• rRNA and tRNA are stable types of RNA encoded in DNA.
• In eukaryotes, rRNA synthesis and assembly occur in the nucleolus of the nucleus, and tRNA synthesis and assembly occur in the cytoplasm of prokaryotes.
• Ribosomes are composed of rRNA and protein.
• rRNA is a major constituent of ribosomes, ensuring proper alignment and catalyzing peptide bond formation.
• Peptidyl transferase is the enzymatic activity of rRNA.

Importance of tRNA

• tRNA carries the correct amino acid to the protein synthesis site in the ribosome.
• Base pairing between tRNA and mRNA allows the correct amino acid to be inserted.
• Mutations in tRNA or rRNA can cause global cell problems.

RNA as Hereditary Information

• RNA acts as hereditary information for many viruses lacking DNA.
• Rhinoviruses, influenza viruses, and Ebola virus are single-stranded RNA viruses.
• Rotaviruses are double-stranded RNA viruses and cause severe gastroenteritis in children.
• Double-stranded RNA is uncommon in eukaryotic cells, indicating viral infection.