BIO152 L5-L8: Mendel, Molecular Basis of Inheritance, Gene Expression, and Natural Selection

Mendel Chap 14 May 21st, 2025

• Reginald C Punnett created the Punnett Square to visualize offspring possibilities in genetic crosses.
• Genetic Traits:
• Widow’s Peak and Cleft chin are dominant traits.
• Attached earlobes are a recessive trait (more complex).
• Dominant traits show up even if you get it from just one parent, while recessive traits only show up in certain events.

Chapter 14 | Key Concepts

• Mendel used the scientific approach to identify two laws of inheritance.
• The laws of probability govern Mendelian inheritance.
• Inheritance patterns are often more complex than predicted by simple Mendelian genetics.
• Many human traits follow Mendelian patterns of inheritance.

Mendel and the Scientific Approach

• Pea plants were advantageous for genetic study because:
• They were available in many different varieties.
• Varieties have distinct heritable features, or characters (e.g., flower color).
• Each variant for a character, such as purple or white flowers, is called a trait.

Why the Pea Plant?

• Easily categorizable characters.
• Easy to control pollination.
• Short generation time.
• Large number of offspring (lots of grow really fast so you can have a lot of them & more seeds = more plants to make).

Crossing Pea Plants: Generations

• In a typical experiment, Mendel mated two contrasting, true-breeding varieties, a process called hybridization.
• True-breeding parents are the P generation.
• Hybrid offspring of the P generation are called the F1 generation.
• When F1 individuals self-pollinate or cross-pollinate with other F1 hybrids, the F2 generation is produced (crossing traits together).

Inquiry: F1 Hybrid Pea Plant Traits

• When Mendel crossed F1 hybrids, many F2 plants had purple flowers, but some had white.
• He discovered a ratio of about 3 to 1, purple to white flowers, in the F2 generation.

The Law of Segregation

• Mendel reasoned that only the purple flower factor was affecting flower color in F1 hybrids.
• Mendel called purple flower color a dominant trait and white flower color a recessive trait.
• The factor for white flowers was not diluted or destroyed because it reappeared in the F2 generation (as long as purple plants did show up & didn't show up all the time).

The Law of Segregation & Genes

• Mendel observed the same pattern of inheritance in six other pea plant characters [each represented by two traits].
• What Mendel called a heritable factor is now called a gene.

Alleles

• Alternative versions of a gene are called alleles.
• Each gene resides at a specific locus on a specific chromosome.

Mendel’s Law of Segregation & Punnett Squares

• Punnett square: a diagram for predicting the results of a genetic cross between individuals of known genetic makeup.
• Visualization of genotypes [and phenotypes] for simpler hybrid and dihybrid crosses.
• Gets too complicated for 3+ traits.

Useful Vocabulary

• Homozygous: An organism with two identical alleles for a character is homozygous for the gene controlling that character.
• Heterozygous: An organism that has two different alleles for a gene is heterozygous for the gene controlling that character.
• Unlike homozygotes, heterozygotes are not true-breeding.
• Phenotype: An organism’s traits (visible trait).
• Genotype: An organism’s genetic makeup (exact allele).

Phenotype vs Genotype

• In the example of flower color in pea plants, PP and Pp plants have the same phenotype [purple], but different genotypes.

Research Method: The Testcross

• A testcross can be done to determine the genotype of an individual with a dominant phenotype.
• This involves breeding the mystery individual with a homozygous recessive individual.
• If any offspring display the recessive phenotype, the mystery parent must be heterozygous.

The Laws of Probability Govern Mendelian Inheritance

• The probability of true-breeding (homozygous) offspring can be calculated using Mendelian ratios.
• The genotype ratios from the cross Gg x Gg are: $frac{1}{4} GG : frac{1}{2} Gg : frac{1}{4} gg$
• The F2 homozygous/true-breeding offspring [GG and gg] are half the progeny.

Analyzing Pedigrees

• Pedigree analysis can give clues about the inheritance of a trait.
• Unaffected parents giving rise to an affected offspring is a sign of a recessive trait.
• Affected parents with unaffected offspring could indicate a dominant trait.

Albinism: A Recessive Trait

• Albinism is an example of a recessive trait that requires both parents to contribute the recessive allele.
• Normal phenotype parents (Aa) can have offspring with albinism (aa).

Pedigree Analysis Symbols

• Normal Female/Male
• Mating
• Affected Individual
• Siblings

Learning Catalytics – Question #3

• To determine probability of next child having a trait, analyze parents: A heterozygous cross (Aa x Aa) indicates a 25% chance that the next child will be affected (aa).

Learning Catalytics – Question #5

• If both parents are carriers (heterozygotes), the chance of children inheriting the dominant trait is 3/4.

Question on Tay Sach’s Disease

• If both parents are carriers (Aa), a cross shows 2/3 are carriers.

Pleiotropy

• Pleiotropy = one gene, many effects.
• Most genes have multiple phenotypic effects.
• Pleiotropic alleles are responsible for multiple symptoms of some hereditary diseases, such as cystic fibrosis and sickle-cell disease.

Extending Mendelian Genetics for Multiple Genes

• Inheritance by two genes may deviate from simple Mendelian patterns.
• Some traits may be determined by two or more genes.
• Epistasis: A gene at one locus alters the phenotypic expression of a gene at a second locus.
• Example - in Labrador retrievers and many other mammals, coat color depends on two genes.
• Polygenic Inheritance: Additive effect of two or more genes on a single phenotype.

Epistasis Example

• One gene determines pigment color (alleles B for black and b for brown).
• The other gene (with alleles E for deposition) determines whether pigment will be deposited in the hair.
• Gene E/e is epistatic to B/b and therefore the coat color is determined by the E/e locus.

Polygenic Inheritance Examples

• Quantitative characters are those that vary in the population along a continuum.
• Quantitative variation usually indicates polygenic inheritance, an additive effect of two or more genes on a single phenotype.
• Examples: Skin color, hair color, height, intelligence, blood pressure, obesity, autism

Multifactorial Disorders

• Many diseases, such as heart disease, diabetes, alcoholism, mental illnesses, and cancer have both genetic and environmental components.
• No matter the genotype, lifestyle has a tremendous effect on phenotype.
• Little is understood about genetic contribution to most multifactorial diseases.

Pedigree Analysis

• A pedigree is a family tree describing interrelationships of parents and children across generations.
• Inheritance patterns of particular traits can be traced and described using pedigrees.

Cystic Fibrosis

• Most common lethal genetic disease in Canada affecting 1/2,500 people of European descent.
• Due to defective or absent chloride transport channels in plasma membranes leading to a buildup of chloride ions outside cell.
• Symptoms from mucus buildup and abnormal absorption of nutrients in the small intestine.

Sickle-Cell Disease: A Genetic Disorder with Evolutionary Implications

• Sickle-cell disease affects 1/400 African-Americans.
• Caused by the substitution of a single amino acid in hemoglobin protein in red blood cells.
• Symptoms include physical weakness, pain, organ damage, and even paralysis.
• In homozygous individuals, all hemoglobin is abnormal (sickle-cell).

Sickle-Cell Disease: Heterozygote Advantage

• Heterozygotes are usually healthy but may suffer some symptoms.
• About 1 /10 African Americans carries the sickle cell allele.
• Heterozygotes are less susceptible to the malaria parasite, so there is an advantage to being heterozygous where malaria is common.

Dominantly Inherited Disorders

• Some human disorders are caused by dominant alleles.
• Dominant alleles that cause a lethal disease are rare and arise by mutation.
• Achondroplasia is a form of dwarfism caused by a rare dominant allele.

Inheritance of Genetic Diseases - Examples

• Tay Sachs Disease [Autosomal Recessive]
• Cystic Fibrosis [Autosomal Recessive]
• Sickle Cell Anemia [Autosomal Recessive]
• Achondroplasia [Autosomal Dominant]
• Hemophilia A [X-Linked Recessive]
• Colour Blindness [X-Linked Recessive]

Analyzing Crosses

• A heterozygous inflated green pod plant crossed with a homozygous recessive constricted yellow pod plant yields four different phenotypes, each with a $frac{1}{4}$ probability.
• These are: inflated yellow, inflated green, constricted yellow, or constricted green.

Chromosomal Basis of Inheritance Chap 15 May 26th, 2025

Telomeres

• Greek telos meaning end
• Greek meros meaning part

Chapter 16 | Key Concepts

• DNA is the genetic material
• Many proteins work together in DNA replication and repair
• Chromosomes consist of a DNA molecule packed together with proteins

The Structure of a DNA Strand

• Nucleic acids are polymers called polynucleotides
• Each polynucleotide is made of monomers called nucleotides
• Nucleoside = nitrogenous base + sugar
• Nucleotide = base + sugar + phosphate group
• Nitrogenous base = Thymine, Guanine, Cytosine, Adenine

Building a Structural Model of DNA

• Maurice Wilkins and Rosalind Franklin used X-ray crystallography to study molecular structure.
• Rosalind Franklin produced a picture of the DNA molecule using this technique
• Franklin’s images of DNA enabled Watson to deduce that DNA was helical
• X-ray images also enabled Watson to deduce the width of the helix and the spacing of nitrogenous bases
• The pattern in the photo suggested that the DNA molecule was made up of two strands, forming a double helix

The Double Helix

• Sugar-Phosphate backbone have 5’end and 3’end
• Hydrogen bonds between Thymine-Adenine & Guanine-Cytosine keep two strands together
• Covalent bonds between nucleotides and sugar-phosphate backbone
• Van der Waals interactions help hold stacks together

The Double Helix

• Watson and Crick built models of a double helix to conform to the X-ray data and chemistry of DNA
• Franklin had concluded that there were two outer sugar-phosphate backbones, with bases paired in the molecule’s interior
• Watson built a model in which backbones were antiparallel [their subunits run in opposite directions]

The Double Helix

• At first, Watson and Crick thought bases paired like with like [A with A, and so on]  but no uniform width
• Pairs of purine with pyrimidine  uniform width consistent with X-ray data
• Watson and Crick reasoned that pairing was more specific, dictated by base structures

Base Pairing in DNA

• Adenine [A] paired only with thymine [T], and guanine [G] paired only with cytosine [C]
• The Watson -Crick model explains Chargaff’s rules: the amount of A = T, and the amount of G = C
• Hydrogen bonds determine melting temperature Tm of the molecule

Key Proteins in DNA Replication

• Topoisomerases: Break, swivel, and re-join the parental DNA ahead, relieving twisting strain from untwisting.
• Helicases: Unwind and separate the parental DNA strands.
• Primases: Synthesize RNA primer using parental DNA as template.
• Single-strand binding proteins: Bind to bases & stabilize the unwound parental strands.
• DNA polymerases: Add new nucleotides, proofread, repair DNA.
• DNA Pol I: Replaces the RNA with DNA.
• DNA Pol III: Adds DNA bases.
• DNA ligases: Join fragments.

Origin of Replication

• Replication bubble
• Two Template strands and Two New replication strands

Key Proteins in Initiation of DNA Replication

• Topoisomerases: Ahead of the replication bubble; break, swivel, and re-join the parental DNA ahead, relieving strain
• Helicases: At the replication fork; unwind and separate the parental DNA strands
• Primases: Bound to unwound, single strand; synthesis of RNA primer using parental DNA as template
• Single-strand binding proteins: Bind to bases; stabilize the unwound parental strands

Incorporation of a Nucleotide into a DNA Strand

• DNA polymerases add new nucleotides to the growing new strand at the 3’ end
• Two phosphate groups are released [pyrophosphate] which can split into inorganic phosphates

Antiparallel Elongation

• DNA polymerases add nucleotides only to the free 3′ end of a growing strand
• Therefore, a new DNA strand can elongate only in 5′ to 3′ direction

Synthesis: Leading Strands

• Each of the two template strands of DNA uses DNA polymerase III synthesizes a leading strand continuously, moving toward the replication fork.
• Only one DNA Pol III required for the whole strand

Synthesis: Lagging Strands

• To elongate other new strand, or lagging strand, DNA polymerases must work in the direction away from replication fork
• The lagging strand is synthesized as series of segments called Okazaki fragments, which are joined by DNA ligase

Synthesis: Lagging Strand Steps

1. Primase joins RNA nucleotides into a primer.
2. DNA Polymerase III adds DNA nucleotides to the primer, forming Okazaki fragment 1
3. After reaching the next RNA primer to the right, DNA Polymerase III detaches
4. Primase joins RNA into a primer for Fragment 2.
5. DNA Polymerase I replaces the RNA with DNA, adding nucleotides to the 3’ end of fragment 1 [later fragment 2]
6. DNA ligase forms a bond between the newest DNA and the DNA from fragment 1.

Summary of Bacterial DNA Replication

1. Helicase unwinds the parental double helix.
2. Molecules of single-strand binding protein stabilize the unwound DNA
3. The leading strand template uses DNA pol III to synthesize continuously in the 5’ to 3’ direction
4. The lagging strand template is primed by Primase before being synthesized discontinuously in the 5’ to 3’ direction using DNA pol III. DNA pol I removes the primer before DNA ligase joins the fragments.

Current Model of the DNA Replication Complex

• Loops of DNA go in and out

DNA Polymerases Proofread and Repair DNA

• DNA polymerases proofread newly made DNA, replacing any incorrect nucleotides
• In mismatch repair of DNA, repair enzymes correct errors in base pairing
• DNA can be damaged by exposure to harmful chemical or physical agents, and can also undergo spontaneous changes

Nucleotide Excision Repair of DNA Damage

• In nucleotide excision repair, a nuclease cuts out damaged stretches of DNA
• DNA polymerase fills in the correct/missing nucleotide
• DNA Ligase seals the free end to the existing DNA

Evolutionary Significance of Altered DNA Nucleotides

• Error rate after proofreading repair is low, but not zero
• Sequence changes may become permanent and can be passed to the next generation
• These changes [mutations] are source of genetic variation upon which natural selection operates

Replicating the Ends of DNA Molecules

• Limitations of DNA polymerase create problems for linear DNA of eukaryotic chromosomes
• The usual replication machinery provides no way to complete the 5′ ends
• Therefore, repeated rounds of replication result in shortening of DNA molecules at the ends
• Not a problem for prokaryotes, as most have circular chromosomes

Shortening of Linear DNA Molecules

• Eukaryotic chromosomal DNA molecules have special nucleotide sequences at their ends called telomeres
• Telomeres do not prevent shortening of, but they postpone erosion of genes near the ends of chromosomes
• It has been proposed that shortening of telomeres is connected to aging

Replicating the ends of DNA Molecules

• If chromosomes of germ cells became shorter in every cell cycle, essential genes would eventually be lost/missing from the gametes they produce
• An enzyme called telomerase catalyzes lengthening of telomeres in germ cells
• Shortening of telomeres might protect cells from cancerous growth; limit the number of cell divisions
• There is evidence of telomerase activity in cancer cells, which may allow cancer cells to persist.

Chromosomes, DNA, and Proteins

• Bacterial chromosomes are double-stranded, circular DNA molecules associated with small amounts of protein
• Eukaryotic chromosomes are linear DNA molecules associated with a large amount of protein
• In a bacterium, DNA is “supercoiled” and found in the nucleoid

Chromatin

• Chromatin, complex of DNA and protein, found in nucleus of eukaryotic cells
• Chromosomes fit into nucleus through an elaborate, multilevel system of packing

Impact: Painting Chromosomes

• Human chromosomes can be treated with special molecular tags that allow each pair of homologous chromosomes to be seen as a different colour

Analyzing Pedigrees: Autosomal Traits

• Recessive Traits Pedigrees: Affected person inherits two copies of the recessive allele
• Skips generations: carriers don’t express the trait but pass to offspring
• Males and females equally affected
• Dominant traits pedigrees: Only one copy of dominant allele is needed for trait expression
• No skipping of generations: affected individuals in every generation
• Males and females equally affected on the 22 chromosomes & not linked to the X or Y chromosome.

Key Concept: Probability Basics

• Sum Rule: Probability of outcome A or outcome B
• For example: What is the chance of being a carrier of a recessive trait?
• $p = ( frac{1}{3}) + ( frac{1}{3}) = frac{2}{3}$
• Product Rule: Probability of outcome A and outcome B
• For example: What is the chance of getting a son that is affected and a daughter that is also affected?
• $p = ( frac{1}{2}) * ( frac{1}{2}) = frac{1}{4}$

Analyzing Complex Inheritance Patterns

• The relationship between genotype and phenotype is rarely as simple as in the pea plant characters Mendel studied.
• Many heritable characters not determined by only one gene with two alleles.
• However, basic principles of segregation and independent assortment apply even to more complex patterns of inheritance

Extending Mendelian Genetics for a Single Gene

• Inheritance by a single gene may deviate from simple Mendelian patterns:
• When alleles are not completely dominant or recessive
• When a gene has more than two alleles
• When a gene produces multiple phenotypes

Degrees of Dominance

• Complete dominance: Phenotypes of the heterozygote and dominant homozygote are identical
• Incomplete dominance: Phenotype of F1 hybrids is in between the phenotypes of the two parental varieties
• Codominance: Two dominant alleles affect the phenotype in separate, distinguishable ways.

Multiple Alleles Example: ABO blood types

• The enzyme encoded by the IA allele adds the A carbohydrate.
• The enzyme encoded by IB allele adds the B carbohydrate
• The enzyme encoded by the i allele adds neither.
• i is recessive, IA and IB is codominance

Extending Mendelian Genetics for Multiple Genes (cont.)

• Inheritance by two genes may deviate from simple Mendelian patterns
• Some traits may be determined by two or more genes
• Epistasis: a gene at one locus alters the phenotypic expression of a gene at a second locus
• Example - in Labrador retrievers and many other mammals, coat colour depends on two genes
• Polygenic Inheritance: additive effect of two or more genes on a single phenotype

Epistasis Example

• One gene determines pigment colour (alleles B for black and b for brown)
• The other gene (with alleles E for deposition) determines whether pigment will be deposited in the hair
• Gene E/e is epistatic to B/b and therefore the coat colour is determined by the E/e locus

Autosomal Recessive Examples | Cystic Fibrosis

• Most common lethal genetic disease in Canada affecting 1/2,500 people of European descent
• Due to defective or absent chloride transport channels in plasma membranes leading to a buildup of chloride ions outside cell
• Symptoms from mucus buildup and abnormal absorption of nutrients in the small intestine

Learning Catalytics – Question #5 – Cystic Fibrosis Carrier Probability Calculation

• Your paternal grandfather’s sister died from cystic fibrosis. Your grandfather is not affected. What are the chances you are a carrier?
• $P(Aa) = P(A from mom) * P(a from dad)$
• $P(Aa) = (1) * ( frac{2}{3} * frac{1}{2} * frac{1}{2})$
• $P(Aa) = ( frac{1}{6})$

Gene Expression | Gene to Protein May 28th, 2025

Chapter 17 | Key Concepts

• Genes specify proteins via transcription and translation
• Transcription is the DNA-directed synthesis of RNA
• Eukaryotic cells modify RNA after transcription
• Translation is the RNA-directed synthesis of polypeptides
• Mutations in one or few nucleotides can affect protein structure and function

Overview: The Flow of Genetic Information

• Proteins are the link between genotype and phenotype
• The genome [DNA] fulfills two roles:
• Encodes protein-coding genes
• Regulates its own expression
• Gene expression: process by which DNA directs protein synthesis
• Includes two stages: transcription and translation

Basic Principles of Transcription and Translation

• Primary transcript: The initial RNA transcript from any gene prior to processing
• Central dogma: Cells are governed by a cellular chain of command: DNA -> transcription -> RNA -> translation -> protein

Codons: Triplets of Nucleotides

• Triplet code: a series of nonoverlapping, three-nucleotide “words”
• Complementary nonoverlapping three-nucleotide words of mRNA
• Translated into amino acids, forming a polypeptide

The Genetic Code

• Template strand: During transcription, one of two DNA strands serves as a template for ordering the sequence of complementary nucleotides in an RNA transcript
• The template strand is always the same strand for a given gene
• Codons: During translation, mRNA base triplets are read in the 5′→3′ direction
• Each codon specifies an amino acid placed at the corresponding position along the polypeptide

The Codon Table for mRNA

• All 64 codons were deciphered by the mid-1960s
• Of the 64 triplets, 61 code for amino acids; 3 triplets are “stop” signals to end translation
• Redundancy in codons

The Stages of Transcription

1. Initiation: RNA Polymerase binds to promoter on template strand
2. Elongation: Reads 3’ to 5’, unwinding DNA
3. Termination: Dissociates when it reaches stop signal [polyadenylation signal sequence in eukaryotes]

Initiation of Transcription

1. RNA Polymerase binds to promoter on template strand
2. Usually [TATA box] 25 nucleotides upstream from the start point

The Initiation of Transcription at a Eukaryotic Promoter

• Transcription initiation complex: Assembly of transcription factors and RNA polymerase II bound to a promoter
• TATA box: A promoter element crucial for forming the initiation complex in eukaryotes; 25 bases upstream
• Transcription Factors: Recognize TATA and bind to DNA; necessary
• RNA Pol II binds to template strand, reads 3’ to 5’

Elongation of the RNA Strand

• As RNA polymerase moves along DNA, it untwists the double helix, 10 to 20 bases at a time

Termination of Transcription

• In bacteria, the polymerase stops transcription at the end of terminator
• The mRNA can be translated without further modification
• In eukaryotes, RNA polymerase II transcribes a polyadenylation signal sequence [poly-A tail]
• The RNA transcript is released 10–35 nucleotides past this polyadenylation sequence

Completed RNA Transcript

• Difference between prokaryotes and eukaryotes
• In bacteria, the polymerase stops transcription at the end of terminator
• The mRNA can be translated without further modification

Eukaryotic Cells Modify mRNA After Transcription

• Primary transcripts or pre-mRNA RNA processing mRNA
• Enzymes in the nucleus of eukaryotes modify pre-mRNA during RNA processing before it is dispatched to cytoplasm
• Both ends of the primary transcript are usually altered
• Often, certain interior parts of the mRNA are also cut out, and the remaining parts are spliced together

RNA Processing: Alteration of mRNA Ends

• Each end of a pre-mRNA molecule is modified
• The 5′ end receives a modified nucleotide 5′ cap
• The 3′ end gets a poly-A tail

RNA Processing: RNA Splicing

• Most eukaryotic genes have long noncoding stretches of nucleotides that lie between coding regions
• These noncoding regions are called introns or intervening sequences
• Coding regions are called exons as they are expressed as amino acid sequences

RNA Processing: RNA Splicing

• RNA splicing removes introns and joins exons, creating an mRNA molecule with a continuous coding sequence

RNA terminology

• Introns – Intervening sequences that are taken out
• Exons – expressed sequences into protein when exit out of nucleus

The Roles of snRNAs and Spliceosomes in Pre-mRNA Splicing

• Small nuclear RNAs [snRNAs] recognize splice sites
• snRNAs are examples of ribozymes [RNA molecules that function as enzymes]
• The RNAs of the spliceosome also catalyze the splicing reaction

Why have Introns? Functional & Evolutionary Importance

• Some introns contain sequences that may regulate gene expression
• Genes can encode more than one polypeptide, depending on which segments are treated as exons during splicing
• This is called alternative RNA splicing

Alternative Splicing

• Consequently, the number of different proteins an organism can produce is much greater than its number of genes
• In humans, ~ 95% of genes with multiple exons exhibit alternate splicing
• Proteins often have modular architecture consisting of discrete regions called domains

Gene Expression | Translation

• Process by which mRNA is used for protein synthesis

Translation | Stages

• Initiation: Start codon AUG, Initiation factors, and translation initiation complex
• Elongation: 5’ to 3’ codon recognition, peptide bond formation, translocation
• Termination: Stop codon, release factor and hydrolysis, translation assembly dissociates

Structure of Transfer RNA [tRNA]

• “Translator” molecule
• A tRNA molecules consists of a single RNA strand ~80 nucleotides long
• Flattened into one plane to reveal its base pairing, a tRNA molecule looks like a cloverleaf
• tRNA molecules are not identical
• Each carries specific AA
• Each has an anticodon; pairs with complementary codon on mRNA

Aminoacyl-tRNA Synthetase

• Accurate translation requires two steps:
• Correct match between tRNA and amino acid, catalyzed by aminoacyl-tRNA synthetase
• Correct match between tRNA anticodon and mRNA codon

Ribosomes

• Facilitate specific coupling of tRNA anticodons with mRNA codons
• Two ribosomal subunits [large and small] are made of proteins and ribosomal RNA [rRNA]

Ribosomes | tRNA Binding sites

• A ribosome has three binding sites for tRNA: P site, A site, E site

Translation | Initiation

• Proteins called initiation factors bring in the large subunit that completes the translation initiation complex

Translation | Elongation

• Amino acids added to preceding AA at the C-terminus of the growing chain
• Three steps:
• Codon recognition
• Peptide bond formation
• Translocation

Translation | Termination

• Occurs when mRNA stop codon reaches the A site. No tRNA anticodon for stop codons
• Site accepts a protein called a Release factor that causes the addition of H2O instead of an amino acid
• This reaction releases the polypeptide, and the translation assembly disassociates

Post-Translation Modification & Trafficking

• Often translation is insufficient to make a functional protein & polypeptide chains are modified post-translation
• Amino acid side chains may be modified
• Macromolecules may be added (e.g., peptide + carbohydrate = glycoprotein)
• Proteins may be cleaved OR protein subunits may be joined
• Polypeptides produced may be sent to targeted areas in the cell

Translation | Targeting Proteins to the ER

• Signal-Recognition Particle [SRP] binds to the signal peptide and brings it and its ribosome to the ER for final modification

Polyribosomes

• Multiple ribosomes can translate a single mRNA simultaneously, forming a polyribosome, or polysome
• Enable cells to make many polypeptides very quickly
• Amplifies gene expression!

Gene Expression | Mutations

• One or few nucleotide change can lead to large changes in protein structure and function

Small-scale Mutations

• Small-scale Mutations in one/few nucleotides can affect mRNA sequence and protein structure and function
• Types of Mutations:
• Substitutions:
• Silent
• Nonsense
• Missense
• Frameshift or in/dels
• Insertion
• Deletions

Mutations | Silent Mutations

• Have no effect on amino acid produced by codon because of genetic code redundancy

Mutations | Nonsense Mutations

• Change an amino acid codon into stop codon, nearly always leading to nonfunctional protein

Mutation | Missense Mutations

• Still code for an amino acid, but not the correct amino acid

Mutations | Frameshift | Insertion

• An extra nucleotide inserted
• Leads to all subsequent codons and AA altered
• Can also lead to a nonsense [Stop codon] mutation

Mutations | Frameshift | Deletion

• A nucleotide is deleted/missing leading to all subsequent codons shifting
• Can also lead to a nonsense [Stop codon] mutation

Molecular Basis of Sickle Cell Anemia

• A single point mutation in DNA leads to altered mRNA and a change in the amino acid sequence of the protein, resulting in sickle cell hemoglobin.

What is a Gene?

• A gene can be defined as a region of DNA that can be expressed to produce a final functional product, either a polypeptide or an RNA molecule

Review: Transcription and Translation

• RNA
• DNA
• DNA
• TRANSCRIPTION
• CYTOPLASM
• mRNA
• TRANSLATION