Bio 130 Unit Two

Prokaryote Reproduction

1. DNA replication begins in the center of the cell

2. Chromosomal DNA replicates

3. Daughter DNAs separate, cell begin to divide

4. Cytokinesis is complete, two new cells formed

Bacterial Reproduction

1. DNA copied and protein filaments attach

2. DNA copies are separated and ring of protein forms

3. Protein pulls it apart

4. Two different cells

Chromosomes

Humans have 23 pairs of chromosomes - organized by length (biggest (1) → smallest (22, then Y)) - one chromosome of each pair/type from each parent (23 total from each parent)

Mitosis

Purpose is growth, repair, reproduction - DNA is twisted and condensed to form condensed, replicated chromosomes with sister chromatids - this helps the DNA become tight and small bc it’s a lot easier to pull into a new cell - connected sister chromatids are one chromosome, but when its separated they’re two chromosomes - microtubules grab onto chromosomes at the kinetochores

1. Interphase

2. Prophase

3. Prometaphase

4. Metaphase

5. Anaphase

6. Telophase

7. Cytokinesis

Cell Cycle Phases

1. First gap (G₁)

2. DNA Synthesis (S)

3. Second Gap (G₂)

4. Mitosis (M)

Cell Cycle First Gap (G₁)

At G₁ checkpoint, mature cells do not pass (enter G₀ state of dormancy)

Pass G₁ checkpoint if:

• Cell size is adequate,

• Nutrients are sufficient,

• Social signals are present

• DNA is undamaged

If it doesn’t pass, apoptosis occurs (programmed cell death)

Cell Cycle DNA Synthesis

Doubles the DNA

Cell Cycle Second Gap (G₂)

G₂ checkpoint passed if:

• Chromosomes have replicated successfully

• DNA is undamaged

• Activated MPF (mitosis-promoting factor) is present

Cell Cycle Mitosis (M)

Mitosis checkpoint passed if:

• Chromosomes have attached to spindle apparatus

• Chromosomes have properly segregated and MPF is absent

Cancer

Uncontrolled cell division - cell cycle not regulated - benign means it grows in a certain location and malignant means it divides and spreads to other tissues/areas through the lymphatic vessels and/or blood vessels - metastatis is the process of a malignant cancer spreading somewhere new

Mitosis-Promoting Factor (MPF)

Protein dimer (two proteins linked together) of cyclin (regulatory protein) and cycline-dependent kinase or Cdk (catalyzes phosphorylation of other proteins to start M phase) - increasing MPF concentration hits threshold point which triggers mitosis

Chromatin

DNA complexed with histone proteins

Kinetochores

Structures on sister chromatids where microtubules attach

Interphase (mitosis)

G₁, S, and G₂ phases - DNA is more unbundled until chromosomal replication

Prophase (mitosis)

Chromosomes condense and spindle apparatus begins to form

Prometaphase (mitosis)

Nuclear envelope breaks down, microtubules contact kinetochores

Metaphase (mitosis)

Chromosomes complete migration to middle of cell - they’re lined up in the middle

Anaphase (mitosis)

Sister chromosomes separate into daughter chromosomes and are pulled apart

Telophase (mitosis)

Nuclear envelope reforms and chromosomes decondense

Cytokinesis (mitosis)

Cell division, cytoplasm divided

How do cancer treatments work

Chemotherapy uses chemicals like terpenoids (block microtubule formulation), anti-metabolites (fake purines and pyrimidines so DNA synthesis can’t occur), and taxol (stabilizes microtubules so they don’t grow) which bind to cancer cells and messes up their DNA so it won’t pass the checkpoints to divide (causes apoptosis) - Radiation damages DNA

Diplontic Life Cycle

Gametes are the only part/time in haploid stage - otherwise, its a diploid with two sets of chromosomes - ex. humans

Haplontic Life Cycle

Zygote is the only diploid stage - otherwise, its a haploid with one of each kind of chromosome - ex. bread mold

Alternation of Generations

50/50 split between haploid and diploid during its lifetime - ex. ferns

Meiosis One Phases

1. Interphase

2. Early Prophase I

3. Late Prophase I

4. Metaphase I

5. Anaphase I

6. Telophase and Cytokinesis

Early Prophase I (meiosis)

Chromosomes are bivalent (line up with each other so there’s four sister chromatids in a “row”)

Late Prophase I (meiosis)

Chiasma where the DNA swaps - recombination

Metaphase I (meiosis)

Chromosomes are lined up from side to side (instead of top to bottom in mitosis) and spindles attach

Anaphase I (meiosis)

Chromosomes pulled apart so there’s two sister chromatids on both sides

Meiosis Two Phases

1. Prophase II

2. Metaphase II

3. Anaphase II

4. Telophase II and Cytokinesis makes four gametes

Basically just mitosis

Paradox of Sex

Sexual reproduction is way slower (less offspring) so the payoff must be huge to pay this price - sexual reproduction produces variable offspring which is way more advantageous to survive and reproduce (bc of natural selection) - increased genetic variations from crossing over and independent assortment

Independent Assortment

During meiosis I, tetrads can line up two different ways before homolog separate - leads to increased genetic variations - the inheritance of one trait doesn’t affect the inheritance of another - only works when traits are on different chromosomes - evidence comes from dihybrid cross (9/16, 3/16, 3/16, 1/16)

Two mechanisms by which gametes become different from each other

1. Crossing Over

2. Independent Assortment

Nondisjunction

Tetrads don’t separate so some cells have three homologs (n+1) and others have one (n-1) - leads to aneuploidy like trisomy (ex. down syndrome) or missing chromosome (ex. turner syndrome)

Gregor Mendel

Bred peas to observe their variations in seed shape/color, flower color, pod shape, etc. - formed the foundation for genetics through particulate inheritance - he thought traits were discrete (no blending inheritance) and that peas have two versions (alleles) of each gene (no acquired characteristics) - Principle of Segregation - independent assortment

Principle of Segregation

Explained 3:1 ratio of phenotypes by reasoning that alleles separate randomly and can combine in different ways - each offspring receives one allele for each trait from each parent (punnett squares)

Test Cross

Cross homozygous recessive with individuals of an unknown genotype to determine their genotype based on the offspring produced

Reciprocal Cross

A cross in which the phenotypes of the male and female are reversed compared with a prior cross - Cross male of part A with female of part B and then female of part A with male of part B - If reciprocal crosses give identical results, the sex of the parent does not Influence transmission of the trait (like with Mendel’s peas)

Chromosomal Theory of Inheritance

Meiosis can explain both the principle of segregation and the principle of independent assortment

• Principle of Segregation: alleles separate in meiosis

• Principle of IA: chromosomes can line up in two different ways during meiosis I (metaphase I)

Synapsis

The close pairing of two homologous (matching) chromosomes that happens during prophase I of meiosis - mom sister chromatids and dad sister chromatids together - allows for crossing over to happen

Particulate Inheritance

Created by Mendel - traits are passed from parents to offspring through discrete units called genes (no mixing/blending)

Codominant

Two different alleles for a gene are both fully expressed at the same time in a heterozygous organism - ex. blood type AB

Overdominant

An individual with two different alleles (heterozygous) has a higher survival rate or better fitness than an individual with two identical alleles (homozygous) - ex. the hemoglobin alleles that cause sickle-cell anemia where having both dominant alleles mean you’re more prone to getting malaria and having both recessive alleles means you’re super anemic, so being heterozygous gives you a higher survival rate

Pleiotropy

A single gene influences multiple, distinct, and seemingly unrelated phenotypic traits - antagonistic pleiotropy explains aging (tradeoff between high fitness in your age and decreased fitness later)

Examples:

• Cystic fibrosis is a mutation in one gene that affects the lungs, pancreas, and sweat glands all at the same time

• p53 suppresses cancer but also suppresses stem cells

Epistasis

The expression of one gene is affected by another gene (modifier gene) - One gene masks, suppresses, or modifies the phenotype of a completely separate gene - ex. for dogs, expression of the E gene determines expression of B gene (with ee, no B or b is expressed at all)

Ploidy

The number of complete sets of chromosomes in a cell - ex. haploid, diploid, tetraploid, aneuploid

Transformation

The process where a cell takes up naked, external genetic material (DNA) from its environment and incorporates it into its own genome

Semiconservative Replication

The standard method of DNA replication in which a double-stranded molecule separates and each strand acts as a template to build a new complementary strand - the original parent DNA strands are separated and each one is used to code a new strand - so, the new strands contain half of the parent DNA strand (semiconservative)

DNA Polymerase

An enzyme that creates new DNA strands during DNA replication - “reads” the existing DNA to build a complementary match - builds from 5’ to 3’ - requires an RNA primer

Leading Strand vs. Lagging Strand

Leading strand is built continuously from 5’ to 3’ towards the replication fork - DNA polymerase moves smoothly, only one RNA primer needed - alternatively, the lagging strand is synthesized in short pieces away from the replication fork (5’ to 3’) - the short blocks of DNA made are called okazaki fragments - needs lots of RNA primers and DNA ligase has to stitch the okazaki fragments together

mRNA

Carries genetic instructions from the DNA in the cell’s nucleus to the cytoplasm for protein synthesis - created during transcription, leaves the nucleus during transport, and is translated in sets of three bases (codons) to assemble amino acids into a functional protein - for eukaryotes, it has a 5’ cap (altered guanine) on one end and a poly-A tail (string of adenine) on the other to prevent early breakdown

Introns

Non-coding intervening sequences that break up the coding region of a gene and are transcribed into pre-mRNA - these are removed by RNA splicing so that mature mRNA can form proteins - allows exons to be mixed and matched in different ways, creating multiple proteins - controls gene regulation and expression - interrupting sequences

Exons

The segments that stay in the mature messenger RNA (mRNA) and usually provide the code to build proteins - expressed sequences

Spliceosome

A large molecular machine in the nucleus that removes introns from pre-mRNA and joins exons together - made of both RNA and proteins

RNA Polymerase

Builds an RNA strand by following a DNA template during transcription - Builds RNA from 5’ to 3’ based on the genetic instructions of the DNA sequence

• RNA Polymerase I makes most rRNA (ribosomal RNA that positions and checks mRNA)

• RNA Polymerase II makes mRNA (messenger RNA that encodes proteins)

• RNA Polymerase III makes tRNA (transfer RNA that does the decoding)

Terminator

A specific section of nucleic acid sequence in DNA that marks the end of a gene or operon during transcription - ends transcription, releases RNA

Promoter

A specific region of DNA located upstream of a gene that acts as a binding site to initiate transcription - attachment site for RNA polymerase, defines where transcription begins - ex. TATA Box

Transcription Factors

Specialized proteins that bind to specific DNA sequences to turn genes "on" or "off" by regulating when and how much DNA is copied into RNA - can boost DNA transcription by recruiting RNA polymerase, repress DNA transcription by blocking RNA polymerase, and guide development

Ribozyme

An RNA molecule that can act as an enzyme to catalyze specific biochemical reactions - RNA can catalyze reactions!

rRNA

Ribosomal RNA - joins with proteins to form the ribosomes, which build proteins in all living cells - builds ribosomes, catalyzes bonds, and aligns mRNA in translation

Codon

A sequence of three consecutive nucleotides in a DNA or RNA molecule that codes for a specific amino acid or signals the start or end of protein synthesis

Anticodon

A sequence of three nucleotide bases on a tRNA molecule that bonds with a complementary codon on a mRNA strand during protein synthesis - ex. AAG anticodon bonds with UUC mRNA codon

Reading Frame

A specific way of dividing a nucleotide sequence into consecutive, non-overlapping triplets (codons) that code for amino acids - chooses the possible ways to read the nucleotide sequence - ex. UAGUAGUAG could be read as codons of UAG, codons of AGU, or codons of GUA

tRNA

Transfer RNA - reads the triplet genetic code on the mRNA molecule inside the ribosome, carries the corresponding amino acid to the ribosome to build the polypeptide chain (with help from aminoacyl-tRNA synthase)

Aminoacyl-tRNA synthase

An enzyme that attaches a specific amino acid to its corresponding transfer RNA (tRNA) molecule

Wobble

Explains how a single transfer RNA (tRNA) molecule can recognize and bind to multiple different mRNA codons during protein translation - The first two nucleotides of the mRNA codon form strict, conventional base pairs with the last two nucleotides of the tRNA anticodon - The third codon nucleotide and the first anticodon nucleotide have "wobble," allowing non-standard bonding - Because of this wobble, cells do not need a unique tRNA for every single one of the 61 codons - ex. G can pair with C or U, U can pair with A or G, or I (a modified base) can pair with A, U, or C

Post-Translational Modifications (PTMs)

Covalent chemical changes that alter a protein's properties, activity, and lifespan after it is translated from mRNA - helps with protein folding and stability, cellular localization, and activity control (turns enzymes on/off)

Examples:

• Phosphorylation - adds phosphate to act as molecular switch

• Acetylation - adds acetyl group for histone regulation and gene expression

Mutation and how it happens

A permanent change in the DNA sequence in an organism or virus - caused by replication errors or mutagens

• Substitution - Swapping one DNA base for another

• Insertion - Adding extra base pairs

• Deletion - losing some base pairs

• Frameshift - insertions/deletions can mess up the codons, leading to nonfunctional proteins

Mutagens

Changes the genetic material (usually DNA) of an organism and increases the frequency of mutations above normal levels

• Physical: UV light, X-rays, gamma rays

• Chemical: base analogs and other things

• Biological: viruses, bacteria

Point Mutation

A mutation where a single nucleotide is replaced, inserted, or deleted - can be silent (codes for same amino acid), missense (changes the code to code for a different amino acid), or nonsense (changes the codon into a premature stop signal)

Missense Mutation

Changes the DNA codon to code for a different amino acid

Nonsense Mutation

Changes the DNA codon into a stop codon, ending translation early

Gene Duplication

A type of mutation where an extra copy of a DNA segment, ranging from a single gene to an entire chromosome or genome, is produced

Inversion

A structural mutation where a segment of a chromosome breaks off, flips 180 degrees, and reattaches in reverse order

Ribonucleases

Enzymes that break down RNA into smaller components or single nucleotides - good for RNA processing (maturing mRNA or tRNA into functional form), breaking down RNA, fighting viruses, etc.

Gene Expression

Which/How are the genes in our DNA expressed? - Our cells can use different on/off switches to express certain genes and not others, leading to the specialization of cells - for example, transcription factors (activators and repressors) can start/stop transcription

Transcriptional Control

The process of regulating the rate at which RNA polymerase transcribes a gene into RNA - promoters allow RNA polymerase and transcription factors to bind - transcription factors like activators and repressors can turn genes “on” and “off”

Translational Control

The regulation of how much protein is made from existing mRNA inside a cell

• Initiation: deciding whether the ribosome can attach to the mRNA to begin reading it

• Elongation and Termination: cells can also slow down, pause, or stop the ribosome while it is moving down the message

Molecular Chaperones

Specialized proteins that assist in the proper folding, stabilization, assembly, and transport of other proteins within the cell

Polygenic Inheritance

Phenotypes can be the product of 2+ genes, vary in degree - expression approximates a bell curve - complicated by interplay between genes and the environment - ex. human skin color, height, body mass, etc.

Genetic Recombination

Linked genes segregate together except when crossing over and genetic recombination have occurred in meiosis I - physical distance between genes determine the frequency of recombination (more recombination = further away on the chromosome and vice versa) - probability of recombination can be used to map the location of genes on a chromosome

Incomplete Dominance

Heterozygous has an intermediate phenotype (ex. one white allele and one red allele is expressed as a pink phenotype)

Chromatin

DNA wraps around spool-like protein complexes called histones, forming structures called nucleosomes - these fold tightly together to form chromatin fibers, which condense even further during cell division to become visible chromosomes - chromatin can be loosely packed so it can be transcribed or tightly packed where the genes are inactive/silent (not expressed)

Histones

Spool-like protein complexes that DNA wraps around to form nucleosomes, which then fold to form chromatin - condenses DNA to fit in the nucleus and form chromosomes

Enhancer

A short region of DNA that binds proteins called activators (transcription factors) to increase the transcription of a gene - these help RNA polymerase work much more efficiently - can be located thousands of base pairs away, requiring the DNA to loop around so the enhancer can get close to the promoter

Silencer

A specific, non-coding DNA sequence that binds repressor proteins (transcription factors) to reduce or prevent the transcription of a target gene - binding of the repressor proteins prevents RNA polymerase from binding or running smoothly - can also work to tighten chromatin so genes can’t be accessed

Restriction Enzymes

Bacterial proteins that act as "molecular scissors" to cut double-stranded DNA at specific nucleotide sequences - destroy foreign DNA like viruses

Polymerase Chain Reaction

Biology technique used to make TONS of copies of a DNA sequence in a lab - denatures the DNA so it splits into single strands, uses primers so DNA polymerase can bind and quickly form new strands

Dideoxynucleotides

Modified nucleotide building blocks that lack a hydroxyl group (–OH) at the 3' carbon of their ribose sugar - terminates a DNA chain because more bases can’t be added - used by Sanger to sequence DNA

Open Reading Frame

A continuous stretch of DNA or RNA nucleotides that begins with a start codon and runs to a stop codon without any intervening terminators - this means it can be translated into a protein

Central Dogma of Biology

DNA → RNA → Protein