BIMM 120_Midterm #1_Saier Milton

3 Laws of Biology

1. Biology Obeys Chemistry & Physics

-1st Law of Thermodynamics: Energy/matter cannot be created or destroyed, only transformed 

-2nd Law of Thermodynamics: Entropy increases in a closed system

-Cells are open systems that maintain order via metabolism by ↓ internal entropy, ↑ external entropy, and equilibrium = death.

2. All Life Is Membrane-Bound

-Life consists of membrane-encased cells.

-Cells grow and divide independently; viruses are not living.

-Life is genome-encoded, but early life required symbiosis due to incomplete genomes.

3. All Life Evolved

-All life shares a common ancestor

-Evidence: Universal genetic code

-Darwin’s natural selection acts on genotype & phenotype. Early evolution = cooperation. Later evolution = increasing competition as independence arose

Metagenomics:

-Environmental DNA → PCR → sequencing → genome assembly. Revealed unculturable organisms and expanded the tree of life (Castelle & Banfield, 2018).

Timeline of Life on Earth

-Bacteria → Archaea → Eukaryotes (evolved from Asgard archaea).

Lamarck vs Modern View

-Lamarck: Inherited traits acquired by use/disuse (incorrect).

-Modern biology: All biological information is genome-encoded.

-Bioinformatics & phylogeny best predict function and evolutionary relationships.

Transport Classification DataBase (TCDB):

Classifies transporter proteins by function and evolutionary history.

Nucleotides & Bonding

-Purines: 2 rings (A, G)

-Pyrimidines: 1 ring (U, T, C)

-C:G = 3 H-bonds (stronger); A:T / A:U = 2 H-bonds (weaker)

-Bond strength depends on geometry (linear > bent)

Codon Position Importance:

-P2 > P1 > P3

• P2: Determines amino acid chemistry

(a) P2 = A → hydrophilic P2 = T → hydrophobic

(b) P2 = T → hydrophobic

(c) P2 = C/G → semi-polar

• P1: Controls P3 importance

(a) P1 = A/T: P3 changes AA

(b) P1 = C/G: P3 is silent

• P3: Wobble position → often synonymous (no AA change)

Codon Redundancy:

Multiple codons per amino acid to protect against harmful mutations via synonymous changes.

Codons & Termination during Translation Rules

-Initiation codons: AUG > GUG > UUG/CUG → all read as fMet (Always Give Unconditional Cuddles)

-Initiation wobble = P1 → ribosome recognition.

-Stop codons: UAA > UAG > UGA

-Weaker H-bonds → easier polypeptide release.

-Highly expressed genes use more common codons at higher frequency for translation

mRNA–tRNA Asymmetric

-Pairing is direction-dependent (A:T ≠ T:A; C:G ≠ G:C).

-Stronger binding: tRNA purine : mRNA pyrimidine

Partial Microbes (CPR, DPANN, Asgard)

-Early microbial lineages with reduced genomes, metabolic incompleteness, cannot live independently, and rely on obligate symbiosis. Early evolution = cooperation. Later evolution = increasing competition as independence arose

CPR (Candidate Phyla Radiation) Bacteria:

Reduced genomes, lack biosynthetic pathways, and rely on host

DPANN Archaea:

Reduced genomes, attach to hosts, form biofilms, and show gene sharing.

Asgard Archaea:

Contains eukaryotic signature proteins (ESPs) that support eukaryote origin.

Isoprenoids & the “Lipid Divide”:

-Isoprenoids are essential metabolites.

-Lipid Divide: Archaea: MVA pathway; Bacteria: MEP pathway. Some CPR bacteria lack MEP, showing the divide is oversimplified and ancient.

Metabolic Handoffs:

One organism’s waste is another's substrate, enabling survival in nutrient-poor environments.

Cooperation & Competition (Saier, 2025)

-Early evolution: cooperation & metabolic integration.

-Later evolution: increased competition.

-Endosymbiosis formed mitochondria (proteobacteria) and plastids (cyanobacteria: ex = chloroplast).

Nanoarchaeum equitans:

Obligate symbiont of Ignicoccus with compact genome that redirects host metabolism. Model how early cooperation led to endosymbiosis and complex cells.

Ancient vs Modern Plagues

-Ancient plagues (Justinian, Black Death) spread via commerce (Silk Road).

-Modern plagues spread from close contact (e.g., wet markets) and air travel.

-Sanitation & ventilation reduce spread.

-Hippocrates separated medicine from superstition.

Black Death (Bubonic Plague)

-Caused by Yersinia pestis via fleas on rodents.

-Symptoms: buboes 

-30–60% mortality in Europe.

-Disease blamed on miasma (foul, polluted air) → believed solution: spice-filled masks.

-Treatment: Quarantine and burning houses.

Smallpox

-Caused by the Variola virus.

-Edward Jenner used cowpox for vaccination

(a) Variolation: smallpox exposure.

(b) Vaccination: weakened/related virus (safer).

H1N1 Flu

-Hemagglutinin (H): host cell entry.

-Neuraminidase (N): viral release.

-H & N constantly mutate → yearly flu vaccines.

Influenza

-RNA viruses A, B, C (identified in pigs by Richard Shope).

-Strain A causes most infections

-H and N mutate to evade the immune system.

(a) H1N1 (Swine/Spanish flu): most prevalent; vaccines exist.

(b) H5N1 (avian flu): high fatality rate; no immunity yet.

-mRNA vaccines provide best protection against flu

-Co-infection → recombination → ↑ pathogenicity.

Zoonotic

animal → human transmission

1918 Influenza (H1N1)

-Zoonotic: avian → pig → human.

-High mortality and altered WWI.

-Ages 25–44 most affected due to cytokine storm.

Transmissibility and Virulence:

-Evolution favors more infectious, less virulent/lethal strains.

-Disfigure host to maximize virulence

Virus Evolution

-Viruses mutate to less lethal strains. Evolution favors more infectious, less virulent strains

Flu Vaccine

-Based on circulating strains (USA uses Southern Hemisphere data).

~⅔ effective; excellent at preventing death.

Poliomyelitis

-Enters gut → bloodstream → CNS.

-Kills motor neurons → paralysis & muscle atrophy.

-Iron lung used for respiratory failure.

-Vaccines:

(a) Salk: inactivated (heat-killed) virus → no replication, safe immunity.

(b) Sabin: attenuated, oral vaccines → weakened virus, antigen recognition.

Measles

-Most infectious virus known.

-MMR vaccine is highly effective.

-High R₀ → outbreaks if unvaccinated.

-95% herd immunity required.

Thinking Like Bacteria

-Less host damage → better spread.

-Syphilis evolved milder symptoms.

-Cough-inducing toxins aid transmission.

COVID-19 (SARS-CoV-2)

-Zoonotic: bats → animals → humans.

-Spread via air travel.

-Spike (S) protein binds ACE-2 receptors for cell entry.

-Spike mutations allow vaccine escape and new waves.

Vaccine Hesitancy

-Driven by misinformation, mistrust, politics, access

-Scientific consensus: vaccines reduce severity and death.

Eating Animals & Viral Epidemics

>75% of emerging diseases are zoonotic.

-No plant virus causes human epidemics.

-Host–pathogen arms race: host adapts ↔ pathogen adapts.

Antigenic Drift vs Shift:

-Antigenic Drift: small, gradual mutations (e.g., H/N in influenza).

-Antigenic Shift: major reassortment between animal & human viruses → new surface proteins → pandemics.

SARS (Severe Acute Respiratory Syndrome)

-Linked to live animal markets.

-Horseshoe bats → animals → humans.

-Transmission via direct animal contact.

MERS (Middle East Respiratory Syndrome)

-Coronavirus related to SARS.

-Bats → camels → humans.

-Higher virulence and respiratory failure than SARS-CoV-2.

-Limited spread due to high lethality + camel geography.

Animal reservoir:

Species that harbors pathogens long-term and enable spillover (e.g., bats due to enhanced DNA repair mechanisms associated with high-energy flight).

Ebolavirus

-Reservoir: fruit bats

-Causes hemorrhagic fever and spread via bodily fluids, bush meat, human and animal contact

Marburg Virus

-Enveloped RNA filovirus causing hemorrhagic fever.

-Reservoir: fruit bats → primates & humans.

-Highly mutable → expanded host range → primate → human spillover.

HIV

-Zoonotic: SIV → humans (primates, Africa).

-Enveloped RNA lentivirus causing AIDS.

-Spread via blood, sexual contact, and bush meat.

-Retrovirus: RNA → DNA integration into host genome.

-High mutation rate due to error-prone replication.

-No cure or vaccine, but antivirals suppress replication, making HIV a chronic disease.

Avian Influenza Virus

-Influenza A from wild birds

-H5N1: massive poultry deaths; mutations enable human reservoirs.

-High mutation rate → requires surveillance & updated vaccines.

Swine Influenza Virus

-Pigs have avian + human receptors enabling co-infection → reassortment → novel (more virulent viruses).

-Pigs are “mixing bowls” (intermediate hosts).

-Source of H1N1.

Prion Diseases

-Caused normal proteins to misfold:

-Self-propagating chain reaction: Kuru (cannibalism) and BSE (Mad Cow Disease) → vCJD in humans.

-Peyer patches allow replication after oral exposure, enabling spread.