BIMM 120 - Midterm 1 (Saier)

second law of thermodynamics

entropy in a closed system always increases, ie. heat from a cold body won’t spontaneously go to a warmer body

1st law of biology

• all living organisms obey the laws of thermodynamics

• cells exist in open systems to exchange materials (metabolism)

• there’s genetic variation from sexual reproduction and evolutionary divergence

1st law of biology - 1st collary

• life requires creation of temporary order, seemingly contradicting 2nd law of thermodynamics

• resource utilization decreases entropy in living things but increase entropy of the world

1st law of biology - 2nd collary

• an organism at equilibrium = dead

• change must be occuring, ie. breakdown, build up, reproduction

2nd law of biology

• all living organisms have membrane-encased cells

• creates physical separation for material exchange

• viruses and plasmids aren’t alive because can’t reproduce on their own

2nd law of biology - 1st collary

• cell is the only structure that can fully grow and divide on its own

2nd law of biology - 2nd collary

• life and sexual reproduction is programed by genetic instructions

3rd law of biology

• all living things arose through evolution and are subject to the laws of natural selection

• all life is related

• there are programmed genetic similarities and differences

• natural selection occurs at both phenotypic and genotypic levels

3rd law of biology

3rd law of biology - 1st collary

• all living things contain homologous macromolecules (DNA, RNA, proteins) that came from a common ancestor

• homology - relatedness, or descent from a common ancestor, but says nothing about similarity

• analogy - similarity without homology, ie. convergent evolution

3rd law of biology - 2nd collary

• the genetic code is universal

why do RNA viruses evolve faster than DNA viruses?

• RNA = less stable than DNA

• DNA viruses can access host proofreading mechanisms which are generally more robust

many animal pathogens infect humans. what type of virus hasn’t caused an epidemic?

plant virus, are different enough

what’s “arms race”?

• the immune system learns from pathogens and pathogens learn from them

• viruses change their genomes leading to adaptations and eventual barrier jumping

how many emerging infectious diseases are zoonotic?

75%

Middle East Respiratory Syndrome (2012) (MERS)

• originated from bats —> suspect intermediate host were camels —> humans

• deadly but transmission was semi limited, wasn’t good at human to human spread

SARS-CoV-2 (2019-?)

• severe acute respiratory syndrome coronavirus-2

• is a positive-sense single-stranded RNA virus

• viral Spike (S) protein binds to ACE2 cell surface receptors of host to infect them

• S protein often changes when host changes and can change to increase host range

• bat reservoir —> suspect pangolins intermediate —> humans

• very good at jumping species

SARS-CoV-1

• common transmission: bats —> palm civets/raccoons —> humans

Ebola Virus (Zaire)

• is a negative single-stranded RNA virus

• fruit bats = reservoir

• vector was likely consuming/touching dead primates/bushmeat

• highly transmissible, causes deadly hemorrhagic fever virus

• fun fact: don’t affect dogs greatly

+ssRNA vs -ssRNA

+ssRNA = recognizable and can directly be translated into proteins by host cell ribosomes

-ssRNA = complementary to mRNA, needs to be transcribed into +ssRNA by RNA polymerases first before can be translated into proteins

bushmeat

meat from hunting wild animals (vs domesticated farm animals)

marburg virus

• similar to Ebola, causes hemorrhagic fever virus, with 25-90% lethality

• is -ssRNA and an enveloped RNA filovirus

• contract via direct contact with/ingestion of bushmeat (ie. bats/green monkeys)

• has a fast mutation rate because has very bad proofreading machinery (similar to Ebola)

• can bind to different surface receptors leading to wide host range

Human Immunodeficiency Virus (HIV-1&2)

• becomes AIDS (acquired immunodeficiency syndrome)

• technically a RNA virus but integrates into DNA genome via retrovirus

• is a RNA enveloped lentivirus

• has very high mutation rate due to retrovirus mechanism that uses reverse transcriptase which is faulty

• originated from cross species transmission of Simian Immunodeficiency virus (SIV), consumption/contact with dead primates

general influenza viruses

• are -ssRNA

• very fast evolution because multiple viral chromosomes, allowing recombination when infecting the same cell

avian influenze virus (AIV/bird flu)

• aka H5N1/influenza A virus, most pathogenic to humans

• hemagglutinin (H) = viral surface glycoprotein that binds to host receptor for entry

• neuraminidases (N) = cleaves sialic acid for viral exit

• mostly infects aquatic birds, has a high fatality rate (36-60%)

• structural genes for surface proteins mutate really fast, needing new vaccines yearly

swine influenza virus

• aka H1N1

• pigs have 2 kinds of receptors: 1 targeted by bird viruses and 1 targeted by human viruses, allowing pigs to swap genetic material and make more virulent strains

• considered “mixing bowls” of influenza

prion diseases

• aka transmissible spongiform encephalopathies (TSEs)

• caused by misfolded proteins, aggregates by causing other normal proteins to fold incorrectly

• bovine spongiform encephalopathy (BSE) - chronic degenerative disease causing the brain to form “sponges” in cows

• BSE —> human variant of BSV —> mutated into Creutzfeldt-Jakob disease (vCJD aka Mad Cow Disease)

• Scrapies = sheep variant

prion disease - peyer patches

where major prion proteins can be found, is the entire intestine of cows

what are the most common pathogens for foodborne illnesses?

bacteria, viruses, prions, protozoans

is Alzheimer’s Disease (AD) and Parkinson’s prion diseases?

No, just act like prion disease but aren’t from contaminated food

bacterial food poisoning - general

• not caused by single agent (bacteria, viruses, parasites, prions)

• main symptom (but not universal) = gastroenteritis = stomach flu = persisting diarrhea

• not everyone is susceptible to food poisoning, increased risks = age, pregnancy, compromise immune systems

• each cause may have different symptoms, most common being loss of fluids

bacterial food poisoning - gram (-) bacteria specific

• gram (-) proteobacteria = most common type (ie. E. Coli, Shigella, Salmonella, Vibrio, Campylobacter)

• salmonella and s. typhi causes typhoid fever

broad specificity pathogens

ability to bind to many host receptors because have adhesive fimbriae on bacteria surfaces that grab onto particular glycoproteins and glycolipids on host cell surfaces (ie. salmonella)

bacterial food poisoning - gram (+) bacteria specific

• ie. listeria in deli meats and unpasteurized milk

• ie. staphylococcus aureus in meat and eggs, can cause fever, chills, pneumonia, bacteremia, skin ulcers

viral food poisoning

• much less common because don’t replicate in food and are hard to replicate in cell cultures making detection hard

• most costly to detect and hardest to treat

  • don’t have good antiviral agents

virus recombination

ability of 2 related viruses to mix their genetic material creating more virulent mutants when in the same host

rotaviruses

• type of viral food poisoning

• is the primary cause of gastroenteritis in young children (<5 y/o then acquire resistance to more viruses)

noroviruses

• most common type of viral food poisoning

• a problem especially on cruise ships

  • common in oysters and seafood

why are bats often the original hosts for infectious disease?

• their immune systems allow for viruses to replicate quickly and aren’t virulent to them

• bats coexist with the viruses

• aren’t actually infected, just carriers

• live quite long and flying enables virus to spread easier

prion disease pathology

• cellular protein PrP^C with correct alpha folding misfolds into PrP^Sc with incorrect beta folding

• more recent discovery —> least understood and least amount of treatments

Alzheimer’s disease pathology

• caused by incorrect folding of Tau proteins and alpha-synuclein

• from aggregate Tau proteins that cause neurofibrillary tangles

• cells constitutively secrete tau at low levels under normal physiological conditions but pathway isn’t fully understood

protozoan food poisoning + “beaver fever”

• rare in developed countries

• most common = toxoplasma, cryptosporidium and giardia

• “beaver fever” - aka Giardia lamblia, is a pathogen found in mountain stream water

antigenic drift

small, gradual mutations leading to adaptations in viruses

antigenic shift

sudden, major genetic changes, ie. combination/exchange of genetic components from different viruses within a host

SARS

• severe acute respiratory syndrome

• replicase, RNA-dependent RNA polymerase is bad at proofreading leading to more rapid antigenic drift

• coronavirus replication machinery promotes viral recombination

1918 Spanish Flu epidemic

• aka H1N1/swine flue

• likely has an avian origin but has a massive host range

• a major transmission system = birds-pigs-humans crossover because pigs are viral mixing bowls for viral recombination

what strain of the flu are humans not immune to?

H5N1, obtained from cattle, currently not human-to-human transmissible

viruses in non-human primates (NHP)

• NHP = susceptible to human viruses and viruses circulate between them (ie. HIV and Zika)

• bats, primates, and rodents have higher proportion of zoonotic diseases

bovine spongiform encephalopathy (BSE)

• aka Mad Cow Disease

  • causes spongy degeneration of the brain and spinal cord

• caused by recycling sheep and cattle parts not used for human consumption to feed other cattle

• spread was stopped by banning certain animal parts from entering food chain

Kuru

passed between people who practiced cannibalism as a funeral tradition, is another prion disease but mostly irradicated now

what are the positions in an mRNA codon?

P1, P2, P3, P = position

what are the amounts of variation in each mRNA codon position?

• P1 = medium amount of variation

• P2 = least amount of variation of GC content

• P3 = largest amount of variation

what are each of the mRNA codon positions important for?

• P1 = important for the specific amino acid

• P2 = most important for determining the type of amino acid based on the codon

• P3 = wobble position, P2 determines its importance and even then, it only matters whether the position is a purine/pyrimidine

pyrimidine bases

C, U, T - “cut a pyramid”, have 1 aromatic ring

purine bases

A, G - “pure as gold”, have 2 aromatic rings

what’s the “negative selection principle”?

what is least important changes the most

what’s the new codon wheel Prof. Saier proposed?

• alternate wheel is based on P2

• contains 4 quadrants with T/U = hydrophobic, A = hydrophilic, and C or G = semi-polar

if 2 amino acids are related, what can be inferred about their codons?

• related amino acids have related codons

• similar amino acids will likely only vary in 1 position

wobble base pairing

• describes P3 where it allows specific alternate base pairing

• 1 amino acid can be coded by multiple different codons that differ on P3

What’s the wobble position in start codons?

P1 = wobble position for the start codons fMet (in bacteria) and Met (in eukaryotes and archaea)

H-bond differences between C+G and A+U

C+G has 3 H-bonds, A+U has 2 H-bonds

bond strength differences between tRNA and mRNA

tRNA and mRNA bonds are stronger when the tRNA is a purine and the mRNA is a pyrimidine

common nonsense (stop) codons

• all have U in P1 followed by 2 purines in P2 and P3

• UAA = “ochre",” most common stop codon, has the lowest possible H-bonds compared to all other stop codons making it stop easier

• UAA has 6 H-bonds total because U+A each have 2

primordial soup

• theory that life originated from soup of organic molecules

• such conditions can also give rise to nucleic acids, lipids, etc

frozen genetic code argument

genetic code = mostly universal, code was set in stone and optimized so mutations are deleterious, possible that universal code facilitates horizontal gene transfer

benefit of redundancy

with multiple codons coding for the same AA, the chance of a single nucleotide polymorphism (SNP) changing AA identity and causing problems is decreased

key finding regarding the relationship of eukaryotes and Asgard archaea

eukaryotes branched off from Asgard archaea or a very close relative

what is the mode of association between microbes especially for CPR bacteria and DPANN archaea?

episymbiosis, is understudied

what’s the importance of genome-resolved metagenomics?

genome-resolved metagenomics approaches allow study of metabolic pathways spanning different species in a community, “no cell is an island”

where was Asgard Archaea found?

sea floor sediments near hydrothermal vents

what’s the evidence supporting the relationship between eukaryotes and Asgard?

• Asgard genomes encode typically eukaryotic systems, suggesting Eukaryotes should be placed in Archaea

• ie. MVA lipid synthesis pathway, membrane remodeling/trafficking systems, cyotoskeletal proteins, ubiquitin, vesicle formation systems via actin, GTPases, and ESCRT

what is CPR and DPANN?

• CPR = candidate phyla radiation, nanobacteria, describes a collection of bacterial lineages

• DPANN = group of archaea

• both groups mostly consist of symbionts and episymbionts

episymbiont

a symbiont that lives on the surface of another organism for survival, not all symbionts are episymbionts (symbionts are a broad term, episymbiont is specific)

radiation

increase in taxonomic diversity that is caused by increased rates of speciation

what’s the new method to culture really small things like CPR and DPANN archaea?

classify based on metabolic insights by using metagenomics

what is the date regarding environments?

• many subsurface (under the Earth’s surface) environments = anaerobic, creating lineages that diverged early from primitive life forms

• low concentrations of nutrients so ensure nutrient retention using complex interdependencies, make them slow growing

characteristic of CPR bacteria

consistently have small genomes and cell sizes so most have a symbiotic lifestyle

DPANN archaea

• found in extreme environments (ie. heat, salinity, acidity)

• have small genomes, small cell sizes, and limited metabolic activities

• can’t make nucleotides, AAs, and lipids

• rely on other microbes to meet needs, seem to have genetic material to live independently but don’t use it

• can form biofilms and grow autotrophically

DPANN archaea - hami

unique surface attaching grappling hooks on their outer membrane

non-CPR bacteria in biogeochemical cycles

• were found and isolated in aquifer sediments (ie. Zixibacteria)

• capable of redox reactions and can mix aerobic and anaerobic pathways, allowing metabolic versatility and ability to survive in changing conditions

• metabolic abilities suggest fermentation, not photosynthesis, suggesting aerobic respiration came after photosynthetic machinery

• seem to exist in human microbiome because of detected cyanobacteria in human fecal matter

• lineage can be explored further through secondary metabolites

CPR bacteria vs DPANN archaea

• CPR have slightly different genetic codes (UGA codes for Gly instead of stop)

• CPR has unusual ribosome compositions, missing some universal “essential” ribosomal proteins

• exists metabolic variation between CPR and DPANN

• both radiations have common limited metabolic capacities, have shared gaps but gaps aren’t shared well with non-CPR symbiotes

• see bacterial genes in some DPANN archaea

what are CPR and DPANN episymbionts with?

• mostly symbionts with larger bacteria and archaea, can be associated with eukaryotic hosts though

• associate via surface of cells, cell-to-cell contact

• CPR cell surfaces have pili-like structures, imaged with Cryo TEM

• symbionts can supply what they can’t make themselves

what was proposed about Asgard archaea and its evolutionary relationship with eukaryotes?

• proposed that these archaea share a relatively close evolutionary relationship with eukaryotes and saw fusion of bacterial and archaea cells

• many archaea genes are considered Eukaryotic signature proteins

• suggest Asgard archaea = important precursors of early eukaryotic cells

what’s the “lipid divide”?

refers to the distinction between bacteria and archaea where the distribution of the MVA and MEP pathways in both domains reopens the question of their evolutionary origin

isoprenoids

essential metabolites in all living organisms in all domains of life

what are archaea and bacteria membranes made of?

isoprenoid-based lipids

• archaea use the MVA (mevalonate) pathway to make the isoprenoid-based lipid precursors

• bacteria use a nonhomologous MEP (methylerythritol) pathway to make the precursors

MVA vs MEP pathways in archaea vs bacteria

• few bacteria (mostly gram+) have MVA, ones that do predate the bacteria without MVA

• some CPR bacteria have MVA instead of MEP

• MEP pathway isn’t reported in archaea (except in Woesearchaeota)

• MVA was likely lost in most bacteria by horizontal gene transfer (?)

what’s the meaning of “metabolic handcuffs”?

means there’s extensive interconnection between metabolism of coexisting members and everything is made, consumed, and digested

4 main explanations to how CPR bacteria diverged from archaea - rapid evolution

reduced genomes tend to increase evolution rates in other symbiotes

4 main explanations to how CPR bacteria diverged from archaea - early divergence

possible that not enough is known about the missing links, many are anaerobes diverging before the Great Oxidation Event

4 main explanations to how CPR bacteria diverged from archaea - convergent evolution

similar habitats/lifestyles led to similar traits, this was mostly ruled out by nonoverlap with non-CPR genome-reduced symbionts like Buchnera

4 main explanations to how CPR bacteria diverged from archaea - horizontal gene transfer

“borrow” systems from other lineages, weak explanation for commonly retained pathways

what affects autism spectrum disorder (ASD)?

is highly multi-factorial, affected by genetics and environment, exists a connection between ASD and gastrointestinal (GI) issues

gut microbiota - general

• microbiome strengthens intestinal barrier integrity

• microbiota development starts at birth, stabilizes at about 3 y/o

• microbiota and CNS metabolism can directly/indirectly affect homeostasis

• growing evidence that dysbiosis (gut imbalance) can cause several diseases/disorders like ASD

metabolism in the microbiota

• microbiota produces many metabolites, ie. short chain fatty acids (SCFAs) which can act on the CNS through the microbiota-gut-brain-axis

• serotonin, tryptophan, etc levels can affect microbiome state

• tryptophan can be converted into a metabolite that generates neurotoxic products depending on microbiome changes

what is the ANS, ENS, and HPA, and how do they communicate?

• ANS = autonomic nervous system

• ENS = enteric nervous system

• HPA = hypothalmic-pituitary-adrenal axis

• communicate with each other via the vagus nerve to mediate gut-brain connection

• vagus nerve signals can be affected by the microbiota, changing host physiology and behavior

affects of metabolites from the microbiota on neurotransmitters (NTs)

metabolites from the microbiota cross the blood brain barrier (BBB) to change NT levels

maternal microbiota

• maternal gut microbiota modulates growth and fetal brain development

• birth method can significantly affect microbiome diversity via vertical transmission of microbiomes (c-section children have increased neurodevelopmental issues)

epigenetics

involves the epigenome which combines genetic and environmental influences to affect neurodevelopment

epigenetics’ role in microbiota and ASD

• changes acetylation and deacetylation patterns

• deacetylation causes chromatin condensation leading to gene inhibition

• histone deacetylases (HDACs) = targets of microbiota-derived metabolites

• ASD postmortem brain samples show abnormal mRNA alternative splicing

how does maternal gut microbiota influence the BBB?

maternal gut microbiota upregulates expression of tight junction proteins, decreasing permeability