Exam: Cycle 1

Viruses, Viroids, and Prions

1. Understanding viruses is important bc it can help us deal with virus outbreaks and tracking global migration to improve quality of life and prevent illnesses
2. Viruses aren’t always bad; we can use viruses’ properties for our own purposes (e.g. gene therapy)
3. Viruses aren’t considered to be living organisms because they lack many of the properties of life, and are infectious biological particles
4. Can’t reproduce on their own
5. No metabolic system to provide energy
6. Structure of virus is bare minimum to transmit genome: 1+ nucleic acid molecules, surrounded by a protein capsid, may have an envelope surrounding it
7. Can evolve, but isn’t a cell: no cytoplasm with plasma membrane (all other known living things do)
8. Viral genome: can be RNA or DNA, single or double stranded, a few to a hundred genes
9. Genes encode coat proteins, envelope proteins (if it’s an enveloped virus), regulation of transcription, may have virus-specific enzymes for replication
10. Two basic structural forms:
11. Helical: capsid proteins in a rod-like spiral around genome, often infects plants
12. Polyhedral: capsid proteins form triangular units that form a polyhedron, may have protein spikes (for cell recognition) from vertices
13. Bacteriophage is a complex polyhedral virus
14. Both helicals and polyhedrals can be enveloped in a membrane made from host’s membrane 
15. In enveloped viruses, proteins synthesized from viral genome in host cell are transported and embedded in membrane before leaving the cell (for cell recognition)
16. Classified into order, family, family, genera, species
17. Based on size, structure, genome structure (RNA or DNA, single or double stranded), how nucleic acid is replicated
18. We classified >4000 viruses into >80 families (21 include viruses causing human disease)
19. Family names end in -viridae, named after disease/place discovered/structure (e.g. Coronaviridae for crown of protein spikes on capsid)
20. Every living organism is prob permanently infected by 1+ kinds of viruses
21. Usually infects a single or a few closely related species, and possibly only one organ system/tissue
22. Some can infect unrelated species naturally or after mutating

1. May be deadly, bothersome, or helpful (can protect against other viruses’ replication)
2. Ex: bacteria don’t take over the planet bc of bacteriophages (phagein = eat)
3. Vital in ecosystems: affect nutrient cycling through effects on prokaryotic organisms (kills them to release nutrients), also keeps their photosynthesis going (has genes for a protein in photosystem II that needs to be replaced often: ‘selfish’ bc it’s to make sure the virus can reproduce but net result is good)
4. Viruses move randomly until they contact the surface of a host cell, virus/viral genome enters host cell, viral genes are expressed, viral genome reproduced, progeny viruses assembled, virions releases (often ruptures host cell)
5. Viruses infecting animal cells:
6. Genome and viral coat enter (envelope doesn’t enter) cell by endocytosis 
7. If no envelope, binds by recognition proteins to the plasma membrane. If envelope, the envelope fuses with cell membrane
8. Genome usually directs synthesis of additional viral particles the same as bacterial viruses
9. Regulated phage gene expression produces proteins and enzymes for phage → Phage DNA replicated in host cell by a phage encoded DNA polymerase → Viral units synthesized → Assembly → Phage directs synthesis of a lysozyme which ruptures the cell wall and releases 100+ progeny phages
10. Sometimes, replication is complex (e.g. HIV)
11. Has 2 copies of RNA and reverse transcriptase in the capsid → transcriptase makes a complementary DNA strand from viral RNA → second DNA strand made from first → DNA integrates into host cell as a provirus → transcribed and translated to make new virus parts → released
12. Most asymptomatic bc causing disease has no benefit to virus
13. But some cause issues: massive cell death, cell contents are released (and inflammation occurs, e.g. influenza), alters gene function (e.g. cancer)
14. May have a latent phase (e.g. herpes) and then act up in a period of stress
15. No fossil record of viruses (too small), but there are remains of viruses in the DNA of things it infected such as us
16. We think that viruses have been around as long as life has (bc it can infect all life), and evolved alongside/before earliest cells
17. Paleovirology based on genomics (of hosts)
18. DNA of virus can become integrated in DNA of host, can stay there indefinitely if doesn’t affect it, and if in gametes, can be passed down (and preserved p well, bc DNA’s mutation rate is relatively v low)
19. If bits are found in several animals, they must have a common ancestor, so virus is at least as old as the ancestor
20. E.g. circoviruses (dog stomach issues) found to be >68 MYO (found in dogs, cats, pandas)
21. Oldest: bracoviruses (in wasps) could be as old as insects, in the Carboniferous Period 310 MYA
22. Mammal gene CGIN1 seems to be from a retrovirus from 125-180 MYA
23. 8% of human genome includes sequences from viruses
24. Virus-first model: since they’re simpler, they evolved first
25. Escape hypothesis: viruses evolved after cells did, from DNA that escaped
26. Regressive model: based on discovery of giant viruses (e.g. mimicking microbe Mimivirus) that affect amoeba and can make protein
27. Life: reproduce, make energy for itself, maintain a stable environment within its cells, can evolve, etc
28. Viruses not alive bc: can’t reproduce by themselves, no energy metabolism, can’t respond to stimuli

Evolution In Action: HIV

1. HIV part of our population since 1981, was considered as a death sentence (causes AIDS, no treatment so immune system is weakened)
2. Until 1995, rate of new HIV infections increased and then started decreasing
3. Deaths from HIV peaked in 2005 and rate of death went down (bc treatment is better now)
4. Stats
5. In 2019: 38M ppl living with HIV, 1.7M newly infected, 770K died from related illnesses
6. Since 1981: 77.5M infected, 32.7M died
7. AIDS-related mortality decreased by 39% since 2010
8. Most ppl in Africa, then Asia + Pacific, then Europe and North America
9. Zoonotic disease: 75% of new infectious diseases, have ‘spilled over’ from other species (usually closely related), usually more harmful in new host than original reservoir species
10.  HIV: single stranded RNA virus called a retrovirus
11. Retrovirus: subset of viruses, single-stranded RNA has genetic material
12. SIV (Simian [primates] immunodeficiency virus): long history of infecting nonhuman primates, has spilled over to humans several times and those are called HIV
13. HIV’s RNA undergoes reverse transcription to synthesize a DNA strand which is integrated into into our genome using integrase, and then new virions can be made
14. Mutations (mistakes) may occur during the reverse transcriptase’s activity
15. AZT: first drug to treat HIV; a nucleoside analog (almost like thymine, but an OH on the 3-sugar is a N3)
16. When a thymidine is needed, the reverse transcriptase may take the AZT-triphosphate and then the rest of the strand can’t form 
17. AZT worked for a while, but after just a few months HIV was resistant to it
18. A mutation of just two bases in the reverse transcriptase gene (POL gene) on the HIV genome allowed a proof-reading ability so it could remove the AZT
19. Evolution of AZT resistance: random mistakes in copying the HIV genome results in mutations (may or may not give resistance to AZT) in progeny viruses in a person, AZT kills off the viruses that aren’t resistant, so the ones that are left are drug-resistant
20. High error rate for reverse transcriptase → variation in viral population’s ability to proof-read
21. Using antivirals provides an advantage to drug-resistant variants: mutations are always occurring randomly and the environment helps determine which variants can reproduce and pass on their genes, resulting in the viral population changing over time
22. Variation + heritability + non-random survival = evolution (by natural selection)
23. HIV is no longer a fatal disease; can live a pretty long life
24. Treatment is using many drugs that attack life cycle at diff points: resistance to many drugs is way less likely
25. Hard to make a vaccine bc high mutation rate and so many variants (e.g. ones that change the structure of the virus so it can evade the immune system)

Scientific Theories and Falsifiability

1. Scientific definition of a theory + a fact, theory of evolution + empirical evidence
2. Theory: a coherent set of testable hypotheses that attempt to explain facts about the natural world (i.e. not just an assumption based on limited knowledge)
3. Fact: an assertion for which there is so much evidence that it would be perverse to deny it (-Gould)
4. Test a theory by attempting to falsify it; theories graduate to “fact-hood” after repeated testing fails to falsify it
5. Unfalsifiable assertions are not scientific

Development of the Theory of Evolution

1. Bacterial antibiotic resistance is one of Canada’s top health issues
2. Penicillin (discovered by Fleming, 1928) used to be able to kill most infections by inhibiting the function of an enzyme required for cell wall biosynthesis and was used widely in the 1950s+ but now is basically resistant 
3. Resistance increased because of overuse/misuse of antibiotics, and their inclusion in animal feed
4. Rate of developing new antibiotics doesn’t keep up with the rate that bacteria are becoming resistant
5. Evolution: species change over time
6. Plays a central role in our understanding of life (common features, diversity, changes, etc)
7. Evolution is variational and not transformational
8. Early view: life is unchanging
9. Aristotle: Scala Naturae (non-living, cells, fungi, algae, plants, invertebrates, vertebrates, humans, God)
10. Organisms specially created by God, species don’t change or go extinct, new species can’t arise
11. 14th century: Biological research was dominated by natural theology 
12. Linnaeus (18th century): tried to classify all organisms, binomial species classification system (similar-looking organisms groups together and then sorted)
13. Didn’t credit the similarities between organisms to anything other than God
14. Lamarck: challenged idea that organisms can never change
15. Inheritance of acquired characteristics (is false)
16. Proposed “perfecting principle”: simple organisms evolved into more complex ones (up Scala Naturae) and simple life came from non-living organisms
17. Darwin: on HMS Beagle around the world, was well educated but not v experienced (probably a good thing: had no pressure to conform to popular ideas), was v observant, took objective notes and took lots of specimens to ship back to England
18. Wasn’t the first to propose that organisms changed, but he arrived at how evolution might occur
19. His major insights came from geology and fossil record, geographic distribution of species, comparative morphology of species  
20. Geology + fossil record
21. Read Lyell’s “Principles of Geology,” who supported Hutton’s ideas that Earth’s surface was constantly changing due to natural events (e.g. earthquakes, volcanoes, etc) vs ancient/supernatural events (e.g. Noah’s flood)
22. Witnessed a powerful earthquake in 1835 Chile (Concepcion) and the changes that followed
23. Found marine fossils in Andes Mountains at h = 4000 m → confirmed this
24. Set Darwin to think that life may also change slowly over time 
25. Was aware that fossils of things that didn’t look like living species have been discovered
26. Living armadillos and fossilized glyptodonts had similar armour but why weren’t there any glyptodonts living? → Armadillos are descendants of them
27. Geographic distribution of species: 
28. Biogeography: why are some species spread out and some not, why some species far away from each other are so different and why some are similar 
29. Observed that none of the oceanic islands he visited had land mammals (only flying mammals), and species in islands were similar to species on nearby continents
30. Galapagos islands: many animals, looked slightly diff on diff islands, resembled animals in South America → they’re related but changed over time
31. Comparative morphology: 
32. Example: human arm, flippers of seals, foreleg of pigs, bat wings look very different but share an underlying structure 
33. Natural theologians can’t explain body parts w no apparent function
34. Buffon said that some animals changed since creation; they had a purpose in ancestral organisms and now don’t (but didn’t know how it happened)
35. Darwin explained vestigial structures using the idea of common ancestors
36. Homology: similarity due to a shared ancestor between organisms in different taxa
37. Wallace was also doing careful research and came to similar ideas about natural selection → sent his findings to Darwin → Darwin didn’t want Wallace to publish before him → published On the Origin of Species by Means of Natural Selection 
38. Malthus: influenced both Darwin and Wallace
39. Wrote An Essay on the Principle of Population: humanity is destined for disaster (population>>>food)
40. Clarified to Darwin how population and food are related (not all offspring grow up: “struggle for existence”)
41. Selective breeding/artificial selection 
42. Darwin realized that individual organisms don’t change over lifetime, but populations change
43. Natural selection
44. Organisms have a large capacity to reproduce but limiting resources constrain size of population → individuals within population compete for resources
45. Individuals differ in certain traits (e.g. size, colour, behaviour) that are inherited → organisms with traits that help them get the resources can reproduce more
46. Darwin’s mockingbirds: descent with modification
47. One species of mockingbird came from South America and colonized the islands, and specific traits became more common in diff islands as they adapted to the diff food sources, microclimates, etc
48. Study of this was complemented by his finch studies
49. Impact of Darwin’s study: generalized evolution to everything, underlying homology indicated that there’s a common ancestor
50. Fitness: describes an individual’s reproductive success
51. A relative concept (you only have to be better than other ppl to be fit)
52. A trait is only valuable if it increases fitness
53. The traits that increase fitness might change over time
54.  Gregor Mendel published his pea plant research around the same time as Darwin’s paper
55. 50 years later, Morgan discerned that genes are carried on chromosomes
56. Helped scientists form the modern synthesis of evolution (genetics + natural selection)
57. Random mutations causes variation in a population (i.e. natural selection directs which mutations survive)
58. Natural selection is a theory of evolution: heritable variation leads to differential survival and reproduction; supported by experimental and observational science
59. Note: natural selection acts on the phenotype, not the genotype
60. Examples
61. Peppered moth (Biston betularia) during industrial revolution: carbonaria (black) and typica (light) 
62. Stickleback (Gasterosteus aculeatus): freshwater ones have no spines and bony plates (less predators, prevents dragonflies to attack young sticklebacks, don’t need to bear the metabolic costs of having them)
63. Expression of Pitx1 gene is absent in the embryonic buds where fins develop (mutation to a regulatory gene)
64. Occurs very slowly in bigger animals due to generation time (average difference in age between parent and offspring)
65. Short generation time organisms (e.g. bacteria) can be used to study evolution
66. E. coli adapting to temperatures
67. Darwin said that we should look exclusively at an animal’s direct (lineal) ancestors, but it’s hardly ever acc possible
68. Natural selection is not the same as evolution: natural selection is a major mechanism (not the only one) that causes evolution
69. Homologous structures: similarity suggests common ancestor
70. Analogous structures: similar structures in unrelated organisms

Why Evolution is True

1. Humans are still evolving: increasing protection against malaria, lactose intolerance, etc 
2. Do ppl think evolution is true?
3. Difficult for some ppl to reconcile this theory with their beliefs on the origins on humans
4. Over time, more ppl are thinking that evolution occurred without God
5. Theory of evolution (populations of organisms change over time, and all organisms are related)
6. Evolution considered as a scientific theory but not creationism/intelligent design 
7. Theory of evolution is testable, falsifiable (can be contradicted by evidence)
8. Historical and continued evidence supports the validity of the theory of evolution
9. Falsifiable theory/conjecture:
10. Is able to be measured
11. Open to the possibility that it is wrong (e.g. there is no tiny teapot in outer space)
12. Points to hypotheses that need testing and evidence
13. Falsification starts a critical discussion (leads to more ideas abt how things work, forming a revised theory)
14. Not falsifiable if it needs an exhaustive search of all possibilities to disprove it (e.g. a tiny teapot is in outer space)
15. A falsifiable statement needs just one observation to disprove it
16. Evidence for evolution
17. Biogeography: similar species are found in distant places
18. 3 different types of flightless birds only live in South America, Africa, and Australia. Supports evolution bc if there was going to be a form of flightless bird, there’d only be one form, but there are 3+ species
19. Comparative morphology: 
20. Pig leg, dolphin flipper, bat wing: have different functions, but similar bone structures. Supports evolution bc it indicates a common ancestor 
21. Addresses vestigial structures (e.g. pigs have toes that don’t touch the ground): organisms are not perfect, structure must have had a function in an ancestral organism
22. Geology: changes in geology are slow and gradual (over billions of years)
23. If we acknowledge that the changes on the Earth have been going on for billions of years, there’s lots of time for evolution to have happened
24. Fossils: evidence that life on Earth today is different from the past
25. Lamarck proposed an idea for how evolution happens: inheritance of acquired characteristics (individuals change through lifetime and pass these changes on to offspring)
26. Charles Darwin (published “On The Origin of Species” in 1859):Natural selection (“descent with modification” from a common ancestor) is a mechanism to explain evolution
27. There is variation for traits in a population
28. Individuals whose traits allow them to survive better (higher fitness) leave more offspring who inherit these traits
29. Over time, individuals with these favourable traits become more common in the population (adaptation)
30. Evolution is variational, not transformational: individuals differ in phenotype, and success so populations change (instead of individuals changing and passing on these changes to offspring)
31. Gradualism: takes many generations to produce large evolutionary changes (i.e. many transitional forms)
32. Selection is not directed towards any specific goal; a population cannot “want” to evolve
33. Adaptations didn’t evolve on purpose even though they can be well suited to an environment
34. Living things aren’t always perfectly suited to the environment (environment can change, limited genetic variation in population, compromise between competing demands)
35. Example (environment): snowshoe hare in a non-snowy landscape isn’t camouflaged
36. Example (competing demands): some male birds are bright and showy are good to attract a mate and reproduce, but also call attention to themselves from predators
37. All life is related through common ancestry: LUCA (Last Universal Common Ancestor), a primitive entity who lived more than 3.5 billion years ago

New species form when an ancestral lineage divides into daughter lineages