2400 final

fever

evolved as a defense mechanism to fight infection by pathogens

endotherm

maintain a stable internal body temp by generating heat through metabolism

ectotherm

animals that rely on external sources like the sun to regulate body temps

inducing fever

the desert iguanas induces fever behaviorally in response to bacterial infection

endothermic and ectothermic vertebrates induce fevers to respond to infections

fever in humans

costs of running a fever

• increased metabolic rate

  • 2-3 degree C rise = 20% increase

  • shivering = up to 6x metabolic rate

patients who receive fever reducing drugs recover less quickly

why is fever beneficial?

H1: higher temps may harm the pathogen more than the host

H2: higher temps reduce growth rates of microorganism- doesn’t apply to all bacteria

H3: fever triggers the expression of heat shock proteins, which stimulates immune cell activity and helps cells deal with intracellular damage

why are fevers so common?

smoke detector principle

• must be very sensitive to keep body safe

why are we vulnerable to disease?

1. we’re locked in a coevolutionary arms race with pathogens, and they evolve more rapidly

2. nat selection has not had enough time to catch up with environmental change

3. the laws of physics and biology impose trade-offs on what an organism can do

4. nat selection lacks foresight, we are stuck with relics of our past

5. nat selection favors reproductive success, even at the expense of vulnerability to disease

6. some defenses (fever, nausea, anxiety) are unpleasant but they’re beneficial adaptations rather than maladies

thicker bone structure would result in less breaks, but at cost of speed and nimbleness

evolutionary body plans not well suited to bipedal locomotion- eg spinal column holds weight

coevolutionary arms race: pathogens-host

pathogens typically have large pop sizes with shorter generation times

leading to more genetic variation via mutation for natural selection to act on

immune strategies

host pops could never keep up via adaptive substitution rates so it has relied on diff strategies:

1. detecting characteristic components of pathogens

2. finding infected cells

3. creating variation through sexual reproduction

detecting characteristic components of pathogens

pathogens have essential highly conserved components known as pathogen-associated molecular patterns (PAMPs)

our immune system uses pattern recognition receptor molecules to detect these PAMP’s

finding infected cells

what makes viruses difficult to find?

1. have few conserved external structures

2. many were produced by budding from host cell- wrapped in a membrane layer structurally the same as the host cell

3. replicate within a host cell- need to find infected host cells in addition to the free virus

distinctive characteristics the immune system can target:

• form double stranded RNA during replication

• viral nucleic acids

• viral coat proteins

• etc

hosts learn to detect pathogen cues throughout their lifetime

the immune system produces an enormous, highly diverse repertoire of T cells that recognize infected cells and B cells

V(D)J recomb

clonal selection

clonal expansion

V(D)J recombination

variable-diversity-joining rearrangement

mechanism of somatic recomb that occurs only in developing immune cells

• creates millions of diff receptors by combining a small number of subunits in diff ways

clonal selection

a process to produce a large repertoire of immune receptors via somatic recomb

clonal expansion

an antibody binds to an antigen and it begins to proliferate rapidly

creating variation through sexual reproduction

sexual reproduction generates large amounts of variation

if pathogens are transmitted vertically:

• asexual reproduction- identical genotypes- more susceptible to pathogens

• sexual reproduction - diff genotypes- less susceptible to pathogens

pathogens have evolved counter measures

1. avoid detection

2. sabotage or deceive the immune system

human immunodeficiency virus

poxviruses

some bacteria

human immunodeficiency virus

downregulates the major histocompatibility complex (MHC) that helps recognize t=infected cells

induces programmed death in uninfected cells

poxviruses

produce enzymes that degrade the immune systems chemical signals that control replication and migration of cells to fight infection

produce decoy receptors to divert signals from true agents

some bacteria

tap into inhibitory pathways to control the hosts inflammatory response

secrete enzymes that degrade immune signaling molecules

normal looking pathogen phylogeny

immune response generates lifelong immunity

pathogens cannot evolve escape variants that can dodge immune memory

chronogram shows longer branch lengths, with older nodes

cactus shaped pathogen phylogeny

immune response does not generate lifelong immunity

pathogen generates escape variants capable of reinfecting an ind

short branches with recent nodes

single trunk with twiggy spines branching off

evolution of virulence

early theories:

• pathogens should evolve to reduce virulence and minimize the cost imposed on their host

• killing their host is not in their “evolutionary interest” as it need the host to reproduce and spread

virulence

the degree of harm a pathogen causes its host

can be measured as the fraction of infected inds that die- infection mortality rate

case study: myxoma virus in australian wild rabbits

19th century- wild rabbits were introduced to australia but they had devastating effects on the ecosystem

1950’s- introduced the myxoma virus to control rabbit pop

myxoma dropped from 99% to 60% in the wild, still extremely virulent

in the lab, mortality rate slightly decreased with time (90%-60%), but was still high

epizootic

a disease outbreak

trade-off theory of virulence

rapid exploitation kills the host decreasing transmission

grow too slowly and immune system will clear you quicker

best applied on a case-to-case basis

consider:

1. vertical vs horizontal transmission

   1. some empirical support

2. multiplicity of infection (multiple strains = variation in virulence)

   1. some empirical support

3. mode of transmission: direct vs vector

   1. lacks support

covid-19 pandemic

what should we have anticipated for the virulence of this pathogen?

• transmission occurs within the first 1-2 weeks of infection

• symptoms occur after ~2 weeks

• death typically occurs several weeks later

selection for increased virulence more likely

2020-2022 virulence stable

omicron and delta variants had increased virulence

caveat- difficult to measure virulence- treatment got better with time

biggest drive of reduced fatality rates in humans associated with immune system learning rather than nat selection on either the virus or the host

top causes of mortality in humans

1. automobile accidents

2. poisoning

3. falls

4. choking

phylogenetic constraint and choking vulnerability

why did we evolve to have such an unfortunate intersection between the trachea and esophagus?

epiglottis as a safety mechanism but still not ideal

benefits of current structure:

• mouth provides a backup airway if nose is clogged

• facilitates complex vocalizations (human speech)

consequences of phylogenetic constraint

lungs arose early in primitive fish to trap gas bubbles by gulping via mouth

tetrapods- gills were lost die to the evolution of lungs

lungs developed from the esophageal tissue and could not be decoupled

phylogenetic constraint in dogs vs humans

dogs can eat and breathe at the same time bc their soft palate and epiglottis meet

human trade off

• a descended larynx in humans enables human speech (needs air to create sound)

• a descended larynx in humans exacerbates choking hazard

humans are vulnerable to choking, could be worse

octopus brain wraps around esophagus

each bit of food must pass through the middle of the brain

each bite can have disastrous consequences if too big

senescence

the decline in the physical functioning or performance of living organisms with age

similar structures are seen as fertility declines with age

it is a general phenomenon among multicellular organisms

rate-of-living hypothesis

senescence is an unavoidable consequence of accumulated physical wear and tear

two predictions:

1. if selection has done everything possible to slow senescence, there is little to no genetic variability in the senescence rate

2. strong inverse correlation between metabolic rate and life span across species

if selection has done everything possible to slow senescence, there is little to no genetic variability in the senescence rate

evidence contradicts this!

identified longevity mutations that slow senescence in various model organisms (APOE2 allele in humans)

life span is a heritable trait

there is considerable genetic variations

strong inverse correlation between metabolic rate and life span across species

high metabolic rates → increase in oxidative stress → intracellular damage

skepticism:

1. longevity mutants

2. within a species longevity and metabolic rate are not associated

3. exercise increases metabolic rate but doesn’t decrease longevity

4. ex. birds typically have longer life spans than mammals of comparable metabolic rate

early vs late mutations

average reproductive success is proportional to the average reproductive life span

inds with late-acting mutations have higher reproductive success than inds with early-acting mutations

deleterious mutations acting early in life will be under stronger selection

deleterious mutations acting late in life will be under weaker selection

mutation accumulating hypothesis

for late-life traits, selection is not strong enough to purge deleterious traits

deleterious mutations build up in genomes

predicts genes expressed early in life are under stronger selection than those expressed later in life

antagonistic pleiotropy hypothesis

a gene that provides an advantage early in life has deleterious effects later in life (or vice versa)

antagonistic pleiotropy

testosterone:

• early/mid life: boosts muscle mass, immune function, competitive ability, and reproductive success- all things selection loves

• late life: associated with increased risk of prostate cancer and cardiovascular disease

p53:

• early life: aggressively suppresses cancer by triggering cell death in damaged cells- clearly beneficial

• late life: same aggressiveness may contribute to tissue aging by eliminating too many stem cells over time, reducing the body’s ability to repair itself

1925: The state of Tennessee v. John Thomas Scopes

1925- a high school teacher was accused of violating the Butler Act, a law which outlawed the teaching of human evolution in public schools

scopes was a teacher represented by the american civil liberties union and defended by Clarence Darrow

william jennings bryan, a 3-time presidential candidate and former secretary of state, argued for the prosecution

scopes lost and was fined $100

became famous bc:

• staged acts to bring attention to the town (monkeys)

• Darrow took unorthadox step of calling Bryan, counsel for the prosecution, as a witness to question him on the Bible as an expert

• darrow embarrassed bryan and got him to contradict himself

• teaching of evolution continued to be prohibited in some states for many years

1968: Epperson v Arkansas

1927: “unlawful” for any teacher to say that evolution from animals was real in public school

1958: soviets launch sputnik and congress passes the national defense education act, promoted a textbook teaching evolution

1968: teacher Susan epperosn from little rock wanted to use new textbook

in 1968, US Supreme court unanimously ruled in this case that laws prohibiting teaching evolution violated the establishment clause of the 1st amendment

how long ago did the first hominins arise?

> 2 million yrs ago

hominin

an member of the human lineage after its split from the chimpanzee lineage

how many hominin species have been discovered?

> 15

high altitude adaptation in humans

half of Tibetan ppl live above 3,500 m while 600,000 ppl live above 4,500 m

above 4,500 m there’s < 2/3 pO2 (crops don’t grow and hard to breathe)

Tibetans have been living, working, and raising their families here for thousands of years

EPAS1 locus

contributes to high altitude tolerance by increasing blood flow and through other mechanisms

genetics and simulation studies suggest the EPAS1 locus was introduced via interbreeding

genome sequences at EPAS1 came from extinct group of Denisovan hominins

Tibetan closer related to Neanderthals than to modern humans

evolutionary relationships among great apes

humans are more closely related to the chimpanzee and bonobo

highly supported by genetic analysis

but in 20% of loci, humans are more closely related to gorillas than chimpanzees

reason two distinct branches may share common characters

1. homoplasies

2. symplesiomorphies

3. deep coalescence

deep coalescence

incomplete lineage sorting or retention of ancestral variation

more likely in branches with few numbers of generations (short branch) and large pop size (wide branch)

hominin clade

not well received since all other species are extinct

has relied exclusively on fossil evidence until advances in sequencing ancient DNA have now made it possible to better understand their complex evolutionary history

hominin

an member of the human lineage after its split from the chimpanzee lineage

hominin evolution is not linear

multiple branching events lead to multiple species that are now extinct

~20 distinct species

humans have been the only hominin representative in only the last 30,000 yrs

bipedal locomotion

the most important change in early hominins

ability to walk upright

main differences between hominins and chimpanzees

1. loss of canines

2. skeletal structure for bipedal locomotion

first hominins are challenging to place due to:

1. poor fossil quality

2. difficult to tell whether a fossil belongs to a hominin or panin (chimpanzee) lineage

archaic hominins

fully capable of bipedal locomotion and share numerous traits w homo sp.

smaller brains compared to humans

walked upright (at least part time)

used tools

evidence suggests one or more species used stone tools to scavenge for meat

megadont archaic hominins

megadont = big teeth

protruding cheek bones anchored massive chewing muscles and big teeth well suited for grinding low-quality food sources

traditional hominis

~2.3 mya the first members appeared

smaller brain than modern humans but shared other similar morphological characters

greater cranial capacity than archaic hominins

abundant use of tools

premodern hominis

homo erectus appeared in africa, europe, and asia 1.9 mya

taller, longer legs

larger brain

more elaborate tools

began using fire to cook and provide heat ~400,000 years ago

neanderthals used fire to create pitch (tar) from birch snap to attach stone tools to handles

wrengham’s cooking hypothesis

morphological changes, shifts in life history strategies and behavior were all driven by fire technology

cooked food is easier to digest

offers larger energetic stores

supporting evidence:

• smaller jaw and molars

• decreased size of digestive tract

• increases in female body mass

believed hominins controlled fire prior to 4000,000 years ago, little evidence

homo heidelbergenesis

appeared ~800,000 - 500,000 years ago

hunted bigger game than predecessors

levallois technique (mode 3)- more elaborate tools

homo sapiens evolved from them ~200,000 - 300,000 years ago

homo florensiensis

discovered in 2004 in the Liang Bua cave in the Indonesian island of Flores

initially thought to be a deformed H. sapiens

their location on the phylogeny is still highly debated

characteristics:

• small stature

• similar face geometry to H. sapiens

• used tools, fire, hunted prey

h. naledi

fossil discovered in 2015 in South Africa’s Rising Star cave system - ongoing research

limb morphology resembles archaic hominis

1.5 meters tall and weighed ~45 kg

bodies appear to have been placed in the shaft to fall to the chamber in a form of burial

H. erectus and H. heidelbergensis underwent a remarkable expansion

what allowed them to migrate?

• evolved physiology

mode 1

rudimentary tools

mode 2

slightly advanced tools

mode 3

advanced tool use

evidence for out of africa migration model

1. archeological evidence of toolmaking technologies reveals consecutive waves from africa

2. fossil evidence=

   1. gradual divergence of premodern humans

   2. modern humans arise first in Africa (~200,000 - 130,000 years ago)

   3. expansion of H. sapiens beyond africa ~60,000 years ago replacing other homo forms

3. genetic data (mtDNA) supports this model the best

   1. mtDNA diversity highest in africa

   2. MCRA of mtDNA of humans dates to emergence of homo sapiens in fossil record in africa

declining diversity with distance from africa

neanderthals

heavier, stronger, and stockier

mode 3 tools and hunted large game

cooked w fire

cared for their sick, wounded, and elderly (fossil evidence)

buried their dead

denisovans

known from a single bone and a couple teeth found in the altai mounatins

genome sequencing has allowed is to understand a great deal

homo sapiens

appeared in africa (200,000 - 130,000 years ago)

larger brain

slender body with longer limbs

upper paleolithic revolution:

• used bone and ivory for tools (mode 4)

• created elaborate shelters

• produced art and musical instruments

• hunted larger game

• ceremonial burials

evidence suggests interbreeding between H. sapiens and neanderthals

fossil record suggests interbreeding

mtDNA suggest limited to no interbreeding

nuclear DNA shows interbreeding

due to interbreeding or deep coalescence?

we share 1-4% of of their genome

pops found geographically closer share more of their genome

INTERBREEDING!

denisovans and homo sapiens also interbred in eurasia

structural analysis of modern humans

based on ancestral groups in HW Equilibrium

structure can identify regional differences at finer scales

host-pathogen coevolution reflects human migration history

h. pylori gut bacteria

found in half of the human pop worldwide

transmitted vertically from parents to offspring

structure reflects continental groupings

personal genomics

prior to ~2015 you could obtain a full health report with risk factors for dozens of diseases on 23andMe

in 2015 FDA rules that 23andMe’s health component required their approval → 23andMe then provided ancestry and then extremely limited health info

2021 - value $6 billion

2024- a massive data breach exposed the DNA and personal data of 6.9 million users. hackers specifically targeted customers of Ashkenazi Jewish and Chinese ancestry leading to a class-action lawsuit and $30 million settlement

2025- bankrupt, CEO resigned. TTAM research institute, founded by old CEO outbid new buyer for $305 million

coevolution

reciprocal evolution of two or more species that interact

changes in one species drive evolutionary changes in the other and vice versa

likely to occur under:

• predator/prey, parasite/host

• competitive species

• mutualistic species

obligate mutualism

need each other to survive and both benefit

lichens

made up of two different species

1. fungal

2. photosynthetic algae or bacteria

do mutualistic relationships require rapid evolutionary changes?

yes

fast evolutionary change seems to be associated with a mutualistic lifestyle

requirements of coevolution

two or more entities

reciprocal evolutionary change (both entities A and B evolve in response to each other)

reciprocal impacts on fitness

specific adaptation to the partner (not general traits)

evolutionary feedback (change in A causes change in B causes change in A…)

coevolution pays out in 2 ways

1. mutualism- evolutionary changes in each species benefit each other

2. antagonistic coevolution- each species decreases the fitness of the other: “Evolutionary Arms Race”

diffuse coevolution

coevolutionary relationships that involves 3+ species

panic grass lives in hot soil and Yellowstone National Park

survival depends on the fungus C. protuberata

which in turn requires the thermal tolerance virus

coevolution and mutualism

how did mutualism evolve?

1. neutral interaction

2. commensalisms- one partner benefits and the other is neutral

3. antagonistic relationships

4. mutualistic relationships

ant-fungus mutualisms

ant-fungal mutualisms began ~50 mya when ants began cultivating their own food

ants promote fungi growth and eat mycelium from other fungal partners

leaf-cutter ants host bacteria that produce antibiotics to protect their fungal food supply

ant-butterfly mutualism and the role of communication

butterfly larvae and pupae secrete a sugary nectar that nourishes the ants

ants protect the larvae from predators such as wasps

butterfly pupae produce vibrational signals to communicate with ants whom are nearly deaf

communication in a bat-pitcher plant mutualism

pitchers provide the bats with a parasite-free environment and microclimate

wooly bat guano increases nitrogen intake in plants by 34%

problem: pitchers are rare, borneo has thick vegetation with closely related plants

pitchers are good reflectors of ultrasonic sound

mutualism and the response to cheaters

soybean legume provides energetic resources (carbs) for bacteria growth and maintenance

rhizobial bacteria converts inorganic N2 to organic N2 (plant growth and synthesis)

G. max punished the bacteria by changing the permeability in their membrane, reducing available energy resources to B. japonicum → decreased size

can lead to co-speciation

antagonistic coevolution

when two species have a negative effect on each other’s fitness

two main forms

1. predator-prey

2. parasite-hots

predator-prey coevolution

predator whelk (sinistrogulgur) vs bivalve prey (mercenaria)

fossil record evidence

• mercenaria evolved thicker shells

• sinistrofulgur evolved larger sizes

host-parasite coevolution and speciation

lice have cospeciated with humans, chimps, and gorillas

head and clothing lice were hypothesized to have diverged 83,000-170,000 when humans began wearing clothes

• but in reality a gorilla lice jumped to humans 3.3 mya and subsequently speciated

as host pops diverge (to speciation), their parasite is exposed to new selective pressures, likely resulting in cospeciation

mimicry and coevolution

bayesian mimicry: palatable species resembles an unpalatable one

aposematic coloration: warning coloration for venomous/unpalatable species

mullerian mimicry: mimicry between two unpalatable species reinforce their toxic signals

testing bayesian mimicry theory

western scrub jay overlaps with the toxic CA newt, but not the mimic

scrub jays took longer to first contact the toxic and non-toxic mimic vs the nontoxic control

nontoxic mimic has higher survival

mosaic coevolution

when two species interact mutualistically in some communities and antagonistically in others

woodland star attracts moths to pollinate

moth lays its eggs in the flower

the more reliant the plant is on the moth the more mutualistic their dynamics are

gene-culture coevolution

culture transmission: transfer of info from ind to ind through social learning or touching

when cultural transmission leads to changes in the frequency of traits within or between generations = cultural evolution

cultural evolution in birdsongs of Darwin’s finches

medium and cactus groundfinches produce viable hybrid offspring

observation: father and son finches have similar songs (but are significantly diff between species)

H1: birdsong is a genetic trait

H2: birdsong is culturally inherited

95% of females only mated with males who sang their song sang by most of the males of their species

cultural transmission is a barrier for cross-species breeding

gene-culture coevolution and lactose intolerance in humans

adults were lactose intolerant when cattle domestication began

people learned to ferment milk, reducing the amt of lactose

a point mutation in the LCT gene allowed lactose digestion

LCT gene spread quickly to reach a frequency of ~80% td

cooperation

the process of working tg to the same end

problems:

1. altruism- favoring another’s fitness at the cost of your own

2. free-riders- receiving the benefits from others without cooperate or show altruistic behaviors when they could free-ride instead

3 evolutionary paths to cooperation

1. kinship

2. reciprocity

3. group selection

sociality

the tendency of individuals to live and interact in groups, forming communities with links