Lecture 3
The central role of parasites in
evolution
The central role of parasites in evolution
J.B.S. Haldane (1892-1964)
J.B.S. Haldane
•
The son of a famous physiologist, he had a long history of
using himself as a guinea pig in experiments with
poisonous gases (along with his dad)
•
Once lost two teeth, which exploded due to the rapid
decompression in his sinuses, during one experiment
“Four stages of acceptance: i) this is
worthless nonsense; ii) this is an interesting,
but perverse, point of view; iii) this is true, but
quite unimportant; iv) I always said so.”
J.B.S. Haldane (1892-1964)
•
Though never awarded a doctoral degree, he made
seminal contributions in several fields including
biochemistry, enzymology, physiology
•
In 1932 published The Causes of Evolution, a landmark
in reconciling the theories of natural selection and
Mendelian genetics
•
Held the Galton Chair in Biometry, University College
London, 1937-57
•
A visionary, who, earlier than perhaps anyone else, saw
the importance of infectious disease in evolution
Disease and Evolution, 1949
•Obtaining food and mates and protection against
“natural” forces such as cold, or predators, is only
part of the story
•Useful to distinguish at this point between an
organism’s abiotic and biotic environment
-abiotic?
-biotic?
Disease and Evolution, 1949
•Of these, the biotic environment is probably
much more important evolutionarily
•“I want to suggest that the struggle against
disease, and particularly infectious disease,
has been a very important evolutionary
agent…”
Disease and Evolution, 1949
•How important is disease as a killing agent
in nature?
•One general trend may be disease as a
density-dependent check on population
growth (along with lack of resources, space)
•Why density dependent?
•The impacts of disease will of course differ
for different species…How about for
humans?
Disease and Evolution, 1949
Disease and Evolution, 1949
Disease and Evolution, 1949
•Huge difference
between developed
and developing world
•Infectious disease still
kills > 1/3 of people
worldwide
•Mostly in developing
countries (big
populations) and
mostly kids
Disease and Evolution, 1949
•How do you think infectious disease has impacted the
human population through history (and pre-history)?
Disease and Evolution, 1949
•“A disease may be an advantage or a disadvantage to a
species in competition with others”
•Example of different cultures of Drosophila immune, or
not, to a bacterial pathogen
•Example of wild southern African ungulates infected with
trypanosomes
•Impossible to introduce cattle in such areas, and even
African breeds have not had time to evolve immunity
•Native species (more to the point, individuals) are at an
advantage because of the parasite, an important part of
the biotic environment
Disease and Evolution, 1949
•“Europeans have used their
genetic resistance to such
viruses as that of measles as a
weapon against primitive as
effective as fire-arms”
•What other episodes in
evolutionary history have been
due to infectious disease
rather than the sorts of
adaptations we tend to focus
on?
•http://viscog.beckman.uiuc.edu/g
rafs/demos/15.html
Disease and Evolution, 1949
•“In all species investigated the genetical diversity as
regards resistance to disease is vastly greater than that as
regards resistance to predators.”
•“It is much easier for a mouse to get a set of genes which
enable it to resist [bacteria] than a set which enables it to
resist cats.”
•These remarks have been borne out by decades of study
Disease and Evolution, 1949
Other ideas/speculations in his paper:
•
Large amount of unexplained biochemical diversity in
serological tests may play a part in disease resistance
(outlines tests for associations between, say, diptheria
susceptibility and various blood groups)
•
Genes for generating resistance variation should be
particularly mutable, as long as other genes not
affected
• Negative and positive frequency-dependent selection:
(when be rare or common is selectively advantageous)
Disease and Evolution, 1949
•
Pathogen-driven speciation
•
“Once a pair of races is geographically separated, they
will be exposed to different pathogens. Such races will
tend to diverge antigenically, and some of that
divergence may lower the fertility of crosses.”
Disease and Evolution, 1949
• Social aspects of disease
“It will be on the whole an antisocial agency…it is doubtful
that many birds could survive the faecal contamination
which characterizes the colonies of many sea birds.”
•
Evolutionary psychology and Darwinian medicine:
“A vast variety of apparently irrelevant habits and instincts
may prove to have selective value as a means of
avoiding disease.”
Examples?
Disease and Evolution, 1949
•
evolution of virulence:
“Perhaps the theory that most diseases evolve into
symbioses is somewhat Panglossist. I doubt if it
occurs as a general rule, though it may do so.”
Panglossist?
Do most diseases evolve into symbioses?
Disease and Evolution, 1949
Given enough time a state of peaceful coexistence
eventually becomes established between any host and
parasite.
-Rene Dubos
Disease and Evolution, 1949
•He also notes that resistance to disease is rarely
absolute, in part because viruses and bacteria evolve so
quickly
•“The most that the average species can achieve is to
dodge its minute enemies by constantly producing new
genotypes, as the agronomists are constantly producing
new rust-resistant wheat varieties.”
•The banana clone (a word that Haldane coined) ‘Gros
Michel’ was widely exported, but has been all but wiped
out by a fungal root pathogen
Disease and Evolution, 1949
http://www.gi.alaska.edu/ScienceForum/ASF9/977.html
•Although commonplace today, bananas only became a
staple in North America's diet late in the 19th century.
•They could do so because of a genetic freak--a
spontaneous mutation in a kind of banana native to
Southeast Asia.
•The new banana was triploid, big, sweet, and seedless
•The new mutation also had a characteristic that made
long-distance transport possible: all the bananas on a
stalk ripen at once, about three weeks after they've grown
to harvestable size.
Disease and Evolution, 1949
•The French transported cuttings of the new plant to the
Caribbean, where it thrived. They named it Gros Michel.
•The Gros Michel was a true commercial banana, and the
variety that won the hearts of people living outside the
tropics.
•Gros Michel had a serious weakness: it was susceptible
to two kinds of fungus diseases.
•One, called yellow sigatoka, could be controlled by
spraying. The other was soil-borne Panama disease, a
kind of fusarium wilt, and could not be cured or prevented.
Disease and Evolution, 1949
•The growers' only option was to keep moving banana
plantations to fresh land. By the 1960s, new land ran out
•Instead, they found a new banana. This one, christened
Cavendish, was discovered in a Saigon botanical garden.
It too was a big, sweet, seedless triploid that ripened
weeks after harvest, but it resisted Panama disease.
Swiftly and with no fanfare, Cavendish bananas replaced
Gros Michel.
•The Cavendish is now the banana of commerce.
Case study I: Parasites and the advantage of sex
Which reproductive mode is better: sexual or asexual?
QuickTime™ and a
TIF F (Uncompressed) decompressor
are needed to see this picture.
John Maynard Smith
•
JMS died recently
•
Student of Haldane
•
Aircraft engineer in WWII,
came to biology later in
life
•
Leading thinker on the
“evolutionary scandal” of
sex
•Sex is costly, not to mention complicated and
dangerous
•Searching for mates takes time and energy, and has
risks (?)
•Potential mates may demand additional exertion or
investment before mating
•After all that, mating might prove to be infertile
•Why go to all the trouble?
Case study I: Parasites and the advantage of sex
Which reproductive mode is better: sexual or asexual?
Null model: (what a null model?)
1. A female’s reproductive mode does not affect the
number of offspring she can make
2. A female’s reproductive mode does not affect the
probability that her offspring will survive
(John Maynard Smith, 1978)
QuickTime™ and a
TIF F (Uncompressed) decompressor
are needed to see this picture.
Case study I: Parasites and the advantage of sex
Which reproductive mode is better: sexual or asexual?
•
Imagine a population founded by three individuals: a
sexual female, a sexual male, and an asexual female
•
Every generation each female produces four offspring,
after which the parents die
•
All offspring survive to reproduce
•
Half the offspring of sexual females are female (the
other half are male) but all the asexuals’ offspring are of
course female
•
What happens?
In a population conforming to JMS’s assumptions,
asexual females produce twice as many grandchildren
as sexuals, and fraction of asexuals climbs
•Asexuals should take over. And yet the vast
majority of multicellular species are sexual.
•What’s going on?
•JMS’s model illustrates, as he intended it to,
that these facts represent a paradox for
evolutionary theory
•It’s an evolutionary scandal!
•Sex must confer benefits that allow it to persist
in spite of the strong reproductive advantage of
parthenogenesis.
•The benefits must lie in the violation of one or
both of those assumptions….
1. A female’s reproductive mode does not affect the number of
offspring she can make
2. A female’s reproductive mode does not affect the probability
that her offspring will survive
•The first assumption is actually violated in species in
which fathers provide resources or parental care
essential for producing young.
•This includes humans.
•But such species are in the minority. In most species,
males contribute only genes.
A general advantage to sex is thus likely to be
found in violation of the second assumption…
•What might account for a difference in the probability of
survival between sexual and asexual offspring?
•Asexual reproduction (clonal) mode means offspring
are identical to parent (mother)
•Sexual mode leads to diversity.
Mutant forms of genes can spread easily through a
population
Recombination: the formation of hybrid DNA molecules
combining genetic information from two sources into a
new mosaic
(it’s a double-edged sword….Why?
•By the late 1980s, in the contest to explain sex, only
two hypotheses remained in contention.
•One, the deleterious mutation hypothesis, was the idea
that sex exists to purge a species of damaging genetic
mutations
•Alexey Kondrashov has been its principal champion
•He argues that in an asexual population, every time a
creature dies because of a mutation, that mutation dies
with it. In a sexual population, some of the creatures
born have lots of mutations and some have few. If the
ones with lots of mutations die, then sex purges the
species of mutations. Since most mutations are harmful,
this gives sex a great advantage. (imagine cars in a
junkyard…)
•The main defect in Kondrashov's hypothesis is that it
works too slowly.
•Pitted against a clone of asexual individuals, a sexual
population must inevitably be driven extinct by the
clone's greater productivity, unless the clone's genetic
drawbacks can appear in time.
•Currently, a great deal of effort is going into the testing
of this model by measuring the deleterious mutation
rate, in a range of organisms from yeast to mouse. But
the answer is still not entirely clear.
•In the late 1980s the Red Queen hypothesis emerged,
and it has been steadily gaining popularity.
•First coined by Leigh Van Valen of the University of
Chicago, it refers to Lewis Carroll's Through the Looking
Glass, in which the Red Queen tells Alice, "[I]t takes all
the running you can do, to keep in the same place.”
•This never-ending evolutionary cycle describes many
natural interactions between hosts and disease, or
between predators and prey: As species that live at each
other's expense coevolve, they are engaged in a
constant evolutionary struggle for a survival advantage.
•The cyclical nature of these battles could be the key to
much of the genetic diversity observed in nature.
•The Parasite Red Queen hypothesis for sex is simple:
Sex is needed to fight disease.
•Diseases specialize in breaking into cells, either to eat
them, as fungi and bacteria do, or, like viruses, to
subvert their genetic machinery for the purpose of
making new viruses.
•To do that they use protein molecules that bind to other
molecules on cell surfaces.
•The arms races between parasites and their hosts are
all about these binding proteins. Parasites invent new
keys; hosts change the locks. For if one lock is common
in one generation, the key that fits it will spread like
wildfire. (frequency dependent selection)
•So you can be sure that it is the very lock not to have a
few generations later
•According to the Red Queen hypothesis, sexual
reproduction persists because it enables host species to
evolve new genetic defenses against parasites that
attempt to live off them.
(see Hamilton Symposium
pdf I’ll post tomorrow)
W. D. Hamilton
•Sexual species can call on a "library" of locks
unavailable to asexual species.
•This library is defined by two terms: heterozygosity,
when an organism carries two different forms of a gene
•and polymorphism, when a population contains
multiple forms of a gene. Both are lost when a lineage
becomes inbred
•What is the function of heterozygosity? In the case of
sickle cell anemia, the sickle gene helps to defeat
malaria. So where malaria is common, the
heterozygotes (those with one normal gene and one
sickle gene) are better off than the homozygotes (those
with a pair of normal genes or sickle genes) who will
suffer from malaria or anemia.
•One of the main proponents of the Red Queen
hypothesis was the late W. D. Hamilton.
•In the late 1970s, with the help of two colleagues from
the University of Michigan, Hamilton built a computer
model of sex and disease, a slice of artificial life
•It began with an imaginary population of 200 creatures,
some sexual and some asexual. Death was random. As
expected, the sexual race quickly died out.
•In a game between sex and "asex," asex always wins -other things being equal. That's because asexual
reproduction is easier, and it's guaranteed to pass genes
on to one's offspring.
•Next they introduced several species of parasite, 200 of
each, whose power depended on "virulence genes"
matched by "resistance genes" in the hosts.
•The least resistant hosts and the least virulent parasites
were killed in each generation.
•Now the asexual population no longer had an automatic
advantage -- sex often won the game.
•It won most often if there were lots of genes that
determined resistance and virulence in each creature.
• In the model, as resistance genes that worked would
become more common, then so too would the virulence
genes. Then those resistance genes would grow rare
again, followed by the virulence genes.
•As Hamilton put it, "antiparasite adaptations are in
constant obsolescence.”
•But in contrast to asexual species, the sexual species
retain unfavored genes for future use.
•"The essence of sex in our theory," wrote Hamilton, "is
that it stores genes that are currently bad but have
promise for reuse. It continually tries them in
combination, waiting for the time when the focus of
disadvantage has moved elsewhere."
•A host parasite arms race can make sex
beneficial:
•Hosts resistant to parasite genotype I are
necessarily susceptible to genotype II, and vice
versa.
•As the parasite population evolves in response
to the hosts, it first selects for hosts resistant to
parasite genotype I, then for hosts resistant to
parasite genotype II.
•Genes for sex ride to high frequency in the
currently more-fit genotypes they help create.
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
"Well, in our country," said Alice, still panting a little, "you'd generally get to
somewhere else—if you ran very fast for a long time, as we've been
doing.""A slow sort of country!" said the Queen. "Now, here, you see, it takes
all the running you can do, to keep in the same place. If you want to get
somewhere else, you must run at least twice as fast as that!"
“If the idea about parasites is right, species may be seen in essence as
guilds of genotypes committed to free fair exchange of biochemical
technology for parasite exclusion.” -Bill Hamilton
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Case study II:Sexual selection, parasites and
the Hamilton Zuk hypothesis
•Why is life so colorful?
•Many male birds, for example, have showy colors that
are favored by females
•The colors are status symbols…but of what, exactly?
•Does a male peacock’a tail help it gather food, or avoid
predators?
•It seems a sort of costly way to advertise….
•The high price is actually the key to understanding the
information being communicated
•Impressively adorned males must be the “fittest” of their
kind, capable of investing more energy into their sexual
signals
•Cheap signals invite cheating
•An honest signal must be costly to produce
•Called the Handicap Principle by Amotz Zahavi:
honest signals will be ones that are too pricey to be
acquired by low-quality males, ensuring only the best
males can invest in such signals (flashy sports car,
$5000 suit, etc.)
•But what it meant by “low” and “high” quality males?
•Hamilton and Zuk suggested that bright colors might be
a costly (and honest) signal of a robust immune system
•This links showy sexually selected characteristics with
disease…
•Only males with good genes for parasite resistance
would be in prime condition to express showy colors
•Sick males (“low” quality) will look drab in comparison
•Various false starts: parasite load, testosterone, etc.
•Carotenoids are a family of natural pigments, and are
often the source of bright colors in animals
•The pigments can be stored in various tissues, and are
actually mainly made by plants and algae
•They’re acquired through eating plants or eating other
animals that have eaten plants
•Females finches, guppies, sticklebacks, etc. prefer
males with brighter carotenoid-based coloration
•It turns out that they are costly. They’re used by the
immune system and for detoxification to neutralize free
radicals
•They stimulate the proliferation of T and B lymphocytes
•Scarce carotenoids can either be used for
immunocompetence or showiness and unfit males just
can’t fake it.
•Why is life so colorful?
•Many male birds, for example, have showy colors that
are favored by females
•Hamilton and Zuk suggested that bright colors might be
a costly (and honest) signal of a robust immune system
•Scarce carotenoids can either be used for
immunocompetence or showiness
•Why is life so colorful?
•Many male birds, for example, have showy colors that
are favored by females
•Hamilton and Zuk suggested that bright colors might be
a costly (and honest) signal of a robust immune system
•Scarce carotenoids can either be used for
immunocompetence or showiness
Further reading:
For a readable
introduction to the Red
Queen and its links to
human behavior
Further reading:
For a brilliant synthesis
on the role infectious
disease has played in
the unfolding of world
history.
Further reading:
For some great papers
on the role of parasites
in the evolution of sex
and sexual selection
Further reading:
For a nice introduction
to some of the best
primary literature in
evolutionary biology,
including the Haldane
paper on disease