Lecture 3 The central role of parasites in evolution

1. Lecture 3The central role of parasites in evolution

2. The central role of parasites in evolution J.B.S. Haldane (1892-1964)

3. 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.”

4. 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

5. 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 bioticenvironment • -abiotic? • -biotic?

6. 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…”

7. 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?

8. Disease and Evolution, 1949

9. Disease and Evolution, 1949

10. 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

11. Disease and Evolution, 1949 • How do you think infectious disease has impacted the human population through history (and pre-history)?

12. 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

13. 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/grafs/demos/15.html

14. 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

15. 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)

16. 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.”

17. 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?

18. 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?

19. Disease and Evolution, 1949 Given enough time a state of peaceful coexistence eventually becomes established between any host and parasite. -Rene Dubos

20. 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

21. 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.

22. 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.

23. 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.

24. Case study I: Parasites and the advantage of sex Which reproductive mode is better: sexual or asexual? • JMS died recently • Student of Haldane • Aircraft engineer in WWII, came to biology later in life • Leading thinker on the “evolutionary scandal” of sex John Maynard Smith

25. 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?

26. Case study I: Parasites and the advantage of sex Which reproductive mode is better: sexual or asexual? • Null model: (what a null model?) • A female’s reproductive mode does not affect the number of offspring she can make • A female’s reproductive mode does not affect the probability that her offspring will survive (John Maynard Smith, 1978)

27. 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?

28. In a population conforming to JMS’s assumptions, asexual females produce twice as many grandchildren as sexuals, and fraction of asexuals climbs

29. 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!

30. 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…. A female’s reproductive mode does not affect the number of offspring she can make A female’s reproductive mode does not affect the probability that her offspring will survive

31. 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…

32. 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?

33. 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…)

34. 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.

35. 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. 

36. 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)

37. 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. • W. D. Hamilton • (see Hamilton Symposium pdf I’ll post tomorrow)

38. 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.  

39. 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.

40. 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.

41.   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."

42. 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.

45. "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!"

46. “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

47. Case study II:Sexual selection, parasites and the Hamilton Zuk hypothesis

48. 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? 

49. 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

50. 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?