Lecture 15: Aging and Other Life History Characters

1. Lecture 15: Aging and Other Life History Characters Chapter 13

2. What is life history? • Life histories describe: • Age at maturity (age of 1st reproduction) (early or late) • Reproductive patterns (reproduce once or many times) • Number of offspring (many or few) • Size of offspring (large or small) • Life span (short or long) • Life history is a description of the way in which organisms realize their fitness • “Life history components” are “fitness components”

3. Life histories and trade-offs • Because the amount of energy than an organism can harvest is finite, life histories inevitably involve trade-offs: • many small vs. few large offspring • rapid reproduction and shorter life span vs. slower reproduction and longer life span • Natural selection should attempt to adjust the allocation of energy between growth, metabolism, repair, and reproduction in such a way as to maximize total lifetime reproduction (= fitness)

4. The life history of a hypothetical female Virginia opossum

5. Life history theory attempts to answer questions such as the following: • Why do we age (senesce)? • Why do some species reproduce only once while other reproduce repeatedly? • Why do some species have many small offspring while others have only a few relatively large ones? • Why do some take a long time to reach reproductive maturity, others only a short time?

6. Aging and life span:what is aging? • Mortality senescence Decrease in the probability of survival, per unit time, as age increases • Reproductive senescence Decrease in reproduction with increasing age

7. Survivorship Patterns px is the probability of surviving from age x to x+1

8. Survivorship Patterns px is the probability of surviving from age x to x+1

9. Survivorship Patterns px is the probability of surviving from age x to x+1

10. Mortality Patterns qx is the probability of dying in the age interval x to x+1 (= 1 - px)

11. Aging in collared flycatchers: natural populationNumber of fledged young < after age 3

12. Aging in red deer: natural population males father fewer calves after age 9, but females 13both sexes have very low survivorship after age 13

13. Aging in D. melanogaster: laboratory populationEggs laid by females declines after age 12 daysSurviving drops after 20 days

14. Rate-of-living theory of aging:“live fast, die young” • Aging is caused by accumulation of irreparable damage to cells and tissues • Damage is caused by errors in replication, transcription and translation; and by toxic metabolic by-products (oxidative damage, etc.) • All organisms have been selected to resist and repair cell and tissue damage to the maximum extent physiologically possible. They lack the genetic variation that would enable them to evolve more effective repair mechanisms than they already have.

15. Predictions of the rate-of-living theory of aging • Because cell and tissue damage is caused in part by the by-products of metabolism, the aging rate should be correlated with the metabolic rate, or, equivalently, different species (within broad taxonomic groups) should have similar per gram total lifetime energy expenditures • Because organisms have been selected to resist and repair damage to the maximum extent possible, species should not be able to evolve longer life spans

16. These data suggest that prediction (1) is not upheld Bats, in particular, live almost 3 times longer than other mammals of similar size and metabolic rate Marsupials have significantly lower metabolic rates than other mammals of the same size, but also have significantly shorter life spans

17. Experiments show that prediction (2) is not upheld Life span of D. melanogaster is easily increased by selection in the laboratory. This means that there is heritable genetic variation for life span.

18. The “telomere” theory of aging • Telomeres are tandemly repeated nucleotide sequences that are placed on the ends of eukaryotic chromosomes by the enzyme telomerase (TTAGGG in humans) • Telomeres are necessary because linear chromosomes shorten with each round of replication. Without them, chromosomes would erode away • Telomerase is not expressed in most somatic cells • This means that somatic cells can undergo a limited number of mitotic divisions • Under this theory, individuals age because they can no longer replace damaged and worn-out cells

19. The “telomere” theory of aging Telomere length declines with age in Zebra finches

20. A prediction based on the “telomere” theory of aging • If life span is limited by the number of cell divisions, and different species have similar numbers of cell divisions before telomeres are eroded away, then the life spans of whole organisms should be correlated with the life spans of their constituent cells • So longer lived animals should have longer teleomeres…but this is not true!

21. Life span of cells and whole organisms But, longer-lived mammals have shorter telomeres

22. Short telomeres seem more resistant to oxidative (damaging) stress Long telomere mammals have less resistance to oxidation (fail to halt replication in damaged cells) Trade-off between signs of aging and tumor suppression in mice (p53 is a tumor suppressor in mice)

23. The paradox of aging – 1 • The rate-of-aging and telomerase theories address the physiological, cellular and molecular causes of aging — whether correct or not, they leave an important question unanswered: • If laboratory fruit fly populations can evolve longer life spans, and bats have evolved longer life spans than other mammals of similar size and metabolic rate, and genetic engineers can increase the number of times cells can divide by artificially increasing telomerase expression, why has natural selection not produced longer life spans in all species?

24. The paradox of aging – 2 • All other things being equal, longer life span and high levels of reproduction into late age will equal greater fitness. Given that aging (senescence) reduces individual fitness and given that there is genetic variance for life span, why doesn’t natural selection reduce or eliminate aging? • To answer this question, we need an evolutionary theory of senescence

25. The evolutionary theory of senescence So aging is caused not so much by cell/tissue damage but by failure to completely repair this damage. Upkeep should be easier than manufacture! Failure is caused by either deleterious mutations or trade-offs between repair and repoduction.

26. A verbal argument • Death before reproduction = zero fitness • Death after reproduction begins = greater than zero fitness • Therefore: natural selection will work most effectively against lethal mutations that kill before reproduction begins, but less effectively against lethals that act later in life. • If harmful genetic effects are expressed late enough in life, selection against them will be negligible because most individuals carrying the harmful alleles will already have died from other causes (predation, accident, etc.)

27. A hypothetical non-senescent life history (constant survivorship, constant reproduction for ages ≥ 3, all individuals die before age 16Note that having a gene that causes death at age 14-since most individuals will not survive that long anyway, selection against this is low (versus if it was during early years, before the animal could reproduce much!),

28. Evolutionary genetic mechanisms • Mutation accumulation Peter Medawar (1952) — senescence due to deleterious alleles with effects confined to late ages — senescence evolves because natural selection is powerless to prevent it (many cancers?) • Antagonistic pleiotropy (trade-offs) George Williams (1957) — senescence due to alleles with beneficial effects early in life but deleterious pleiotropic effects late in life —senescence is selectively advantageous (remember breast cancer example!)

29. An implication of the evolutionary analysis • The rate of senescence of an organism should evolve by natural selection in response to environmental changes that alter the schedule of survivorship and fecundity — e.g., if the environmental force of mortality declines so that survivorship to later ages is increased, then selection should favor reduced rates of senescence (and vice versa).

30. Increase in inbreeding depression (loss of genetic diversity) with age is consistent with the mutation accumulation mechanism of senescence10 inbred lines of fruitflies in labAll individuals homozygous at most lociCrossed inbred fliesCrossed some of the inbred flies with other flies, resulted in more heterozygous progenyCompared reproductive success of both kinds of crosses and compared outcrossed flies with the inbred flies---made a calculation based on this (see page 502 for those details).

31. Increase in inbreeding depression with age is consistent with the mutation accumulation mechanism of senescence---inbred lines harbor more deleterious mutations that contribute to senescence

32. Bred flies but limited the days for repoducing to 4 or 5 (short early window for reproduction), then used thopse offspring to establish the next generation. Decrease in life span in houseflies when adults live ≥ 4 days is consistent with mutation accumulation.

33. Late-acting deleterious mutations should be rendered neutral by this experiment (and could drift to high frequency)Neutral evolution is as rapid in small as large populations, so should be similar between the twoMonitored this by allowing some flies to live out their lives in full---later generations die young!

34. Pleiotropy-alleles affect more than one traitAntagonistic pleiotropy in the age-1 gene (hx546 allele) of C. elegans-hx546 worms live longer lives • Frequency of life-extending hx546 allele with no food shortage • Frequency of hx546 allele when occasionally starved

35. Trade off in fruitflies methuselah gene (ww = normal, mw, mm have methuselah allele) • Ww live shorter lives • Ww have more offspring

36. trade-off between early age and later age reproduction in collared flycatchers • Females that reproduce at age 1, have fewer offspring later in life • Females given extra offspring to raise at age 1, lay fewer eggs in subsequent years

37. trade-off between early age and later age reproduction in plants

38. Island opposums vs mainland (mainland have many predators)

39. How many offspring should an individual produce in a given year? • Clutch size in birds and Lack’s hypothesis: Clutch size should be such that it maximizes the number of surviving offspring

40. A mathematical treatment of Lack’s hypothesis • Given the relationship between clutch size and the probability of survival of individual offspring, the clutch size that maximizes the number of surviving offspring is 5

41. Most birds lay smaller clutches than predicted by Lack’s hypothesis Clutch size and number of young per clutch in great tits

42. Reasons why birds may not behave according to Lack’s hypothesis • Lack’s hypothesis assumes that there is no trade-off between reproduction in one year and the next • Lack’s hypothesis assumes that the only effect of clutch size on the offspring is through their survivorship Clutch size of mothers affects clutch size of daughters in collared flycatchers

43. Useful as null model • Parasitoid wasps, similar reasons as in birds to not see the optimal size predicted by Lack.

44. Useful as null model • Parasitoid wasps also can produce multiple clutches quickly, unlike birds. • There is the additional foraging optimization that plays into the wasp’s fitness.

45. How big should offspring be? • Trade-off between size and numbers of offspring • A pie can be sliced into several large pieces or many small ones, similar to few large offspring or numerous smaller ones. • Can see that egg number and size in both fruitflies (A) and fishes (b) are correlated.

46. Maintenance of genetic variation • Natural selection should reduce variability of a trait • Life-history traits are closely correlated with fitness, so we should not see too much genetic variability and that results in less heritability (recent article about this in the news for lifespans in humans!)

47. Maintenance of genetic variation • Can still see some variation though, because different strategies can be beneficial at different times/environmental conditions which can maintain the variation • Some types of reproduction are more fit during certain times of year for sea squirts.

48. Vulnerability to extinction? Clutch sizes in dinosaurs vs. mammals may have allowed for them to persist longer and result in more time to evolve different body sizes