This is a copy of the plenary lecture at the First meeting of the Chilean Society of Evolutionary Biology, Pucon 2007

1. THE MOST IMPORTANT THEORY IN BIOLOGY Douglas J. Futuyma Department of Ecology and Evolution State University of New York Stony Brook, NY November 2007

2. THEORY -- NOT a mere speculation! -- A statement of well-supported general laws, principles or causes of something known or observed -- Usually a complex of statements that together explain many phenomena. -- A term of honor.

4. In each great region of the world the living mammals are closely related to the extinct species of the same region. It is therefore probable that Africa was formerly inhabited by extinct apes closely allied to the gorilla and chimpanzee; and as these two species are now man’s nearest allies, it is somewhat more probable that our early progenitors lived on the African continent than elsewhere. Charles Darwin, 1871 The Descent of Man Scientific theories enable prediction

5. Australopithecus afarensis , ca. 3.5 million years Ethiopia

7. Genetic divergence between organisms increases with time since common ancestor

8. Some mutations alter amino acids in proteins – but not all mutations do so

9. MULTIPLE POPULATIONS, EACH UNDERGOING GENETIC DRIFT Random fluctuations in frequency of alleles that have little or no effect on fitness. Allele frequencies in replicate populations fluctuate independently, eventually reach 0 or 1.0.

10. Natural selection IS a consistent difference in the rate of increase of different genotypes or genes ( and no more than that)

11. Elementary evolutionary event is change in proportions (frequencies) of alleles in a population. These graphs show increase in frequency of one type of chromosome over generations of fruit flies in several lab populations.

12. Rapid adaptation by natural selection: Copper tolerance has evolved in Mimulus guttatus near copper mines

13. Sexual selection results in features that Increase reproductive success.

14. Selection on several functionally interrelated features results in complex adaptations. Adaptations may look as if they have been “ designed.”

15. But how do we explain the poinsettia ( Euphorbia pulcherrima )?

16. But how do we explain the dandelion ( Taraxacum officinale )? Natural selection lacks foresight! Bright flowers look “ designed” to attract pollinators, but pollen is sterile, reproduction is asexual Explicable only as a consequence of evolutionary history

17. Red blood cells from person with “normal” hemoglobin and with sickle-cell hemoglobin Heterozygotes are anemic but resistant to malaria. Homozygotes have sickle cell disease and usually die young.

18. Infanticide Siblicide Natural selection lacks morality. Nature is not a model for ethics. Adaptations Produced by Natural Selection

19. Evolutionary theory makes predictions about phenomena throughout biology. Evolutionary theory explains morphological, behavioral, physiological, genomic characteristics Evolutionary theory explains phenomena that make no sense unless they are results of a blind, impersonal, historical process Evolutionary theory provides cautions against looking to nature for standards of morality or ethics (the “naturalistic fallacy”).

20. THEORY -- NOT a mere speculation!! -- A statement of well-supported general laws, principles, or causes of something known or observed. -- Usually a complex of statements that together explain many phenomena. -- A term of honor. EVOLUTIONARY BIOLOGY IS USEFUL! E.g., Pest management Food production Health Human genetics and genomics Natural resource management (fisheries, forest resources) Discovery of useful natural products Environment and conservation See Evolution, Science, and Society at www.amnat.org

21. Evolutionary biology and food production Finding resistance genes

22. Biological control of weeds

23. Climbing fern, invasive in Florida Everglades Can the mite Floracarus perrerae control it? Mite most effectively attacks fern from same region, so knowing source of invasive fern is important.

24. N. Ellstrand 2003. Phil. Trans. Royal Soc. Lond. B 358:1163 HYBRIDIZATION AND GENE FLOW MAY OCCUR FROM CROPS TO WILD PLANTS Knowing evolutionary relationships among plants specifies wild species that may be at greatest risk of acquiring transgenes from GM crops.

26. (A) Functionally diverse genes are composed of mixtures of modules, largely due to exon shuffling (B) Distantly related animals (fly, nematode worm, human) have many of the same modules.

27. Top: Eye developed in abnormal site due to insertion of an extra Drosophila Pax-6 gene Bottom: Eyes developed in abnormal site due to insertion of human Pax-6 gene Insects and humans have functionally equivalent versions of the major gene that controls eye development.

28. a , Distribution of divergence of the autosomes (blue), the X chromosome (red) and the Y chromosome (green). b , Distribution of variation by chromosome FIGURE 1. Human-chimpanzee divergence in 1-Mb segments across the genome. From the following article: Initial sequence of the chimpanzee genome and comparison with the human genome The Chimpanzee Sequencing and Analysis Consortium Nature 437, 69-87 (1 September 2005) doi: 10.1038/nature04072

29. Mutations in genes that have important functions are likely to disrupt function, to reduce fitness, and to be eliminated from the population by natural selection. Therefore they should evolve slowly. As this theory predicts, genes that have diverged slowly between human and chimpanzee are more likely to cause disease when mutated. Sequence comparisons may therefore reveal other genes of medical importance. Bustamante et al. 2005, Nature 437:1153.

30. FINDING FUNCTIONALLY IMPORTANT SEQUENCES IN THE HUMAN GENOME Such sequences evolve slowly (are “conserved”) because most mutations impair function and are eliminated by natural selection. MCSs, Multispecies Conserved Sequences, are very similar among many species, including distantly related to human. Upper: Conserved human sequences found by match to various species and to All together. Note: more in noncoding regions (green) than in coding regions (yellow). Lower: Example of a noncoding region so found. EH Margulies et al. 2003. Genome Research.

31. Infectious disease evolution of antibiotic resistance

33. Infectious disease evolution of antibiotic resistance tracing origin and spread of disease

34. Phylogenetic analysis of HIV shows multiple spread from chimpanzee to humans

35. Nothing in biology makes sense except in the light of evolution. Theodosius Dobzhansky There are many generalizations in biology, but precious few theories. Among these, the theory of evolution is by far the most important, because it draws together from the most varied sources a mass of observations which would otherwise remain isolated; it unites all the disciplines concerned with living beings; it provides a causal explanation of the living world and its heterogeneity. Fran ç ois Jacob

42. Zygon Volume 39, Issue 3 Page 659 - September 2004 Was Thomas Aquinas a Sociobiologist? Thomistic Natural Law, Rational Goods, and Sociobiology by Craig A. Boyd 1 Journal of Organizational Behavior Volume 27, Issue 2 , Pages 111 - 119 a Special Issue: Darwinian Perspectives on Behavior in Organizations . Darwinism: new paradigm for organizational behavior? The evolution of human homosexual behavior (1). R. C. Kirkpatrick. Current Anthropology 41:385 (June 2000) by Craig A. Boyd 1 Was Thomas Aquinas a Sociobiologist? Thomistic Natural Law, Rational Goods, and Sociobiology Volume 39 Issue 3 Zygon Volume 39 Page 659 - September 2004 doi:10.1111/j.1467-9744.2004.t01-1-00607.x

43. AC Brault et al. 2007, Nature Genetics 39:1162

44. EH Margulies et al. 2003, Genome Research 13::2507-18

45. THEORY -- NOT a mere speculation!! -- A statement of well-supported general laws, principles, or causes of something known or observed. -- Usually a complex of statements that together explain many phenomena. -- A term of honor.

48. Analysis of variation in DNA sequence of a gene among humans can tell us if the gene has been strongly affected by natural selection: Positive selection: an advantageous allele has increased in a population Negative selection: Mutations that affect protein function have been continually purged (showing that the protein has a consistent and important function).

49. Positive selection on human genes in last 10,000 years Suggests adaptation to new environmental conditions taste and smell reproduction carb metabolism Also: lactose metabolism skin pigmentation hair formation Voight et al. 2006. PLoS Biology 4:e72

51. EVOLUTION BY POSITIVE NATURAL SELECTION IN VIRUSES DEPENDS ON TRANSMISSION MODE Selection indicated by high values of dn/dS (amino acid-changing nucleotide substitutions/synonymous substitutions). Significantly high dN/dS much more frequent in genes for surface proteins of non-vector-borne than vector-borne viruses. Suggests conflict between adaptation to human immune system and insect vector’s immune system. May help in design of vaccines and antiviral agents. CH Woelk and EC Holmes, 2002. Mol. Biol. Evol. 19:2333.

52. FIGURE 2. Conservation of synteny between human and mouse. Initial sequencing and comparative analysis of the mouse genome Mouse Genome Sequencing Consortium Nature 420, 520-562 (5 December 2002) doi: 10.1038/nature01262 We detected 558,000 highly conserved, reciprocally unique landmarks within the mouse and human genomes, which can be joined into conserved syntenic segments and blocks (defined in text). A typical 510-kb segment of mouse chromosome 12 that shares common ancestry with a 600-kb section of human chromosome 14 is shown. Blue lines connect the reciprocal unique matches in the two genomes. The cyan bars represent sequence coverage in each of the two genomes for the regions. In general, the landmarks in the mouse genome are more closely spaced, reflecting the 14% smaller overall genome size.

53. Infectious disease evolution of antibiotic resistance tracing origin and spread of disease evolution of virulence

54. JK Taubenberger et al. 2005, Nature 437-889 FLU EPIDEMICS PAST AND PRESENT ‘ Spanish” pandemic (1918) and the 1957 and 1968 epidemics are relatd to and derived from avian influenza strains. 1918, 1957, and 1968 strains all differ from avian strains by 10 amino acids, in the 3 proteins. These are thought to confer adaptation to human host, although probably reducing adaptation to avian hosts. Most of these amino acid substitutions are also found in recent, pathogenic “bird flu,” strain H5N1

56. Are sexually selected features necessary for survival?

57. Natural selection can result in adaptation to an environment.

58. Gorilla Pan Homo … but … but Homo and Pan are actually most closely related. Morphology of Homo has evolved faster than morphology of Pan since their common ancestor.

59. t Tt T t t t t t t + Tt tt tt tt tt tt tt Mouse T-locus: Meiotic drive sperms Eggs (male) offspring Heterozygous male tt males are lethal or sterile!!

60. a , Evolutionary tree. The branch lengths are proportional to the absolute rates of amino acid divergence. b , Maximum-likelihood estimates of the rates of evolution in protein-coding genes for humans, chimpanzees, mice and rats. FIGURE 9. Human−chimpanzee−mouse−rat tree with branch-specific K A/ K S ( ) values.

62. IGF2 IGF2R IGF2 IGF2R IGF2R (IGF2R) (IGF2) IGF2 Egg Sperm Embryo Only paternal IGF2 gene is expressed; increases embryo’s uptake of nutrients from mother through placenta. Only maternal IGF2R gene is expressed; degrades IGF2, reducing embryo’s uptake of nutrients from mom, who defends herself against her baby! GENETIC CONFLICT IN MAMMALS

63. Emsion et al. 2005, Nature 434:857-863