1. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Chapter 14 Human Origins Why are we humans? Where did we come from? Which monkey is more related to us? Using DNA to understand the beginnings of humankind

2. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Contents  Methods  Comparing great-ape and human DNA  Comparing genetic markers in living humans  Recovering ancient DNA  Insights  Phylogenetic relationships  Time and place of human origins  Prehistoric human migrations  Uncovering past social practices

3. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 The morphometric approach  Compare physical attributes of humans  To living species  To fossil record  Degree of relatedness is determined by physical similarities  Starting point for 19th-century biologists: How closely related are we to existing species?  Speculated that humans and apes shared a recent common ancestor.

4. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 The great apes  Apes have no tails  Great apes  Excludes gibbon, a type of Asian ape  Orangutan is the only great ape that does not live in Africa  Great apes  Share high level of cognitive ability  But have very different social behaviors bonobo orangutan gorilla chimpanzee human Look similar?

5. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Social behaviors of great apes  Gorillas live in harems dominated by a single male, while orangutans lead fairly solitary lives.  Chimpanzee society is marked by a rigid separation of the sexes. Adult males interact with females primarily for the purpose of mating. The males spend the rest of their time in male-only groups that will occasionally wage war against other chimpanzees.  Amazingly, the chimpanzee’s closest ape relative, the bonobo, shows very different behavior. These apes are generally peace-loving and avoid the violence that is typical of the other four members of the great apes. Bonobos relieve stress in their social group by engaging in seemingly random sexual relations. Groups of bonobos consist of both males and females with strong bonds to one another. There are many similarities in great-ape behavior as well.  All great apes appear to be very intelligent. For example, researchers have been able to teach a crude form of sign language to gorillas, chimpanzees, and bonobos.  Experiments have shown that all the great apes are able to recognize themselves in mirrors, an ability that seems absent in the rest of the primate world.  These studies do suggest that the great apes share something very special.

6. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Phylogeny of great apes Based on DNA sequences 13–15 4–6 6–8 OrangutanGorillaHumanChimpanzeeBonobo ~2.6 million years ago

7. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Reduced diversity in humans (Based on 10 Kbp DNA sequence from non-coding region of X chromosomes) humans bonobos chimpanzees gorillas orangutans Closely related so recent diversion From 3,700 individuals 160,000 to 190,000 years ago Less related

8. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 DNA comparisons among great apes DNA/DNA hybridization Great apes Genomewide similarity to humans Human100% Bonobo and Chimpanzee 98.4% ( DNA homology shows 95%) (Protein genes 99% similar) Gorilla97.7% Orangutan96.4%

9. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Differences in gene expression levels among the great apes LiverBloodBrain 1.3-fold5.5-fold1.0-fold Human Chimp Rhesus HumanChimp Rhesus Human Chimp Rhesus A microarray study of 12,000 human genes was used to analyze expression patterns in rhesus monkeys, chimpanzees, and humans. Disparity in cognitive abilities

10. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 The FOXP2 language gene (TF) People with mutations in FOXP2 are unable to articulate properly and have serious grammatical and linguistic deficits.

11. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Looking for positive selection in the human genome  Two types of nucleotide substitutions  Nonsynonymous (d N )  Results in amino acid changes  Synonymous (d S )  No change in amino acid sequence  Null hypothesis  d N = d S  d N / d S < 1  Positive-selection hypothesis  d N / d S > 1  Testing for positive selection  Measure probability (or P-value) that null hypothesis accounts for nucleotide differences in a set of genes

12. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Testing human–chimp–mouse orthologs for positive selection  Human and mouse genomes are fully sequenced  Look for orthologs in databases  Find chimpanzee orthologs by using PCR  Primers from human exonic regions are used  Match resulting 7,645 chimpanzee genes to human and mouse orthologs

13. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Human genes indicating positive selection  Notable categories of genes showing positive selection  Olfaction (Smell)  Amino acid catabolism  Genes involved in Mendelian diseases (OMIM)  Hearing  Neural development  Skeletal development  Homeotic transcription factors (early development)

14. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 The fossil record  Fossils are broadly defined as any evidence of past life  Can be dated by the following methods:  Studying radioactive decay in specimen (C-14)(<50K)  Comparing with other datable material found in the same or similar geological layer  Sometimes cannot date specimen at all  Specimen’s habitat can be deduced from the following information:  Types of fossils found with specimen (Coexistence)  Geological evidence indicative of climate (flora and fauna)

15. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Australopithecines  Australopithecines are earliest hominids (apes)  Lived 1–5 million years ago  Inhabited eastern and southern Africa  Two types  Gracile (e.g., “Lucy”)  Robust  Gracile forms may have been human ancestors “Lucy” A. afarensisH. sapiens

16. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Homo  Modern humans belong to the genus Homo  H. sapiens  Ancestors  H. habilis (2.0–1.6 MYA)  H. ergaster (1.8–0.3 MYA)  H. heidelbergensis (0.4-0.8 MYA)  Dead ends  H. erectus  H. neanderthalis (0.15- 0.3 MYA) 4 3 2 1 0 Million years ago

17. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Homo erectus Homo erectus the species of humans that followed Homo habilis and preceded Homo sapiens in our line of evolution. Homo erectus evolved in East Africa nearly 2 million years ago. They were the first humans to expand their range into Asia and Europe. By at least 400,000 years ago, they were beginning a transitional evolutionary phase that would eventually lead to archaic Homo sapiens.. Homo ergaster An early form of the species Homo erectus from East Africa. In an alternate interpretation, some researchers consider Homo ergaster to be the species that immediately preceded Homo erectus in our line of evolution. Homo ergaster fossils date about 1.8-1.5 million years ago. Homo habilis a transitional species between the australopithecines and Homo erectus. Homo habilis may have first appeared by 2.5-2.4 million years ago and continued until about 1.5 million years ago. They lived in East and possibly South Africa. Homo heidelbergensis A very early form of archaic Homo sapiens in Europe and North Africa that lived from about 800,000 to 200,000 years ago. In an alternate interpretation, some researchers consider Homo heidelbergensis to be a separate species. Homo heidelbergensis may have been the ancestor of the Neandertals. Homo rudolfensis An early form of the species Homo habilis. In an alternate interpretation, some researchers consider Homo rudolfensis to be the species that immediately preceded Homo habilis in our line of evolution. Homo rudolfensis fossils date 2.4-1.9 million years ago. Homo sapiens Our species of humans. Homo sapiens evolved from Homo erectus over several hundred thousand years beginning by at least 400,000 years ago. The first modern Homo sapiens most likely evolved from archaic Homo sapiens by about 200,000-100,000 years ago in Africa and/or Southwest Asia. human a member of the genus Homo. http://anthro.palomar.edu/homo/glossary.htm#hominid

18. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Limitations of fossil record  Complete fossils are very difficult to find  Distribution of fossils may not correlate to range of species  Difficult to estimate duration of species on planet, based on small number of individuals  Differences in morphology cannot be well correlated to genetic differences, which more accurately reflect course of evolution

19. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Sequences unique to the hominid lineage  Yp11 (4 MBP), on Y chromosome found only in humans  Derived from Xq21.3, on X chromosome  Xq21.3 not inactivated, meaning males and females have two functional copies  Xq21.3 and Yp11 contain genes involved in development of nervous system XYY Xq21.3 Yp11

20. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Multiregional evolution vs. “out of Africa” H. erectus H. sapiens H. neanderthalensis H. ergaster H. erectus H. heidelbergensis

21. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Multiregional evolution  Extinct hominids are direct ancestors of modern humans  Neanderthals gave rise to Europeans, H. erectus to Asians, etc.  Extinct hominids interbred  Humans are the product of extensive gene flow between different hominid types H. erectus H. sapiens

22. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 “Out of Africa”  Single-origin hypothesis  Modern humans arose very recently  Modern humans are distinct from other hominids  Neanderthals and H. erectus were not direct ancestors of humans but extinct expts.  Modern humans displaced other groups H. sapiens H. neanderthalensis H. ergaster H. erectus H. heidelbergensis

23. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Mitochondrial Eve (Rebecca Cann et al)  1987: A phylogenetic tree based on mtDNA restriction maps was constructed  12 enzymes used 195 polymorphisms  mtDNA inherited maternally  Deepest node shows one branch exclusively African, the other both African and non-African  Suggests humanity’s maternal ancestor lived in Africa Ancestor Africans Africans & non-Africans

24. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Genomics and mitochondrial Eve Based on 53 mt Sequences (2000) 52,000 ± 27,500 years ago left Africa 171,500 ± 50,000

25. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 The Y chromosome’s story (2001) 163 African and Asian populations The Y chromosome was selected because it does not undergo the process of chromosomal recombination (Nuclear genes?)

26. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 More explanation  All of the Asian individuals used in the study were found to have polymorphisms (YAP, M89, and M130) that could be traced to a single mutation (M168) found in Africa. The M168 mutation was estimated to be only 35,000 to 89,000 years old, thus supporting evidence that modern humans spread from Africa in the last 100,000 years. The phylogenetic tree in the slide shows how the different Y-chromosome haplotypes are related. Red branches represent African-only haplotypes, green branches represent African and Asian haplotypes, and blue branches represent Asian- only haplotypes. The map shows how some of these markers may have spread through Asia. These findings are supported by another study that looked at a greater number (43) of Y-chromosome markers in 50 worldwide populations of men and also found strong evidence for the “out of Africa” hypothesis.

27. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 What happened to the other hominids? Neanderthals, our closest hominid relatives.

28. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Neanderthals HumanNeanderthalHumanNeanderthal 1200–1750 ml1200–1700 ml Hardware for higher cognitive functions was at least present so could they speak? not clear!

29. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 The Neanderthals were sophisticated  Neanderthal culture  Burial of the dead  Tools  Fire  Why did they go extinct?  Absorption into modern human gene pool? Ancestors of Europeans  Replacement by modern humans? Neanderthal tools

30. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Retrieving ancient DNA

31. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Properties of ancient DNA  Postmortem DNA degradation  Endogenous nucleases  Oxidation  Background radiation  Hydrolytic damage  Limits of ancient DNA retrieval  mtDNA almost always used because of multiple copies per cell  Under ideal circumstances, it may be possible to extract DNA as old as 1.0 million years

32. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Analysis of Neanderthal mtDNA human–human human–Neandertal human–chimp Therefore, humans are only distantly related to Neanderthals.

33. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Neanderthal phylogeny (mtDNA)

34. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Human migrations  Hominid species existed in Africa, Europe, and Asia for hundreds of thousands of years, but…  H. sapiens is the first hominid to arrive…  in Australia (60,000 y.a.)  the Americas (18,000–30,000 y.a.)  Polynesia (3,000–1,000 y.a.)  Vast migrations occurred in prehistoric times

35. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 The Cavalli-Sforza approach (1960s and 1970s)(blood proteins and PCA) The spread of agriculture? in Europe Fertile crescent

36. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Using Y chromosomes to uncover European migrations (2000)  1,007 European and Middle Eastern Y chromosomes were genotyped  19 Y-chromosome haplotypes characterize European and Near Eastern men  10 key mutations account for > 95% of European samples  Most European haplotypes dated to before the spread of agriculture

37. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Y-chromosome haplotypes in Europe Mediterranean populations were far more affected by the arrival of migrants from the Middle East than the rest of Europe was Yellow and red associated with agriculture spread

38. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Inferences about European migrations  Haplotypes associated with rise of agriculture account for 22% of European Y chromosomes  Corroborated by mtDNA study  Results match those of original blood-marker study  Models of migration consistent with Y- chromosome data  Two preagriculture migrations  One migration during the rise of agriculture

39. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Populating the Americas  Standard hypothesis  Ancestors of indigenous people arrived via land bridge connecting Alaska to Siberia 13,500 years ago  Archaeological and DNA evidence collected since early 1990s indicates otherwise  Much earlier migration  Possibly 20,000 years ago or earlier  Multiple waves of migrants  Possibly of different ethnic origins  Some may have arrived by boat  More diverse than thought previously

40. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Phylogeny of America’s indigenous people (544 native Americans’ mt DNA) Three language groups Native Americans crossed into North America from Siberia 30-40,000 years ago. This happened twice. Two ways of making trees

41. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Polynesian migrations  Polynesia  Isolated islands scattered across 4,500 km  Last area of world to be colonized by humans  Where did Polynesians come from?  Started their journey 3,000 years ago  Express-train hypothesis: Ancestors of Polynesians began in Taiwan, bypassed adjacent Melanesia for more distant Polynesia  Sequence data from mtDNA of contemporary Polynesians support the express-train

42. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Polynesian Y-chromosome markers These data prompted scientists to adopt the “slow-boat hypothesis,” which states that Austronesian migrants settled in Melanesia, mingled with the local population, and then grew in number before heading for the Polynesian islands.

43. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Insight into ancient social practices from DNA  Inheritance of mtDNA ( maternal) and Y chromosome (paternal) provide separate genetic histories of the sexes  Comparison of mtDNA and Y-chromosome markers can yield insight into marriage and sex practices

44. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Mobility of men vs. women  Who spread their genes over a greater distance, men or women?  Comparison of mtDNA and Y-chromosome genetic markers suggest that women moved farther  Consistent with observation that women in traditional societies leave their homes to be with their husband’s family when they marry

45. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Caveats of using DNA to uncover human origins (disclaimer)  Statistical assumptions vs. biological reality  Intermingling populations create complications  Challenges to the assumption of a steady molecular clock  Genetic drift (small populations isolate)  Selection  Model vs. model-free results  The paucity of data

46. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Summary  The fossil record has uncovered the remains of extinct hominid species  Analysis of human DNA complements, but does not replace, the value of the fossil record  DNA comparisons of humans with other great apes lend insight into what makes humans unique  Analysis of extinct-hominid DNA elucidates our evolutionary past  Genetic comparisons between extant humans reveal ancient origins and behavior

47. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 New slides updated

48. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Paleogenomics  New sequencing technique requires no primers for extraction of ancient DNA  Successfully used to extract 28 million base pairs from woolly mammoth!

49. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Analyzing the ancient DNA  13 million base pairs from mammoth  Nuclear and mitochondrial  98.55% sequence similarity with modern elephant  Remaining DNA  Endogenous micro-organisms  Small amount of human contaminants  Success signals beginning of “paleogenomics”

50. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 First Draft of Chimpanzee Genome  Published September, 2005  3.5X coverage  Comparisons to human genome  Base pair level  Duplications  Deletions  Evidence of selective pressures

51. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Base pair comparisons  Divergence of 1.23%  Agrees with other recent studies  Lowest divergence in X- chromosome  Highest divergence in Y-chromosome Reprinted by permission from Macmillan Publishers Ltd: Nature, (437: 69-87) From Figure 1 in The Chimpanzee Sequencing and Analysis Consortium “Initial sequence of the chimpanzee genome and comparison with the human genome” (2005).

52. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Segmental differences  Magnitude of differences in genomes  Due to base-pair divergence: 1.2%  Due to indels (insertions deletions): 3.0%  Due to segmental duplications: 2.7%  Duplicated complete and partial genes  177 found in human, but not chimpanzee  94 found in chimpanzee, but not human  Duplication rate since divergence  4-5 megabases per million years

53. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Evidence of selection  Estimating the level of positive selection  Examine coding regions  K A : rate of non-synonymous substitutions  K I : rate of synonymous substitutions  Low K A /K I  Strong selective constraints  High K A /K I  Weak selective constraints  Evidence for positive selection  Highest K A /K I genes  Involved in reproduction and immunity

54. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Primate genomes on the horizon  Gorilla  Sequencing begun in October, 2005  Orangutan  Draft sequence expected in 2006  Gibbon (lesser ape)  Some sequencing planned  Rhesus monkey (old world monkey)  Due soon  Marmoset  Draft sequence expected in 2006

55. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Recombination hotspots in humans and chimpanzees  Compare orthologous sequences in human and chimpanzee  Sequence similarity greater than 98%  Linkage disequilibrium (LD) reveals recombination hotspots  Little match between hotspots in human and chimpanzee

56. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Conclusions  Recombination rates change in a way that is disproportionate to the high level of sequence similarity between humans and chimpanzees  How do recombination rates differ when chimpanzee and human sequences are so similar?  Epigenetic effects?  SNP differences between the two species are sufficient to cause different patterns of recombination?

57. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Homo floresiensis  New species of Homo  Found in Indonesia  18,000 years old  Shared planet with H. sapiens  Physical attributes  ~1 meter tall  Small brain  Skeleton like H. erectus From Figure 2 in Mirazon, M and Foley, R (2004) “Palaeoanthropology: Human evolution writ small” Nature 431: 1043-1044.

58. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 The Chimpanzee Genome  Motivation for sequencing  Medical applications  Evolutionary studies  Informative differences  Insertions/Deletions  Difference in regulatory regions  Different genes  SNPs

59. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Progress in sequencing the chimpanzee genome  December 2003  First draft completed  May 2004  Chimpanzee chromosome 22 sequenced to same accuracy as human genome  Chimpanzee chromosome 22 homologous to human chromosome 21  Trisomy 21 in humans results in Down’s syndrome

60. © 2005 Prentice Hall Inc. / A Pearson Education Company / Upper Saddle River, New Jersey 07458 Differences between human and chimpanzee chromosomes  Nucleotide substitutions for 1.4% of sequence  68,000 indels  Range in size: 30 bp to 54,000 bp  Human insertions of ~300 bp due to Alu element  47 protein-encoding genes estimated to have significant structural differences From Figure 1a in The International Chimpanzee Chromosome 22 Consortium (2004) “DNA sequence and comparative analysis of chimpanzee chromosome 22” Nature 429: 382-388.