The Human Genome and Human Evolution Y Chromosome

1. The Human Genome and Human EvolutionY Chromosome Dr Derakhshandeh, PhD

2. Outline • Information from fossils and archaeology • Neutral (or assumed-to-be-neutral) genetic markers • Classical markers • Y chromosome • Genes under selection • Balancing selection: • Balancing selection can arise by the heterozygotes having a selective advantage, as in the case of sickle cell anemia • It can also arise in cases where rare alleles have a selective advantage • Positive selection

3. Why Y? • "Adam passed a copy of his Y chromosome to his sons • The Y chromosome is paternally inherited • the Y chromosome a father passes to his son is, in large measure, an unchanged copy of his own

5. But small changes (called polymorphisms) do occur • passed down from generation to generation

6. CHROMOSOME CHANGES • indels • insertions into or deletions of the DNA at particular locations on the chromosome • YAP • which stands for ”Y chromosome alu polymorphism” • Alu is a sequence of approximately 300 letters (base pairs) which has inserted itself into a particular region of the DNA

7. Snips • "single nucleotide polymorphisms“ • Stable indels and snips are relatively rare • so infrequent • they have occurred at any particular position in the genome only once in the course of human evolution • Snips and stable alus have been termed "unique event polymorphisms" (UEPs)

8. microsatellites • short sequences of nucleotides (such as GATA) • repeated over and over again a variable number of times in tandem • The specific number of repeats in a particular variant (or allele) usually remains unchanged from generation to generation • but changes do sometimes occur and the number of repeats may increase or decrease

9. increases or decreases in the number of repeats take place in single steps • for instance from nine repeats to ten • whether decreases in number are as common as increases has not been established

10. Changes in microsatellite length occur much more frequently than new UEPs arise • while we can reasonably assume that a UEP has arisen only once • the number of repeat units in a microsatellite may have changed many times along a paternal lineage

11. The microsatellite data • can facilitate the estimation of population divergence times • which can then be compared (and contrasted) with estimated mutational ages of the polymorphic markers • the combination of these two kinds of data: • offers a powerful tool with which to assess patterns of migration, admixture, and ancestry

12. minisatellites • 10-60 base pairs long • the number of repeats often extends to several dozen • Changes during the copying process take place more frequently in minisatellites than in microsatellites

13. the evolutionary clock • the UEPs as the hour hand • the microsatellite polymorphisms as the minute hand • the minisatellites as a sweep second hand

14. a further benefit of using “Y chromosome” to study evolution • most of the Y chromosome does not exchange DNA with a partner • all the markers are joined one to another along its entire length • linkage of markers

15. The human Y chromosome • can also be used to draw evolutionary trees • the relationships of the Y chromosomes of other primates • The different polymorphic loci are distinguished from each other by their chain lengths • it can be measured using an automatic DNA sequencer

16. Gene scan output of microsatellite DNA analysis from a single individual The microsatellite peaks are sorted by size, the different colors representing different microsatellites. The small red peaks are size markers

17. new UEP arises in a certain man • As the new UEP is copied from generation to generation • The UEP does not change but, albeit not very often: • increasing • decreasing in length • The longer the time since the UEP arose • the greater will be the number of different UEP allele

18. Such a process: • differentiates one population from another • the more closely two populations • display common haplotype frequencies • the more closely related is their biological history likely to be

19. IN ANCIENT TIMES • only the analysis of DNA obtained from our contemporaries • suggested ways in which we might deduce past history from an interpretation of those data: • DNA can be extracted from ancient remains

20. amelogenin gene • exists in two forms: • the one on the X chromosome being different in length from the one on Y • Small portions of: • cranial bones • and teeth • were crushed to powder and decalcified

21. The amelogenin gene • is a single copy gene • homologues of which are located on: • Xp22.1-Xp22.3 • and Yp 11.2

22. DNA was purified • copied by PCR using primers flanking the region • the size of the products was measured by agarose gel electrophoresis • Since Y chromosomes yield fragments 218 base pairs long • while X chromosome products contain 330 base pairs • they should be clearly distinguishable: • if the specimen yields the shorter gene, it must come from a Y chromosome fragment and thus from a male.

23. Disadvantages • DNA is often degraded • so that continuous fragments are no longer present • cannot be copied • substances may be present: • inhibit both purification and amplification

24. The first two human Y chromosome marker • studies appeared in 1985 (Casanova et al. 1985; Lucotte and Ngo 1985) • It was not until almost a decade later that Torroni and co-workers (1994a) published the first Y chromosome data on Native Americans • Numerous surveys of variation on the non-recombining portion of the Y chromosome (NRY) devoted primarily to Amerind speakers quickly followed

25. Who are our closest living relatives? Chen FC & Li WH (2001) Am. J. Hum. Genet.68 444-456

26. Phenotypic differences between humans and other apes * *development of an individual from the moment the egg is fertilized up till adulthood Carroll (2003) Nature422, 849-857

27. Chimpanzee-human divergence 6-8 million years Hominids or hominins Chimpanzees Humans

28. Origins of hominids • Sahelanthropus tchadensis • Chad (Central Africa) • Dated to 6 – 7 million years ago • Posture uncertain, but slightly later hominids were bipedal ‘Toumai’, Chad, 6-7 MYA Brunet et al. (2002) Nature418, 145-151

29. Hominid fossil summary Found only in Africa Found both in Africa and outside, or only outside Africa

30. Origins of the genus Homo • Homo erectus/ergaster ~1.9 million years ago in Africa • Use of stone tools • H. erectus in Java ~1.8 million years ago Nariokatome boy, Kenya, ~1.6 MYA

31. Additional migrations out of Africa • First known Europeans date to ~800 KYA • Ascribed to H. heidelbergensis Atapueca 5, Spain, ~300 KYA

32. Origins of modern humans (1) • Anatomicallymodern humans in Africa ~130 KYA • In Israel by ~90 KYA Omo I, Ethiopia, ~130 KYA

33. Origins of modern humans (2) • Modern human behaviourstarts to develop in Africa after ~80 KYA • By ~50 KYA, features such as complex tools and long-distance trading are established in Africa The first art? Inscribed ochre, South Africa, ~77 KYA

34. Expansions of fully modern humans • Two expansions: • Middle Stone Age technology in Australia ~50 KYA • Upper Palaeolithic technology in Israel ~47 KYA Lake Mungo 3, Australia, ~40 KYA

35. the Upper Paleolithic period • In the Upper Paleolithic period: • Neanderthal man disappears • and is replaced by a variety of Homo sapiens

36. Routes of migration?archaeological evidence Upper Paleolithic ~130 KYA Middle Stone Age

37. Strengths and weaknesses of the fossil/archaeological records • Major source of information for most of the time period • Only source for extinct species • Dates can be reliable and precise • need suitable material, C calibration required 14

38. Mixing or replacement?

39. Human genetic diversity is low

40. Human genetic diversity is evenly distributed Most variation between populations Most variation within populations Templeton (1999) Am. J. Anthropol.100, 632-650

41. Phylogenetic trees commonly indicate a recent origin in Africa Y chromosome

42. Modern human mtDNA is distinct from Neanderthal mtDNA Krings et al. (1997) Cell90, 19-30

43. Classical marker studies Based on 120 protein-coding genes in 1,915 populations Cavalli-Sforza & Feldman (2003) Nature Genet.33, 266-275

44. Phylogeographic studies • Analysis of the geographical distributions of lineages within a phylogeny • Nodes or mutations within the phylogeny may be dated • Extensive studies of mtDNA and the Y chromosome

45. Phylogenetic trees commonly indicate a recent origin in Africa Y chromosome

46. Y haplogroup distribution Jobling & Tyler-Smith (2003) Nature Rev. Genet.4, 598-612

50. An African origin