The Human Genome and Human Evolution Chris Tyler-Smith The Wellcome Trust Sanger InstituteSlide 2
Outline Information from fossils and paleontology Neutral (or thought to-be-unbiased) hereditary markers Classical markers Y chromosome Demographic changes Genes under choice Balancing determination Positive choiceSlide 3
Who are our nearest living relatives? Chen FC & Li WH (2001) Am. J. Murmur. Genet. 68 444-456Slide 4
Phenotypic contrasts in the middle of people and different gorillas Carroll (2003) Nature 422 , 849-857Slide 5
Chimpanzee-human disparity 6-8 million years Hominids or hominins Chimpanzees HumansSlide 6
Origins of primates Sahelanthropus tchadensis Chad (Central Africa) Dated to 6 â 7 million years prior Posture questionable, yet marginally later primates were bipedal âToumaiâ, Chad, 6-7 MYA Brunet et al. (2002) Nature 418 , 145-151Slide 7
Hominid fossil outline Found just in Africa Found both in Africa and outside, or just outside AfricaSlide 8
Origins of the family Homo erectus/ergaster ~1.9 million years prior in Africa Use of stone apparatuses H. erectus in Java ~1.8 million years prior Nariokatome kid, Kenya, ~1.6 MYASlide 9
Additional movements out of Africa First known Europeans date to ~800 KYA Ascribed to H. heidelbergensis Atapueca 5, Spain, ~300 KYASlide 10
Origins of current people (1) Anatomically present day people in Africa ~130 KYA In Israel by ~90 KYA Not colossally fruitful Omo I, Ethiopia, ~130 KYASlide 11
Origins of cutting edge people (2) Modern human conduct begins to create in Africa after ~80 KYA By ~50 KYA, elements, for example, complex apparatuses and long-separation exchanging are set up in Africa The first craftsmanship? Engraved ochre, South Africa, ~77 KYASlide 12
Expansions of completely cutting edge people Two extensions: Middle Stone Age innovation in Australia ~50 KYA Upper Paleolithic innovation in Israel ~47 KYA Lake Mungo 3, Australia, ~40 KYASlide 13
Routes of relocation? archeological proof Upper Paleolithic ~130 KYA Middle Stone AgeSlide 14
Strengths and shortcomings of the fossil/archeological records Major wellspring of data for more often than not period Only hotspot for wiped out species Dates can be dependable and exact need suitable material, C adjustment needed Did they leave relatives? 14Slide 15
Mixing or substitution?Slide 16
Human hereditary differences is lowSlide 17
Human hereditary assorted qualities is equally appropriated Most variety between populaces Most variety inside of populaces Templeton (1999) Am. J. Anthropol. 100 , 632-650Slide 18
Phylogenetic trees usually show a late starting point in Africa Y chromosomeSlide 19
Modern human mtDNA is unmistakable from Neanderthal mtDNA Krings et al . (1997) Cell 90 , 19-30Slide 20
Classical marker studies Based on 120 protein-coding qualities in 1,915 populaces Cavalli-Sforza & Feldman (2003) Nature Genet. 33 , 266-275Slide 21
Phylogeographic studies Analysis of the land disseminations of genealogies inside of a phylogeny Nodes or transformations inside of the phylogeny may be dated Extensive investigations of mtDNA and the Y chromosomeSlide 22
Y haplogroup circulation Jobling & Tyler-Smith (2003) Nature Rev. Genet. 4 , 598-612Slide 23
An African inceptionSlide 24
SE Y haplogroupsSlide 25
NW Y haplogroupsSlide 26
Did both movements leave relatives? General SE/NW hereditary qualification fits two-movement model Basic hereditary example built up by starting colonization All people outside Africa offer same subset of African differences (e.g. Y: M168, mtDNA: L3) Large-scale substitution, or relocations were not free How much consequent change?Slide 27
Fluctuations in atmosphere Ice ages Antarctic ice center information Greenland ice center informationSlide 28
Possible purposes behind hereditary change Adaptation to new situations Food creation â new eating methodologies Population increment â new infectionsSlide 29
Debate about the Paleolithic-Neolithic move Major changes in nourishment generation, way of life, innovation, populace thickness Were these for the most part because of development of individuals or development of thoughts? Solid spotlight on EuropeSlide 30
Estimates of the Neolithic Y commitment in Europe ~22% (=Eu4, 9, 10, 11); Semino et al . (2000) Science 290 , 1155-1159 >70% (expecting Basques = Paleolithic and Turks/Lebanese/Syrians = Neolithic populaces); Chikhi et al. (2002) Proc. Natl. Acad. Sci. USA 99 , 11008-11013Slide 31
More late reshaping of assorted qualities âStar clusterâ Y haplotype began in/close Mongolia ~1,000 (700-1,300) years prior Now conveyed by ~8% of men in Central/East Asia, ~0.5% of men overall Suggested relationship with Genghis Khan Zerjal et al. (2003) Am. J. Murmur. Genet . 72 , 717-721Slide 32
Is the Y an unbiased marker? Intermittent fractional erasures of a locale needed for spermatogenesis Possible negative determination on various (14/43) genealogies Repping et al . (2003) Nature Genet . 35 , 247-251Slide 33
Demographic changes Population has extended in extent and numbers Genetic effect, e.g. overwhelmingly negative estimations of Tajimaâs D Most information not predictable with straightforward models e.g. consistent size took after by exponential developmentSlide 34
Selection in the human genome time Negative (Purifying, Background) Positive (Directional) Neutral Balancing Bamshad & Wooding (2003) Nature Rev. Genet. 4 , 99-111Slide 35
The Prion protein quality and human malady Prion protein quality PRNP connected to âprotein-onlyâ infections e.g. CJD, kuru A typical polymorphism, M129V, impacts the course of these maladies: the MV heterozygous genotype is defensive Kuru procured from custom human flesh consumption was accounted for (1950s) in the Fore individuals of Papua New Guinea, where it brought on up to 1% yearly mortality Departure from Hardy-Weinberg harmony for the M129V polymorphism is found in Fore ladies more than 50 (23/30 heterozygotes, P = 0.01)Slide 36
Non-nonpartisan advancement at PRNP McDonald-Kreitman test Resequence coding district in ? people and primates N S Diversity 5 1 Divergence (Gibbon) 2 13 P - esteem = 0.0055 Mead et al. (2003) Science 300 , 640-643 âcodingâ ânon-codingâSlide 37
Observed Expected Balancing choice at PRNP Excess of middle of the road recurrence SNPs: e.g. Tajimaâs D = +2.98 (Fore), +3.80 (CEPH families) Deep division between the M and V ancestries, assessed at 500,000 years (utilizing 5 MY chimp-human split) 24 SNPs in 4.7 kb district, 95 haplotypesSlide 38
Effect of positive determination Neutral Selection Derived allele of SNPSlide 39
What changes do we anticipate? New qualities Changes in amino-corrosive grouping Changes in quality expression (e.g. level, timing or area) Changes in duplicate numberSlide 40
How would we discover such changes? Chance Ï hHaA sort I hair keratin quality inactivation in people Identify phenotypic changes, examine hereditary premise Identify hereditary changes, research utilitarian outcomesSlide 41
Inheritance of a dialect/discourse deformity in the KE family Autosomal predominant legacy design Lai et al . (2000) Am. J. Murmur. Genet . 67 , 357-367Slide 42
Mutation and development of the FOXP2 quality Chr 7 7q31 Nucleotide substitutions FOXP2 quality noiseless substitution Enard et al . (2002) Nature 418 , 869-872Slide 43
Positive determination at the FOXP2 quality Resequence ~14 kb of DNA contiguous the amino-corrosive changes in 20 various people, two chimpanzees and one orang-utan No lessening in differences Excess of low-recurrence alleles (Tajimaâs D = - 2.20) Excess of high-recurrence inferred alleles (Fay & Wuâs H =-12.24) Simulations recommend a specific compass at (0 â 200,000) years Constant rate of amino-corrosive substitutions? Positive choice in people? substitution (non-synonymous) d N quiet (synonymous) d S Orang Gorilla Chimp Human-particular increment in d N/d S proportion (P<0.001) Enard et al . (2002) Nature 418 , 869-872Slide 44
A quality influencing mind measure Microcephaly (MCPH) Small (~430 cc v ~1,400 cc) however generally ~normal cerebrum, just gentle mental hindrance MCPH5 demonstrates Mendelian autosomal latent legacy Due to loss of action of the ASMP quality ASPM-/ASPM-control Bond et al. (2002) Nature Genet . 32 , 316-320Slide 45
Evolution of the ASPM quality (1) Summary d N/d S qualities Sliding-window d N/d S examination 0.62 0.52 0.53 1.44 0.56 Orang Gorilla Chimp Human-particular increment in d N/d S proportion (P<0.03) Evans et al. (2004) Hum. Mol. Genet. 13 , 489-494Slide 46
Evolution of the ASPM quality (2) McDonald-Kreitman test Sequence ASPM coding locale from 40 differing people and one chimpanzee N S Diversity 6 10 Divergence 19 7 P - esteem = 0.025 Evans et al. (2004) Hum. Mol. Genet. 13 , 489-494Slide 47
asp Microtubules DNA do Carmo Avides and Glover (1999) Science 283 , 1773-1735 What changes? FOXP2 is an individual from an extensive group of interpretation elements and could in this manner impact the declaration of a wide mixed bag of qualities The Drosophila homolog of ASPM codes for a microtubule-tying protein that impacts axle introduction and the quantity of neurons Subtle changes to the capacity of very much monitored qualitiesSlide 48
broad quest for protein arrangement advancement 7645 human-chimp-mouse quality trios analyzed Most noteworthy classifications indicating positive determination include: Olfaction: feeling of smell Amino-corrosive digestion system: diet Development: e.g. skeletal Hearing: for discourse observation Clark et al. (2003) Science 302 , 1960-1963Slide 49
Increased expression Decreased expression Gene expression contrasts in human and chimpanzee cerebral cortex Affymetrix oligonuclotide cluster (~10,000) qualities 91 show human-particular
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