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lec 1 Exodus+of+Early+Man_2012

lec 1 Exodus+of+Early+Man_2012 - PCB4522 Molecular Genetics...

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Unformatted text preview: PCB4522 Molecular Genetics Spring semester 2012 The official course website will be with Sakai e-learning. Use the following to login: http://lss.at.ufl.edu/ Do trees know they are alive? What is an organism? Do bacteria have species? Do bacteria live forever? What is an species? Ring species Ring species Geographical distribution of a ring species. When do two species become distinct? Species gradations as a function of time. When did Homo sapiens become a species? What is the origin of eukaryotes? TBP The origins of our gene expression can be traced back to early life forms... ....cows that burp in the night. DNA TFIIB Archaeal transcriptional apparatus Enough already! Dr. Gurley, get real! The History of Man is written in DNA. Just hanging out. No jobs... tools had not been invented. Australopithecine Nicholas Wade (2006) Before the Dawn. Penguin Press, New York pp. 312. Kenneth Miller (19991) Finding Darwin's God. Harper Perennial, New York pp. 338. How much of human culture is genetic phenotype? Tool making advanced in stages corresponding to large scale changes in genetic makeup. 50,000 200,000 Homo ergaster 1,450,000 800,000 Homo habilis Chrome magnum Cro magnum 50,000 200,000 Neanderthals 1,450,000 800,000 Homo erectus The Earth was only populated by archaic humans until ~100,000 yrs ago. The result of the "first exodus from Africa." Brain size gradually increased: 500,000 yrs ago brain size increased significantly. 200,000 yrs ago it reached modern levels. Ancestors to modern man Archaic humans Homo erectus (Asia) Three human species 50,000 yrs ago. The "first Exodus" probably started around two million years ago by Homo erectus and later by Neanderthals. Homo neanderthalis (Europe/Middle East) When did man become anatomically modern? (What is meant by "anatomically modern?) Answer: More than 500,000 years ago. Anatomically Modern: Before the split between Homo sapiens and the Neanderthals, when the larynx descended so that it was no longer possible to breath and swallow at the same time. Archaic humans were anatomically modern, but not behaviorally modern. The second exit from Africa was ~50,000 yrs ago. Ocean levels were ~200 ft. lower than today due to glaciation. Genetic evidence indicates that a bottleneck occurred reducing the population of modern humans to around 5,000 persons. Only ~150 of these managed to break 715Africa in a single exodus. The southern route to Sahul (Australia) Modern humans reached the Middle East at least 100,000 years ago and Australia about 40,000 yrs ago. Highly branched tree evidence of rapid increase in population size. Y-chromosome Male lineage Mitochondria Female lineage Remnant populations of the ancestral population of 5,000 Andaman Islanders !Kung San Australian Aborigines The Early Migration of humans out of Africa to colonize planet Earth The National Geographic Genographic Project https://genographic.nationalgeographic.com/genographic/index.html There seems to have been a series of mutations in the brain that gave ancestors of modern humans an edge over the archaic humans who blocked the exits out of Africa. ...These resulted in the capacity for highly developed language. The story of FOXP2. Archeologists believe that the appearance of art correlates with the development of complex language. FOXP2 phenotype? Brain of the bonobo (related to chimps) overlaid onto the human brain: red and yellow areas had to be stretched, blue areas are same size. Broca's area is one of those in red. Imitation Imitation (red) (red) Language area (Broca's and Wemicke's) in yellow--overlap (orange) with areas critical for imitations (red). Anatomically modern humans since about 500,000 yrs ago. Language Language (yellow) (yellow) Chimps gesture with both face and hands Holden (2004) The origin of speech. Sci. 303:1316-1319. FoxP2 transcription factor The FoxP2 gene has 715 amino acids. The comparisons of nonsynonymous and synonymous nucleotide substitutions indicate that these mutations have been highly selected within the last 200,000+ yrs. (1/2 = 1 nonsynonymous and 2 synonymous mutations in the interval) Were mutations in FOXP2 Were mutations success of responsible for thein FOXP2 responsible vs. Neanderthals? Homo sapiensfor the success of Homo sapiens vs. Neanderthals? The FOXP2 gene is ancient in origin and highly conserved. Chimpanzees and gorillas carry the identical version which must be the same one carried by the common ancestor to Chimps and humans 5 million yrs ago. The Chimp/gorilla version only differs by a single amino acid from that present in mice. In the 65 million yrs separating chimps and mice, there was only a single mutation; however, in the 5-7 million yrs since humans split from chimps, two mutations have occurred. The Derived FOXP2 Variant of Modern Humans Was Shared with Neandertals Krause et al. (2007) Current Biol. 17:19081912 Zhang, Webb and Podlaha (2002) Accelerated Protein Evolution and Origins of Human-Specific Features: FOXP2 an exmple. Genetics 162: 1825-1835. Non-African populations of modern humans contain 1-4% Neanderthal DNA Vindija Neanderthal contribution Samples and sites from which DNA was retrieved (finger bones). R E Green et al. Science 2010;328:710722 Four possible ways Neanderthal DNA could have entered modern humans. Route 3 is most likely. Denisova Homo erectus Denisova Homo erectus contribution contribution Denisova cave Siberia 80,00 yr ago 660,000 140,000 Reconstruction of Neanderthal female Evidence for a Evidence for a second Neanderthal second Neanderthal gene flow into some gene flow into some modern humans. modern humans. Melanesians have from 4-6% of genome from Neanderthal. D Reich et al. Nature 2010; 468:1053-1060 When did man become behaviorally modern? Answer: Comparisons of non-synonymous and synonymous mutations in FOXP2 suggest that it occurred from 300,000 to 400,000 years ago. Too early to account for the relatively recent development of art which appeared approximately 50,000 years ago. Synonymous Mutations: no change in the amino acid residue encoded in the protein; neutral; molecular clock. Nonsynonymous Mutations: change the amino acid. Ratio of nonsynonymous to synonymous mutations gives indication of selection pressure. Number of synonymous mutations within a population gives a measure of the time elapsed: molecular clock. This slide is important This slide is important for Exam 11 for Exam FoxP2 transcription factor DNA binding domain Mutations at sites 303 and 325 distinguish humans from other primates. Zhang, Webb and Podlaha (2002) Accelerated Protein Evolution and Origins of Human-Specific Features: FOXP2 an exmple. Genetics 162: 1825-1835. FoxP2 transcription factor: mutations in modern humans Mutations at R553H (DNA binding domain) cause verbal dyspraxia, which affects articulation of language more than comprehension, and high speed movements of the vocal organs required for intelligible speech. FoxP2 transcription factor Arginine 553 is a part of helix 3 which is involved in DNA recognition. R553H mutants do not recognize the consensus DNA element in the promoter, and also are deficient in nuclear localization. Stroud et al. (2006) Structure of the Forkhead Domain of FOXP2 bound to DNA. Structure 14: 159-166. Evolution continues to change us. Lactose tolerance has arisen several times in the last 10,000 yrs. The best documented is that corresponding with the breeding of the milk cow in North Central Europe from 6,500-5,000 yrs ago associated with the Funnel Beaker culture. Peja-Pereira et al. (2003) Gene-culture coevolution between cattle milk protein genes and human lactase genes. Nature Gen. 35: 311-312. Man's Journey out of Africa http://www.bradshawfoundation.com/journey/ Origins of Modern Humans: Multiregional or Out of Africa? By Donald Johanson http://www.actionbioscience.org/evolution/johanson.html ...
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