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Description : Check out this medical titled "The Human Genome and Human Evolution” by Chris Tyler-Smith.

This medical is about the human genome, the complete set of genetic instructions that make up a human being. It contains all the information necessary for the development and function of every cell in the body. The study of the human genome has had a significant impact on our understanding of human evolution.

Human evolution refers to the gradual process by which humans have evolved from earlier primates over millions of years. Scientists have used the study of the human genome to trace our evolutionary history and identify the genetic changes that have occurred over time.

One of the most significant findings of the study of the human genome is that all modern humans share a common ancestor who lived in Africa around 200,000 years ago. This ancestor is known as the "mitochondrial Eve," and her DNA has been passed down to all living humans through our mothers.

Through the study of the human genome, scientists have also identified genetic differences between humans and other primates, such as chimpanzees and gorillas. These differences have helped researchers understand the genetic changes that have occurred over millions of years of evolution.

In addition, the study of the human genome has shed light on the genetic variations that exist among different human populations. These variations have helped researchers understand how humans have adapted to different environments and how they have evolved over time.

Overall, the study of the human genome has provided valuable insights into human evolution and our genetic history. It has helped us better understand our place in the natural world and the biological processes that have shaped us as a species.

Tags : Human Genome, Human Evolution, genetic instructions, Medical Genetics, Medical Genetics

Published on : Jun 01, 2023 | Views : 1214 | Downloads : 0

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Slide 1-

The Human Genome and Human Evolution Chris Tyler-Smith The Wellcome Trust Sanger Institute
Slide 2-

Outline Information from fossils and archaeology Neutral (or assumed-to-be-neutral) genetic markers Classical markers Y chromosome Demographic changes Genes under selection Balancing selection Positive selection
Slide 3-

Who are our closest living relatives? Chen FC & Li WH (2001) Am. J. Hum. Genet. 68 444-456
Slide 4-

Phenotypic differences between humans and other apes Carroll (2003) Nature 422, 849-857
Slide 5-

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

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) Nature 418, 145-151
Slide 7-

Hominid fossil summary Found only in Africa Found both in Africa and outside, or only outside Africa
Slide 8-

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
Slide 9-

Additional migrations out of Africa First known Europeans date to ~800 KYA Ascribed to H. heidelbergensis Atapueca 5, Spain, ~300 KYA
Slide 10-

Origins of modern humans (1) Anatomically modern humans in Africa ~130 KYA In Israel by ~90 KYA Not enormously successful Omo I, Ethiopia, ~130 KYA
Slide 11-

Origins of modern humans (2) Modern human behaviour starts 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
Slide 12-

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
Slide 13-

Routes of migration?archaeological evidence Middle Stone Age Upper Paleolithic ~130 KYA
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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 Did they leave descendants? 14
Slide 15-

Mixing or replacement?
Slide 16-

Human genetic diversity is low
Slide 17-

Human genetic diversity is evenly distributed Most variation between populations Most variation within populations Templeton (1999) Am. J. Anthropol. 100, 632-650
Slide 18-

Phylogenetic trees commonly indicate a recent origin in Africa Y chromosome
Slide 19-

Modern human mtDNA is distinct from Neanderthal mtDNA Krings et al. (1997) Cell 90, 19-30
Slide 20-

Classical marker studies Based on 120 protein-coding genes in 1,915 populations Cavalli-Sforza & Feldman (2003) Nature Genet. 33, 266-275
Slide 21-

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
Slide 22-

Y haplogroup distribution Jobling & Tyler-Smith (2003) Nature Rev. Genet. 4, 598-612
Slide 23-

An African origin
Slide 24-

SE Y haplogroups
Slide 25-

NW Y haplogroups
Slide 26-

Did both migrations leave descendants? General SE/NW genetic distinction fits two-migration model Basic genetic pattern established by initial colonisation All humans outside Africa share same subset of African diversity (e.g. Y: M168, mtDNA: L3) Large-scale replacement, or migrations were not independent How much subsequent change?
Slide 27-

Fluctuations in climate Ice ages Antarctic ice core data Greenland ice core data
Slide 28-

Possible reasons for genetic change Adaptation to new environments Food production – new diets Population increase – new diseases
Slide 29-

Debate about the Paleolithic-Neolithic transition Major changes in food production, lifestyle, technology, population density Were these mainly due to movement of people or movement of ideas? Strong focus on Europe
Slide 30-

Estimates of the Neolithic Y contribution in Europe ~22% (=Eu4, 9, 10, 11); Semino et al. (2000) Science 290, 1155-1159 >70% (assuming Basques = Paleolithic and Turks/Lebanese/ Syrians = Neolithic populations); Chikhi et al. (2002) Proc. Natl. Acad. Sci. USA 99, 11008-11013
Slide 31-

More recent reshaping of diversity ‘Star cluster’ Y haplotype originated in/near Mongolia ~1,000 (700-1,300) years ago Now carried by ~8% of men in Central/East Asia, ~0.5% of men worldwide Suggested association with Genghis Khan Zerjal et al. (2003) Am. J. Hum. Genet. 72, 717-721
Slide 32-

Is the Y a neutral marker? Recurrent partial deletions of a region required for spermatogenesis Possible negative selection on multiple (14/43) lineages Repping et al. (2003) Nature Genet. 35, 247-251
Slide 33-

Demographic changes Population has expanded in range and numbers Genetic impact, e.g. predominantly negative values of Tajima’s D Most data not consistent with simple models e.g. constant size followed by exponential growth
Slide 34-

Selection in the human genome time Neutral Negative (Purifying, Background) Balancing Positive (Directional) Bamshad & Wooding (2003) Nature Rev. Genet. 4, 99-111
Slide 35-

The Prion protein gene and human disease Prion protein gene PRNP linked to ‘protein-only’ diseases e.g. CJD, kuru A common polymorphism, M129V, influences the course of these diseases: the MV heterozygous genotype is protective Kuru acquired from ritual cannibalism was reported (1950s) in the Fore people of Papua New Guinea, where it caused up to 1% annual mortality Departure from Hardy-Weinberg equilibrium for the M129V polymorphism is seen in Fore women over 50 (23/30 heterozygotes, P = 0.01)
Slide 36-

Non-neutral evolution at PRNP McDonald-Kreitman test N S Diversity 5 1 Divergence (Gibbon) 2 13 ‘coding’ ‘non-coding’ P-value = 0.0055 Resequence coding region in ? humans and apes Mead et al. (2003) Science 300, 640-643
Slide 37-

Balancing selection at PRNP Observed Expected 24 SNPs in 4.7 kb region, 95 haplotypes Excess of intermediate-frequency SNPs: e.g. Tajima’s D = +2.98 (Fore), +3.80 (CEPH families) Deep division between the M and V lineages, estimated at 500,000 years (using 5 MY chimp-human split)
Slide 38-

Neutral Selection Derived allele of SNP Effect of positive selection
Slide 39-

What changes do we expect? New genes Changes in amino-acid sequence Changes in gene expression (e.g. level, timing or location) Changes in copy number
Slide 40-

How do we find such changes? Chance φhHaA type I hair keratin gene inactivation in humans Identify phenotypic changes, investigate genetic basis Identify genetic changes, investigate functional consequences
Slide 41-

Inheritance of a language/speech defect in the KE family Lai et al. (2000) Am. J. Hum. Genet. 67, 357-367 Autosomal dominant inheritance pattern
Slide 42-

Mutation and evolution of the FOXP2 gene Chr 7 7q31 FOXP2 gene Nucleotide substitutions silent replacement Enard et al. (2002) Nature 418, 869-872
Slide 43-

Positive selection at the FOXP2 gene Resequence ~14 kb of DNA adjacent to the amino-acid changes in 20 diverse humans, two chimpanzees and one orang-utan No reduction in diversity Excess of low-frequency alleles (Tajima’s D = -2.20) Excess of high-frequency derived alleles (Fay & Wu’s H =-12.24) Simulations suggest a selective sweep at 0 (0 – 200,000) years Orang Gorilla Chimp Human silent (synonymous) dS replacement (non-synonymous) dN Human-specific increase in dN/dS ratio (P<0.001) Constant rate of amino-acid replacements? Positive selection in humans? Enard et al. (2002) Nature 418, 869-872
Slide 44-

A gene affecting brain size Microcephaly (MCPH) Small (~430 cc v ~1,400 cc) but otherwise ~normal brain, only mild mental retardation MCPH5 shows Mendelian autosomal recessive inheritance Due to loss of activity of the ASMP gene ASPM-/ASPM- control Bond et al. (2002) Nature Genet. 32, 316-320
Slide 45-

Evolution of the ASPM gene (1) Summary dN/dS values Orang Gorilla Chimp Human Human-specific increase in dN/dS ratio (P<0.03) 1.44 0.56 0.56 0.53 0.52 0.62 Sliding-window dN/dS analysis Evans et al. (2004) Hum. Mol. Genet. 13, 489-494
Slide 46-

Evolution of the ASPM gene (2) N S Diversity 6 10 Divergence 19 7 Evans et al. (2004) Hum. Mol. Genet. 13, 489-494 Sequence ASPM coding region from 40 diverse individuals and one chimpanzee P-value = 0.025 McDonald-Kreitman test
Slide 47-

What changes? FOXP2 is a member of a large family of transcription factors and could therefore influence the expression of a wide variety of genes The Drosophila homolog of ASPM codes for a microtubule-binding protein that influences spindle orientation and the number of neurons do Carmo Avides and Glover (1999) Science 283, 1773-1735 DNA Microtubules asp Subtle changes to the function of well-conserved genes
Slide 48-

Genome-wide search for protein sequence evolution 7645 human-chimp-mouse gene trios compared Most significant categories showing positive selection include: Olfaction: sense of smell Amino-acid metabolism: diet Development: e.g. skeletal Hearing: for speech perception Clark et al. (2003) Science 302, 1960-1963
Slide 49-

Gene expression differences in human and chimpanzee cerebral cortex Increased expression Decreased expression Caceres et al. (2003) Proc. Natl. Acad. Sci. USA 100, 13030-13035 Affymetrix oligonuclotide array (~10,000) genes 91 show human-specific changes, ~90% increases
Slide 50-

Copy number differences between human and chimpanzee genomic DNA Human male reference genomic DNA hybridised with female chimpanzee genomic DNA Locke et al. (2003) Genome Res. 13, 347-357
Slide 51-

Selection at the CCR5 locus CCR532/CCR532 homozygotes are resistant to HIV and AIDS The high frequency and wide distribution of the 32 allele suggest past selection by an unknown agent
Slide 52-

Lactase persistence All infants have high lactase enzyme activity to digest the sugar lactose in milk In most humans, activity declines after weaning, but in some it persists: LCT*P
Slide 53-

Molecular basis of lactase persistence Lactase level is controlled by a cis-acting element Linkage and LD studies show association of lactase persistence with the T allele of a T/C polymorphism 14 kb upstream of the lactase gene Enattah et al. (2002) Nature Genet. 30, 233-237
Slide 54-

The lactase-persistence haplotype The persistence-associated T allele occurs on a haplotype (‘A’) showing LD over > 1 Mb Association of lactase persistence and the A haplotype is less clear outside Europe
Slide 55-

Selection at the G6PD gene by malaria Reduced G6PD enzyme activity (e.g. A allele) confers some resistance to falciparum malaria Extended haplotype homozygosity at the A allele Sabeti et al. (2002) Nature 419, 832-837
Slide 56-

Final words Is there a genetic continuum between us and our ancestors and the great apes? If there is, then we can say that these [i.e. microevolutionary] processes are genetically sufficient to fully account for human uniqueness — and that would be my candidate for the top scientific problem solved in the first decade of the new millennium. Nature 427, 208-209 (2004)
Slide 57-

Further reading Jobling MA, Hurles ME, Tyler-Smith C (2004) Human Evolutionary Genetics. Garland Science (General textbook) Carroll SB (2003) Genetics and the making of Homo sapiens. Nature, 422, 849-857 (Broad-ranging review) Paabo S (2003) The mosaic that is our genome. Nature 421, 409-412 (Review) Cavalli-Sforza LL, Feldman MW (2003) The application of molecular genetic approaches to the study of human evolution. Nature Genet. 33, 266-275 (Review) Stringer C (2002) Modern human origins. Phil. Trans. R. Soc. Lond. B 357, 563-579 (Fossils and archaeology) Forster P (2004) Ice Ages and the mitochondrial DNA chronology of human dispersals: a review. Phil. Trans. R. Soc. Lond. B 359, 255-264 (mtDNA) Jobling MA, Tyler-Smith C (2003) The human Y chromosome: an evolutionary marker comes of age. Nature Rev. Genet. 4, 589-612 (Y chromosome) Bamshad M, Wooding SP (2003) Signatures of natural selection in the human genome. Nature Rev. Genet. 4, 99-111