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Human Evolution Genes and Genomes Lecture 2: Becoming Human ,[object Object]
Humans are not chimps ,[object Object],[object Object],[object Object],[object Object],[object Object]
What can genes and genomes hope to tell us? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Genomes sequenced Human genome: complete Chimp genome: draft Orang genome: in progress Macaque genome: draft Neanderthal genome sample sequenced
Single male chimp: Clint
What makes us human? ,[object Object],[object Object],[object Object],[object Object],[object Object]
What makes us human? ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Human & Chimp Genomes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Changes in chromosome structure Human Chromosome 2 Chimpanzee Chromosomes 2a & 2b Chromosome fusion: Segmental  duplications: Humans: 13.7% Chimps: ~5% of the genome is segmentally duplicated Inversions: Multiple inversions between humans and chimpanzees Translocations: In humans  an X=>Y translocation resulted in formation of the second pseudo- autosomal region
Modes and models of evolution
 
 
 
Evolution of gene expression Search for human-specific changes in gene expression Human  bonobo  chimp  gorilla A set of genes with human-specific changes in expression Pollard et al Nature 2006
Human & Chimp Genomes ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Differences in biology ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
FOXP2 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Evolution of human FOXP2 gene Mutations in the human  FOXP2  gene are associated with an autosomal dominant form of dysarthria (difficulty in articulating speech). The human  FOXP2  gene shows changes in amino acid coding and a pattern of nucleotide polymorphisms that suggest this gene has undergone positive selection during recent human evolution (Enard  et al  2002  Nature )
FOXP2 in mice ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
HAR1 ,[object Object],[object Object],[object Object],[object Object],[object Object]
Two distinct experimentally supported secondary structure models for HAR1 RNAs Beniaminov A et al. RNA 2008;14:1270-1275
AMY1 ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
“ Brain-building” genes ,[object Object],[object Object],[object Object],[object Object]
[object Object],variants more common in Eurasians than in Africans…
Subsequent studies find no links found between microcephalin variant and IQ or brain size AND these genes are also expressed outside the brain Merely tracking out of Africa migration?
 
MYH16
MYH16
KRTHAP1
HAR2/HACNS1 “ The dexterity of the human hand is due to morphological differences compared with other primates that include rotation of the thumb toward the palm and an increase in the length of the thumb relative to the other digits. Human-specific changes in hindlimb morphology, such as the characteristic inflexibility and shortened digits of the human foot, facilitated habitual bipedalism. The gain of function in HACNS1 may have influenced the evolution of these or other human limb features by altering the expression of nearby genes during limb development.”
 
 
 
 
Summary ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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Human Evolution Genes and Genomes Lecture: What Makes Us Human

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  • 4. Genomes sequenced Human genome: complete Chimp genome: draft Orang genome: in progress Macaque genome: draft Neanderthal genome sample sequenced
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  • 9. Changes in chromosome structure Human Chromosome 2 Chimpanzee Chromosomes 2a & 2b Chromosome fusion: Segmental duplications: Humans: 13.7% Chimps: ~5% of the genome is segmentally duplicated Inversions: Multiple inversions between humans and chimpanzees Translocations: In humans an X=>Y translocation resulted in formation of the second pseudo- autosomal region
  • 10. Modes and models of evolution
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  • 14. Evolution of gene expression Search for human-specific changes in gene expression Human bonobo chimp gorilla A set of genes with human-specific changes in expression Pollard et al Nature 2006
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  • 20. Evolution of human FOXP2 gene Mutations in the human FOXP2 gene are associated with an autosomal dominant form of dysarthria (difficulty in articulating speech). The human FOXP2 gene shows changes in amino acid coding and a pattern of nucleotide polymorphisms that suggest this gene has undergone positive selection during recent human evolution (Enard et al 2002 Nature )
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  • 23. Two distinct experimentally supported secondary structure models for HAR1 RNAs Beniaminov A et al. RNA 2008;14:1270-1275
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  • 27. Subsequent studies find no links found between microcephalin variant and IQ or brain size AND these genes are also expressed outside the brain Merely tracking out of Africa migration?
  • 28.  
  • 29. MYH16
  • 30. MYH16
  • 32. HAR2/HACNS1 “ The dexterity of the human hand is due to morphological differences compared with other primates that include rotation of the thumb toward the palm and an increase in the length of the thumb relative to the other digits. Human-specific changes in hindlimb morphology, such as the characteristic inflexibility and shortened digits of the human foot, facilitated habitual bipedalism. The gain of function in HACNS1 may have influenced the evolution of these or other human limb features by altering the expression of nearby genes during limb development.”
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Notas del editor

  1. Two distinct experimentally supported secondary structure models for HAR1 RNAs. (A) The cloverleaf-like model of the human HAR1 RNA. (B) The chimpanzee HAR1 RNA adopts a hairpin structure. The length and thickness of the symbols represent the intensity of the cleavages. Bases reactive to DMS or CMCT under native conditions are circled; weak reactivities are depicted by dotted circles. Bases modified by CMCT under semidenaturing conditions only are displayed with a green background. H, helix; IL, internal loop; L, loop.