Lecture 2: Becoming human What have comparisons between human and ape genomes taught us about what it means to be human?

4. Genomes sequenced Human genome: complete Chimp genome: draft Orang genome: in progress Macaque genome: draft Neanderthal genome sample sequenced

5. Single male chimp: Clint

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

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

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 )

23. Two distinct experimentally supported secondary structure models for HAR1 RNAs Beniaminov A et al. RNA 2008;14:1270-1275

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?

29. MYH16

30. MYH16

31. KRTHAP1

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.”