Can genes help explain our evolution?- What type of changes (regulatory

or structural mutations?)

- How many genes are involved?

Approaches to Identify Genetic/Genomic Differences Between Chimps and Humans

1. Candidate gene approach

2. Microarray approach

3. Nucleotide substitution approach

4. Bioinformatic approach

Enard, W. et al. 2002. Molecular evolution of FOXP2, agene involved in speech and language. Nature 418, 869-872.

Candidate gene approach: FOXP2

- 2 non-conservative amino acid substitutions in humans-- flanking genomic DNA showed signs of a selective sweep

Signature of a Selective Sweep

Reduced polymorphismMore rare alleles

FavoredAllele

SelectionFixation

RecombinationMutation

• FOXP2 is expressed highly in zebra finches during the vocal learning period of development.Haesler et al. 2004. J. Neurosci 24:3164.

• FOXP2 knock-out mice have altered motorsensoryfunctions and ultrasonic vocalizations.Shu et al. 2005. PNAS 102:9643.

FOXP2 plays a role in the development of brain regions that are important for communication

Pollard, KS et al. An RNA gene expressed during corticaldevelopment evolved rapidly in humans. Nature Aug. 2006

• Scanned the 2/3 portion of the genome that is non-coding

• Many of the identified regions are associated with transcription factors and neurodevelopment genes.

• The most dramatically changed element (HAR1) is a novel RNA gene expressed during human cortical development.

Identified Human Accelerated Regions (HARs)

- Search chimpanzee genome sequence against rat and mouse genome sequences. (96% identity > 100 bp)

- 35,000 regions identified

- Searched these regions in all other available amniote genomes searching for regions with significant changes in human.

- 49 regions identified with a statistically significant rate increase in humans (96% in non-coding regions, 24% next to a neurodevelopmental gene)

Details of the Screening Process