What makes us human?
Download
1 / 15

Katherine S. Pollard Gladstone Institutes, Institute for Human Genetics and Division of Biostatistics - UCSF http: - PowerPoint PPT Presentation


  • 179 Views
  • Uploaded on

What makes us human?. Katherine S. Pollard Gladstone Institutes, Institute for Human Genetics and Division of Biostatistics - UCSF http://docpollard.com. BioForum - California Academy of Sciences October 3, 2009. Chimpanzee: Pan troglodytes. Our closest living relative

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Katherine S. Pollard Gladstone Institutes, Institute for Human Genetics and Division of Biostatistics - UCSF http:' - mardi


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
Slide1 l.jpg

What makes us human?

Katherine S. Pollard

Gladstone Institutes, Institute for Human Genetics and Division of Biostatistics - UCSF

http://docpollard.com

BioForum - California Academy of Sciences

October 3, 2009


Chimpanzee pan troglodytes l.jpg
Chimpanzee: Pan troglodytes

Our closest living relative

(MRCA ~6 million years ago)


Comparative medicine l.jpg
Comparative Medicine

Leading Causes of Death

  • Naturally occurring variation in disease

  • susceptibility likely has some genetic basis.

  • What DNA changes are responsible?


Slide4 l.jpg

Human genome 2001

Mouse genome 2002

Chimp genome 2005



The chimp genome project l.jpg

How different are our genes?

~30% of proteins are identical

Average protein has 2 amino acid changes (1 per lineage)

15 genes where human disease variant is the only version in the chimp population  are we evolving away from ancestral version?

The Chimp Genome Project


Evolution of human digestion l.jpg

Our diet has changed a lot …

Cooking: tubers, other hard foods

Agriculture: grains, gluten

Animal husbandry: dairy, eggs, more meat

Some genes have adapted

Lactose tolerance (LCT gene)

High starch food sources (AMY gene)

 Vary between worldwide human populations

Evolution of Human Digestion


Non coding junk dna l.jpg
Non-coding ≠ “junk DNA”

  • ~5% of the human genome is functionally constrained and highly conserved in the mouse genome.

  • But only ~1% codes for proteins.

     Most constrained sequences are non-coding

Siepel et al. 2005


Slide9 l.jpg

Human

Chimp

Gorilla

Old World Monkeys

New World Monkeys

Mouse

Chicken

Fish

Comparative Genomics 2009

6mya

8mya

44 vertebrates

20 genome projects

24 2x mammals

25mya

35mya

75mya

~300mya

~400mya


Slide10 l.jpg

Substitution Rates

Much of the DNA in eukaryotic genomes is evolving at a background (neutral) rate:

Negative selection on functional elements decreases the number of substitutions:

  • Other forces increase substitutions...

  • Positive selection

  • Mutation rate increase


Human accelerated regions l.jpg

HAR1: novel RNA gene

Likelihood Ratio Test

Human

Mouse

Altered regulation of developmental genes

Guillemot Lab

HAR2: limb enhancer

Rubin Lab

Human Accelerated Regions

Human-Chimp Differences

202 Human Accelerated Regions (HARs)

Highly Conserved Elements

Pollard et al. (2006) Nature, Pollard et al. (2006) PLoS Genetics


Location of hars l.jpg

11 predicted RNA genes

38 change a known TF binding site

ITPR1, SPRY4, hypothetical protein

NGN2 (3’ UTR)

Location of HARs

  • Mostly non-coding elements

    • 66% intergenic

    • 32% intronic

    • 1.5% protein coding

    • 0.5% UTR

  • Nearby genes involved in transcriptional regulation, development, and disease.

  • HAR170

  • Intron of the “speech

  • gene” FOXP2

  • RNA structure

  • Many human changes


What have we learned l.jpg
What have we learned?

  • Being human is not all about the brain.

  • Proteins are nearly identical to chimp’s.

  • We need to decipher the effects of non-coding changes, e.g. gene regulation.

  • 99% vs. 99.9% identity  human genomes

Pollard (2009) Scientific American


Collaborators l.jpg
Collaborators

University of California, Santa Cruz Gladstone Institutes, UCSF

David Haussler Dennis Kostka

Sofie Salama Genevieve Erwin

Tim Dreszer Alisha Holloway

Adam Siepel (Cornell) Joshua Ladau

Jakob Pedersen (Copenhagen)Samantha Riesenfeld Thomas Sharpton

University of Brussels (ULB), Belgium Alex Zambon (UCSD)

Pierre Vanderhaeghen

Nelle Lambert Uppsala University

Marie-Alexandra Lambot Matthew Webster

Sandra Coppens Jonus Berglund

National Institute for Medical Research Indiana University (MRC), England Matthew Hahn

Francois Guillemot

Laura Galinanes-Garcia


ad