DNA: THE ULTIMATE FORENSIC RECORD OF

EVOLUTION

(Beyond Stones and Bones)

How molecular genetics is expanding our understanding

of the tree of life

Page from Darwin's notebooks around July 1837 showing his first known sketch of an evolutionary tree.

The Year 2009

Marks the bicentennial of Charles Darwin’s birth. (Born Feb. 12, 1809)

and the

150th anniversary of the publication of the Origin of Species (1st edition published 1859)

Theodosious Dobzhansky

In the Descent of Man, Darwin:

Declared the chimpanzee and gorilla our closest living relatives based on anatomical similarities, and he made this prediction: “It is, therefore probable….our early progenitors lived on the African continent…”

Nature of Science

“Scientific knowledge is simultaneously reliable and tentative. Having confidence in scientific knowledge is reasonable while realizing that such knowledge may be abandoned or modified in light of new evidence….. .”

NSTA Position Statement “The Nature of Science”July 2000

Titcomb Basin, Wind River Mtns, Wyoming -

PRIMATES

Prosimians Tarsiers Anthropoids

New-world Monkeys

Old-world Monkeys

Hominoids

Pongids (apes)

Hominids (humans)

Primate Classification

Note: Primate classification is undergoing rapid change. This is a simplified version of one of several taxonomies.

PRIMATES - Hominoids

Chimpanzee

(Pongid)

Gorilla

(Pongid)

Orangutan

(Pongid)

Human

(Hominid)

The known fossil record of hominids also showing ourselves and the chimpanzee

Skull cast used in DE Grade 10 NSE unit

All the DNA contained in an organism or a cell, which includes both the chromosomes within the nucleus and the DNA in mitochondria.

All of the biological information (DNA) needed to build and maintain a living example of that organism.

National Center for Biotechnology Information

The Human Genome Project• Draft completed April 2003, refined in 2006

• International effort

• Cost $3 billion

• ~ 3 billion base pairs

• Haploid set of DNA

• Early draft indicated ~ 30000 – 35000 protein coding genes

• Current estimate puts number of protein coding genes at ~ 20,500

A chimpanzee named Clint was the source of the DNA for the genome study. Clint lived at the Yerkes Primate Research Center near Atlanta until he died in 2004 at the age of 24.

Chimp Genome Sequenced in 2005

3 billion base pairs in sequence

96% of chimp & human DNA sequences are identical

• 1.2% difference when considering single base pair substitutions

• additional 2.7% difference considering duplications and rearrangements

http://www.newscientist.com/article/dn16224-neanderthal-genome-already-giving-up-its-secrets.html

NEANDERTHAL GENOME

December 2008

Half of nuclear DNA sequenced from bone sample. Some Preliminary Results:

Lacked genes for lactose tolerance, increased fertility, and microcephalin which is linked to bulging brains in humans.

Did they interbreed with modern humans? Probably not. Europeans and Africans appear to have equal numbers of genetic differences with Neanderthals, suggesting that the first anatomically modern humans to arrive in Europe replaced Neanderthals.

August 2008

A complete mitochondrial (mt) genome sequence was reconstructed from bone of a 38,000 year-old Neandertal individual. Analysis establishes that the Neandertal mtDNA falls outside the variation of extant human mtDNAs, and allows an estimate of the divergence date between the two mtDNA lineages of 660,000 + or - 140,000 years.

http://www.cell.com/abstract/S0092-8674(08)00773-3

What is surprising, puzzling or paradoxical about?

The number of protein coding genes in:E. coli (bacterium) 4,377 Saccharomycetes (yeast) ~ 5,000Neurospora (fungus) ~10,000 Drosophilia (fruit fly) ~13,600C. elegans (nematode) ~20,000 Arabidopsis (plant) ~ 25,000Zea mays (corn) ~50,000 Humans & most mammals ~20,500

Protein coding genes make up about 2% of the human genome.

All organisms (archaea, bacteria, eukaryotes) share ~ 500 genes.

There are about 90,000 different proteins in the human body.

Humans have 46 chromosomes, chimps have 48.

The other 98% of the genome

Transposable Elements and Evolution

All 7 Alu elements in Human and Chimp hemoglobin are in exactly same place.

The DNA sequences in the 7 Alu elements range in similarity from 94.7% to 98.9%

The other 98% of the genome

Short Tandem RepeatsSTR’s (short tandem repeats) and VNTR’s (variable tandem repeats) are used in forensics and genealogy

The FBI has chosen 13 specific STR loci to serve as the standard for CODIS. The likelihood that any two individuals (except identical twins) will have the same 13-loci DNA profile can be as high as 1 in 1 billion or greater.

STR repeats for D81179 Locus

In this example the STR TCTA is repeated 12 times

The other 98% of the genome

Short Tandem Repeats

February 8, 2006

Love You, K2a2a, Whoever You Are

Amy Harmon New York Times January 22, 2006

Amy Harmon’s mtDNA has the genetic marker of one of the four founding mothers of a large part of today’s Ashkenazi Jewish population.

Harmon discusses some of the positive outcomes as well as troubling issues surrounding genetic genealogy.

MtDNA and Y- Chromosome Studies

•mtDNA comparisons along maternal lines of descent trace all modern humans to a woman (Eve) who lived in Africa less than 200,000 years ago.

• Y-chromosome studies along paternal lines indicate that all modern humans alive today are descended from a man (Adam) who lived in Africa about 60,000 years ago.

Maternally inherited

• 16,569 base pairs encode 37 genes involved in energy production and storage.

• Polymorphisms in the D-loop or hypervariable region are useful in human diversity studies. This is a non-coding region.

MtDNA Genome

Mitochondrial Eve – The Initial StudyRebecca Cann, Mark Stoneking, and Allan Wilson, Nature, 1987.

• Sequenced mtDNA from the placentas of 147 women from many populations from the around earth.

• In their analysis, they assumed that if two mtDNA sequences shared a polymorphism, then they shared a common ancestor.

• By building up a network of the 147 sequences, they were able to infer ancestral relationships between the women.

THEIR CONCLUSION:

“All these mitochondrial DNA’s stem from one woman who is postulated to have lived about 200,000 years ago, probably in Africa”

UNIVERSAL MATERNAL ANCESTOR (Eve)

Determining the age of lineages using ‘molecular clocks’

Assumptions:

• Nucleotide changes occur over time at a regular clock-like rate.

Groups separated by 20 nucleotide changes have common ancestors twice as old as

those separated by 10 nucleotide changes.

• The rate of nucleotide change can be determined

To calibrate a molecular clock, researchers use the time of a lineage split for which there is a high degree of confidence about when it

occurred.

Example of Calculation

For mtDNA, the calibration was set at the human-chimp split 6 million years ago. Chimps and humans differ by about 12% in their mtDNA. Thus rate of change of hominid mtDNA is about 2% per million years.

The average total divergence of contemporary human sequences is about 0.4%. Thus the

divergence time is about 200,000 years.

Determining age using ‘molecular clocks’

THE HUMAN Y CHROMOSOME: AN EVOLUTIONARY

MARKER COMES OF AGE

Mark A. Jobling & Chris Tyler-Smith Nature Reviews Genetics 4, 598-612 01

Aug 2003

“The availability of the near complete chromosome sequence now provides new avenues for investigating human evolution.”

XY

mt DNA markers

Y markers

National Geographic

Genographic Project

Y Haplogroups

of the World

The International HapMap Project is a multi-country effort to identify and catalog genetic similarities and differences in human beings. Using the information in the HapMap, researchers will be able to find genes that affect health, disease, and individual responses to medications and environmental factors.

New York Times December 10, 2006

DNA Gatherers Hit a Snag: The Tribes Don't Trust ThemBy AMY HARMON

The Genographic Project has come to a standstill in North America.

Indigenous leaders fear that genetic ancestry information could jeopardize land rights and other benefits that are based on the notion that their people have lived in a place since the beginning of time.

CBS News October 10, 2006

Mad At ScienceSome Activists Say The Genographic Project Is Undermining Indigenous Cultures

The Indigenous Peoples Council on Biocolonialism says taking samples from indigenous groups undermines their belief systems. Here, the Genographic Project's leader, Dr. Spencer Wells, performs a cheek swab from a participant in Chad. 

Opposition to the Genographic Project

The other 98% of the genome

PSEUDOGENES (FOSSIL GENES)

Unitary

Duplication

Retro or Processed

Mutated non-functional genes

~19,000 (estimate in 2003)

Released from constraints of natural selection.

Accumulated mutations serve as fossil bed for studying evolutionary past.

Human GULO Unitary Pseudogene and Vitamin C

Mice and many mammals have a functional GULO gene that is involved in producing vitamin C.

The GULO gene in primates is a non-functional pseudogene. How might this have happened?

Use it or lose it.

Fossil genes are exactly what we would predict to evolve as a consequence of continued mutation in the absence of natural selection.

Fossil genes mark changes in lifestyle and when we can spot and track these genes it is possible to reconstruct ancestry.

With some exceptions humans and chimps have same pseudogenes in the same place, and on average are 98% identical.

The other 98% of the genome

Pseudogenes and Vitamin C

Gene 1

Enzyme 1

Gene 2

Enzyme 2

Gene 3

Enzyme 3

DB C Vitamin CA

GULOgene

Gulo Enz

Vitamin C

Not so in primates…

Portion of Working GULO Gene in Rat:

Matching GULO Pseudogenes in 4 PrimatesNote Deletion

In most mammals

The other 98% of the genome

HEMOGLOBIN DUPLICATION PSEUDOGEGES

Humans have 13 copies of genes that encode hemoglobin. Only 4 function in adults. These genes are located in two clusters, A & B. About 30% of psi-beta DNA sequence is mutated.

The other 98% of the genome

Other Pseudogenes

Cytrochrome c genes (49 in humans)

Color vision (opsin) genes (correlated to olfaction)

Olfactory genes (mice have 1,400)

18% fossilized in mice, lemurs, and New World monkeys that lack color vision.

29% fossilized in Old world Monkeys

33% fossilized in apes, chimps, and orangutans

50% fossilized in humans

Use it or lose it.

The Alternative Genome

The old axiom “one gene, one protein” no longer holds true.

The more complex an organism, the more likely it became that way by extracting multiple proteins from individual genes.

The genes of mice and humans are 88% alike. Many of the ways we differ from rodents arise from how we edit our genetic information.

Epigenesis

Epigenetics refers to changes in gene expression due to mechanisms other than changes in DNA sequence