Concerning the attached file, answer each of the four questions in paragraph form:
1. Describe in	your	own	words the	thesis of	the	author(s).	What do	they believe are the	important	features of this application of genetic biotechnology?
2. How	does	this	biotechnology	application	work?	What	features	of	DNA and	cells	are	being	used?
3. Describe	two	specific	examples	of	experimental	evidence	that	the authors	refer	to	are	examples	or	support	for	further	use	of	this technology?
4. What	is	one	example	of	a	specific	limitation	or	technical	‘hurdle’	that must	be	worked	around	or	overcome in	furthering	this	use	of technology.


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E VOLUTION

WHAT MAKES US

HUMAN?
Comparisons of the genomes of humans and chimpanzees are revealing those
rare stretches of DNA that are ours alone
By Katherine S. Pollard

S
KEY CONCEPTS
?

?

?

Chimpanzees are the
closest living relatives of
humans and share nearly
9 9 percent of our DNA.
Efforts to identify those
regions of the human
g enome that have
changed the most since
chimps and humans di verged from a common
ancestor have helped pin point the DNA sequences
that make us human.
The ndings have also
provided vital insights
into how chimps and
humans can differ so
profoundly, despite
having nearly identical
DNA blueprints.
—The

44

Editors

SCIENTIFIC AMERICAN

ix years ago I jumped at an opportunity
to join the international team that was
identifying the sequence of DNA bases,
or “letters,” in the genome of the common chimpanzee (Pan troglodytes). A s a biostatistician
with a long-standing interest in human origins,
I was eager to line up the human DNA sequence
next to that of our closest living relative and
t ake stock. A humbling truth emerged: our
DNA blueprints are nearly 99 percent identical
to theirs. That is, of the three billion letters that
make up the human genome, only 15 million of
them— less than 1 percent— have changed in the
six million years or so since the human and
chimp lineages diverged.
Evolutionary theory holds that the vast majority of these changes had little or no effect on
our biology. But somewhere among those roughly 15 million bases lay the differences that made
us human. I was determined to nd them. Since
then, I and others have made tantalizing progress in identifying a number of DNA sequences
that set us apart from chimps.

An Early Surprise
Despite accounting for just a small percentage
of the human genome, millions of bases are still
a vast territory to search. To facilitate the hunt,
I wrote a computer program that would scan the

human genome for the pieces of DNA that have
changed the most since humans and chimps
split from a common ancestor. Because most
random genetic mutations neither bene t nor
harm an organism, they accumulate at a steady
rate that re ects the amount of time that has
passed since two living species had a common
forebear (this rate of change is often spoken of
as the “ticking of the molecular clock”). Acceleration in that rate of change in some part of the
genome, in contrast, is a hallmark of positive
s election, in which mutations that help an
organism survive and reproduce are more likely
to be passed on to future generations. In other
words, those parts of the code that have undergone the most modi c ation since the chimphuman split are the sequences that most likely
shaped humankind.
In November 2004, after months of debugging and optimizing my program to run on a
massive computer cluster at the University of
California, Santa Cruz, I nally ended up with
a le that contained a ranked list of these rapidly evolving sequences. With my mentor David
Haussler leaning over my shoulder, I looked at
the top hit, a stretch of 118 bases that together
became known as human accelerated region 1
(HAR1). Using the U.C. Santa Cruz genome
browser, a visualization tool that annotates the

© 20 09 SCIENTIFIC AMERIC AN, INC.

May 2009

THE 1 P ERCEN T D IFFERENCE:

JAMES BALOG G etty Images

Humans are distinct from chimpanzees in a number of important respects, despite sharing
nearly 99 percent of their DNA.
New analyses are revealing
which parts of the genome set
our species apart.

human genome with information from public
databases, I zoomed in on HAR1. The browser
s howed the HAR1 sequences of a human,
chimp, mouse, rat and chicken— all of the vertebrate species whose genomes had been decoded by then. It also revealed that previous largescale screening experiments had detected HAR1
activity in two samples of human brain cells, although no scientist had named or studied the sequence yet. We yelled, “Awesome!” in unison
when we saw that HAR1 might be part of a gene
new to science that is active in the brain.
We had hit the jackpot. The human brain is
well known to differ considerably from the
chimpanzee brain in terms of size, organization
and complexity, among other traits. Yet the developmental and evolutionary mechanisms underlying the characteristics that set the human
brain apart are poorly understood. HAR1 had
the potential to illuminate this most mysterious
aspect of human biology.
We spent the next year nding out all we
could about the evolutionary history of HAR1
by comparing this region of the genome in variw w w. S c i A m . c o m

ous species, including 12 more vertebrates that
were sequenced during that time. It turns out
that until humans came along, HAR1 evolved
extremely slowly. In chickens and chimps —
whose lineages diverged some 300 million years
ago — only two of the 118 bases differ, compared with 18 differences between humans and
chimps, whose lineages diverged far more re cently. The fact that HAR1 was essentially fro zen in time through hundreds of millions of
years indicates that it does something very important; that it then underwent abrupt revision
in humans suggests that this function was signi cantly modi ed in our lineage.
A critical clue to the function of HAR1 in the
brain emerged in 2005, after my collaborator
Pierre Vanderhaeghen of the Free University of
Brussels obtained a vial of HAR1 copies from
our laboratory during a visit to Santa Cruz. He
used these DNA sequences to design a uorescent molecular tag that would light up when
H AR1 was activated in living cells — that is,
copied from DNA into RNA. When typical
genes are switched on in a cell, the cell rst
© 20 09 SCIENTIFIC AMERIC AN, INC.

SCIENTIFIC AMERICAN

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SCIENTIFIC AMERICAN

[E X PERIM ENT]

SC ANNING THE GENOME

To nd the parts of our genome that make us human, the author wrote a computer pro gram that searched for the DNA sequences that have changed the most since humans and
chimpanzees diverged from their last common ancestor. Topping the list was a 118-letter
snippet of code known as human
Human
accelerated region 1 (HAR1). This
Common ancestor of
region of the genome changed very
humans and chimps
little for most of vertebrate evoluChimp
6 million
tion, with chimp and chicken se years ago
quences differing by just two letters.
Human and chimp HAR1s, however, 300 million
years ago
differ by 18 letters, suggesting that
HAR1 acquired an important new
Common ancestor of
function in humans.
Chicken

humans and chickens
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