2008 July/August. Tracing
Evolution in Genes. By Kathleen M. Wong, ScienceMatters@Berkeley.
Excerpt: How do humans differ from chimpanzees?
...we're taller, less hairy, and-a point no
one fails to mention-far brainier than our
closest primate relatives.
All of these differences and more have emerged
over the past five million years, when the
common ancestor of both species reached an
evolutionary fork in the road. How early hominids
came to walk the savannah, while early chimpanzees
returned to the forests, has fascinated professional
scientists and armchair anthropologists alike.
The best way to answer those questions, according
to Rasmus Nielsen, is to study our respective
genomes. "Evolutionary biology is an
historical science," says Nielsen, a
Berkeley professor of integrative biology. "But
in the absence of a time machine, we can't
really go back and show exactly why certain
evolutionary events occurred. All we have
to work with is what we observe today. So
we look at the DNA to see the evidence for
past Darwinian selection."
Nielsen uses the power of statistics and computing
to compare the DNA of different species or
populations. By identifying which sets of
genes have changed, or mutated, he can describe
how ancestral populations diverged step by
tiny genetic step. His work not only recasts
the story of human evolution but promises
to uncover the genetic roots of many diseases...
2008 May. Distant
Relatives, Common Genes. By
Kathleen M. Wong, ScienceMatters@Berkeley.
Excerpt: Glance
through any family's photo album, and you're
likely to home in on a few outstanding ancestral
traits. The shape of a nose or the arch of
an eyebrow can be passed down for generation
after generation.
Biologists have long studied commonalities
such as these to infer ancestral relationships
between animals. But the more distant the
relationship, such as between humans and sponges,
the trickier it is to establish connections
through simple comparisons of anatomy.
Dan Rokhsar, a Berkeley professor of both
physics and molecular and cellular biology,
and a faculty scientist at the Department
of Energy's Joint Genome Institute, is sidestepping
this problem via a different aspect of inheritance:
genes. Genes shared by distantly related animals
are likely to have originated in their last
common ancestor. So by sequencing and comparing
the genomes of creatures ranging from sea
anemones to sea squirts, limpets to pufferfish,
Rokhsar and his research team hope to reconstruct
characteristics of the great-great grandparents
to all animals.
"We're interested in that transition
from being a unicellular organism to being
multicellular-when it happened and how it
happened," Rokhsar says…
Recently, the skyrocketing price of petroleum
and the threat of global climate change have
turned Rokhsar's attention toward greener
subjects: plants…
"The cellulose and lignin in plant walls
is where all of the carbon goes from photosynthesis.
That's the carbon we want to convert to fuel.
How do they do it? One way to find an answer
is to look at genomes," Rokhsar says.
He is now working to sequence the genome of
switchgrass, a native plant and strong candidate
to produce biofuel…
"We need to collapse the 5,000 years
it took to breed maize into an edible plant
into 10 years for switchgrass, because we
don't have a lot of time to develop renewable
fuels," Rokhsar says. "And we'll
need to do this sustainably and as a solution
for the long term."
2008 April 22. Expressing
Our Individuality, the Way E. Coli Do. By CARL ZIMMER, The
NY Times. Excerpt:
We humans differ from one another in too
many ways to count...Scientists have only
a rough understanding of how this diversity
arises… We
put a far bigger premium on nature than
nurture when it comes to our individuality.
That’s one reason
why reproductive cloning inspires so much
horror. If genes equal identity, then a
person carrying someone else’s DNA
has no distinct self. But there’s
a deep flaw in this way of thinking, one
that blinds us to how biology — human
or otherwise — really works. A good
counterexample is E. coli, a species of bacteria
that lives harmlessly in every person’s
gut by the billions. A typical E. coli contains
about 4,000 genes (we have about 20,000).
Feeding on sugar, the microbe grows till it
is ready to split in two. It makes two copies
of its genome, almost always managing to produce
perfect copies of the original. The single
microbe splits in two, and each new E. coli
receives one of the identical genomes. These
two bacteria are, in other words, clones...E.
coli expresses its individuality in many other
ways, as well…These quirks of E. coli’s
personality can mean the difference between
life and death for the bacteria. In times
of stress, some members of a colony respond
by building thousands of toxin molecules and
then burst open, killing off the unrelated
E. coli around them. Their fellow clones survive,
though, and thrive without the competition.
The key to understanding E. coli’s fingerprints
is to recognize that the bacteria are not
simple machines. Unlike wires and transistors,
E. coli’s molecules are floppy, twitchy
and unpredictable. In an electronic device,
like a computer or a radio, electrons stream
in a steady flow through the machine’s
circuits, but the molecules in E. coli jostle
and wander. When E. coli begins using a gene
to make a protein, it does not produce a smoothly
increasing supply. It spurts out the proteins
in fits and starts. One clone may produce
half a dozen copies of a protein in an hour,
while a clone right next to it produces none.
Other studies suggest that the unpredictable
noisiness in E. coli’s cellular machinery
is also responsible for persistence, hairy
coats, selfless suicide and vulnerability
to viruses. The big question for many scientists
is why E. coli has evolved so that noise can
produce such drastic changes in its biology…
Identical genes can also behave differently
in our cells because some of our DNA is capped
by carbon and hydrogen atoms called methyl
groups. Methyl groups can control whether
genes make proteins or remain silent. In humans
(as well as in other organisms like E. coli),
methyl groups sometimes fall off of DNA or
become attached to new spots. Pure chance
may be responsible for changing some methyl
groups; nutrients and toxins may change others.
…At the very least, E. coli’s
individuality should be a warning to those
who would put human nature down to any sort
of simple genetic determinism. Living things
are more than just programs run by genetic
software. Even in minuscule microbes, the
same genes and the same genetic network can
lead to different fates.
2008 March 4. Gene
Map Becomes a Luxury Item.
by Amy Harmon. The New York Times. Excerpt:
Dan Stoicescu, 56, a biotechnology entrepreneur
who retired two years ago after selling
his company, became the second person in
the world to buy the full sequence of his
own genetic code paying $350,000 price tag.
Scientists have so far unraveled only a handful
of complete human genomes, all financed by
governments, foundations and corporations
in the name of medical research.
But while money may buy a full readout of
the six billion chemical units in an individual’s
genome, biologists say the superrich will
have to wait like everyone else to learn
how the small variations in their sequence
influence appearance, behavior, abilities,
disease susceptibility and other traits.
Biologists have mixed feelings about the emergence of the genome
as a luxury item. Some worry that what they have dubbed “genomic
elitism” could sour the public on genetic research that
has long promised better, individualized health care for all.
But others see the boutique genome as something like a $20 million
tourist voyage to space — a necessary rite of passage for
technology that may soon be within the grasp of the rest of us.
Scientists say they need tens of thousands of genome sequences
to be made publicly available to begin to make sense of human
variation.
Mr.
Stoicescu, who wants to create an open database of genomic information
seeded with his own sequence, hopes others will soon join him.
2008 February. Statistical
Challenges in Genomics. by Kathleen
M. Wong, ScienceMatters@Berkeley ...Called
a DNA microarray, it is a miniature laboratory
on a chip. In a single experiment it can deliver
a detailed snapshot of the thousands of genes
and proteins interacting in an organism, whether
bacterium or human.For biologists, DNA microarrays
have been boon and curse alike. Researchers
routinely use these assays to monitor gene
expression patterns in cells from cancer patients,
with the aim of deriving better diagnosis
and treatment strategies for the disease.
They can now obtain unprecedented insights
into the activities of genes and cells with
a minimum of experimental effort. At the same
time, they are struggling to make sense of
the tidal wave of data that ensues. "Each
microarray experiment yields thousands and
thousands of measurements for just one person," says
Sandrine Dudoit, a Berkeley professor of Biostatistics
and Statistics. "Microarrays
and other high-throughput biological assays
are raising challenging statistical design
and analysis questions and are a driving force
for our discipline. The scale and complexity
of the data are unprecedented and far greater
than traditional methods allow you to handle." ...Dudoit
specializes in developing statistical and
computational methods to analyze and comprehend
the mind-bogglingly large and intricate datasets
generated by high-throughput biotechnologies
such as DNA microarrays. ...She develops statistical
methods to uncover relationships among a patient's
entire genome; demographic and environmental
variables such as age, sex, ethnicity, and
diet; and medical outcomes such as survival
prognosis and response to treatment. ...With
a next generation of DNA sequencing machines
entering the scene, we are facing new and
even greater statistical and computational
challenges," Dudoit says. "You feel
like your work really matters; it's being
applied immediately, with the goal of elucidating
fundamental scientific questions and improving
public health."
2008 February. Gene
escapes to weeds from engineered canola. Union
of Concerned Scientists newlstter. A
recent study found that canola plants in
Quebec, Canada, that were genetically engineered
for herbicide resistance have interbred
with a weed called wild mustard, producing
hybrid plants that are resistant to the herbicide
glyphosate. The herbicide-resistance gene
persisted over five generations and spread
from the hybrids into the mustard weeds, in
spite of the fact that no herbicide was applied
to the area. The event is significant for
two reasons. One, it is the first known escape
of a gene from a commercialized genetically
engineered crop into a weed. Two, because
canola is a major crop, covering an estimated
two million acres across Canada, it is likely
that gene escape has occurred at multiple
sites in addition to the few that were monitored.
The event echoes the escape of a gene for
glyphosate resistance from field trials of
bentgrass into wild relatives (see our previous
story).
Inadequate confinement of engineered crops
may harm ecosystems in some circumstances
and may hasten the development of herbicide-resistant
weeds. Read the abstract describing
the study in the scientific journal Molecular
Ecology.
January 2008. The
Copy Machine of the Cell
by Kathleen M. Wong.
Excerpt: There comes a
time in many a cell's life when it feels the
need to reproduce. But
before it can split into two, it must fashion
a second set of genetic
instructions to pass on to the new cell.
When Berkeley professor of biochemistry and
molecular biology Mike
Botchan first began studying chromosome copying,
basic questions
about the process remained unknown. He wanted
to understand how and
where DNA replication began. Over the past
three decades, Botchan has
been instrumental in piecing together the
story of what he calls "the elaborate
dance of replication."
Botchan began by studying viruses, the simplest
of all life forms.
These microbes contain relatively few genes
in their chromosome,
borrowing much of the machinery needed to
duplicate their own DNA
from host cells. ...To decipher the string
of events required to
start replication, Botchan mapped the initiation
site-a place on a
chromosome where replication begins-in a virus.
He found that a
certain DNA sequence attracts a virus protein
involved in replication
initiation. Only then can the virus helicase,
which unwinds and
separates the strands of DNA, bind to the
chromosome and start
unraveling DNA....
But do more complex organisms, such as insects
and humans, copy their
DNA in a similar fashion? To find out, Botchan
studied a case of
unchecked DNA replication in fruit fly embryos.
The cells that go on
to form the fly's eggshell duplicate certain
sections of their DNA with astonishing rapidity,
initiating replication at many sites at
once. In these cells, Botchan found and characterized
a complex of proteins that finds the initiation
site and prepares the chromosome so that a
core replication machine can be assembled
there. The core replication machine includes
a six-protein complex used at all DNA
replication sites. Several of these proteins
form a pinwheel
structure that encircles DNA, while another
links to the polymerase enzyme that "reads" the
sequence. In cells actively copying their
DNA, all of these proteins are located right
on top of one another.
...Botchan's work, along with research by
Berkeley biologists Eva
Nogales and James Berger, helps prove that
DNA replication has
changed very little across evolution. "All
three kingdoms of life
share a basic core machinery that assembles
on DNA and prepares it
for unwinding," Botchan says. Organisms
ranging from E. coli to fruit
flies, they find, have nearly identical chromosome
copying methods,
cementing the relationship of all life forms
back to that first
ancestral cell.
October 2007 The
Mathematician and the Genome.
By Kathleen M. Wong, ScienceMatters@Berkeley.
Excerpt: ...The completion of the Human Genome
Project in 2001 was hailed as a major breakthrough
in science. For the first time, humans could
look at their DNA and discover traits ranging
from their propensity to alcohol addiction
to the likelihood that their children will
have blue eyes.
...Since then, scientists have added the rat,
cow, chicken, dog, and even platypus to the
list of creatures whose genes have been read
like a biochemical book. Each species has
shed new light on the structure and function
of our own genetic code.
Lior Pachter has been at the forefront of
these new genomic analyses. Officially a UC
Berkeley professor of mathematics and computer
science, Pachter considers himself a mathematical
biologist. He uses the power of mathematical
modeling and statistics to evaluate the vast
quantities of data in DNA.
...Pachter likens genome studies to recreating
plans for an existing building. "Until
now, we've just been labeling the parts, the
doorknobs and windows. Only recently have
we started to ask about the function of the
parts, and how these functions are related
to each other."
...In addition to sequence data, a profusion
of other genetic information is now flooding
the field. Measurements of gene expression
in different tissues, ways to measure gene
variations between individuals, and other
information can all help make sense of how
our DNA makes us who we are. "Mathematics
and statistics provides a good means for synthesizing
the data in a reasonable way," Pachter
says.
Just this year, Pachter began collaborating
on the Human Microbiome Project. This new
initiative from the National Institutes of
Health seeks to analyze the microbial flora
that lives in and on the human body. Scientists
estimate that each person carries around 10
times more bacterial than human cells, species
ranging from helpful gut microbes to pathogens
like streptococci. The project will generate
a jumble of gene fragments from both known
and new species. Pachter's role is to help
determine the rough number of creatures represented
in the mix.
"It's fun for me that I can combine both
mathematics and biology and participate in
these major enterprises," Pachter says. "The
best thing is, I get to do a lot of beautiful
math to go along with it."
26 June 2007. Human
DNA, the Ultimate Spot for Secret Messages (Are Some There Now?). The New York Times. ByDennis Overbye.
Excerpt: … Using the same
code that computer keyboards use, the Japanese group, led by
Masaru Tomita of Keio University, wrote four copies of Albert
Einstein’s famous formula, E=mc2, along with “1905,” the
date that the young Einstein derived it, into the bacterium’s genome,
the 4.2-million-long string of A’s, G’s, T’s
and C’s that determine everything the little bug is and
everything it’s ever going to be. The feat, they said
in a paper published in the journal Biotechnology Progress,
was a demonstration of DNA as the ultimate information storage
material, able to withstand floods, terrorism, time and the
changing fashions in technology, not to mention the ability
to be imprinted with little unobtrusive trademark labels — little “Made
by Monsanto” tags, say. In so doing they have accomplished
at least a part of the dream that Jaron Lanier, a computer
scientist and musician, and David Sulzer, a biologist at Columbia,
enunciated in 1999. To create the ultimate time capsule as
part of the millennium festivities at this newspaper, they
proposed to encode a year’s worth of the New York Times
magazine into the junk DNA of a cockroach. “The archival
cockroach will be a robust repository,” Mr. Lanier wrote, “able
to survive almost all conceivable scenarios.” …
June 2007. Looking
Deep, Deep Into Your Genes.
OnEarth, NRDC. by Laura Wright. Excerpt:
Discoveries about the impact of the environment
on our DNA could revolutionize our concept
of illness. ...Although some diseases are
inherited through a single genetic mutation
-- cystic fibrosis and sickle cell anemia
are examples -- the classic "one gene, one disease" model
doesn't adequately explain the complex interplay
between an individual's unique genetic code
and his or her personal history of environmental
exposures. That fragile web of interactions,
when pulled out of alignment, is probably
what causes many chronic diseases: cancer,
obesity, asthma, heart disease, autism, and
Alzheimer's, to name just a few....
...The completion of the Human Genome Project
in 2003 armed scientists with a basic road
map of every gene in the human body, allowing
them to probe more deeply into the ways our
DNA controls who we are and why we get sick,
in part by broadening our understanding of
how genes respond to external factors.
...In 2001, Jennifer Sass, a neurotoxicologist
and senior scientist at the Natural Resources
Defense Council (NRDC), who was then a postdoctoral
researcher at the University of Maryland,
designed an experiment that included the use
of microarrays and other molecular tools to
figure out how, exactly, mercury was interfering
with both our nervous and immune systems.
...The findings of Sass, Silbergeld, and others
indicate that mercury might play a role in
the development of diseases involving immune
system dysfunction. These diseases perhaps
include autism ... but also the spate of autoimmune
disorders that we can't fully explain, from
Graves' disease and rheumatoid arthritis to
multiple sclerosis and lupus.
"Do we need to reevaluate our fish advisories?" Silbergeld
asks. "Are our regulations actually protecting
the most sensitive people?" We target
pregnant women and children because we've
presumed that mercury's neurotoxic effects
are most damaging to those whose brains are
still developing. Sass and Silbergeld's findings
don't contradict that assumption, but they
do suggest that there might be other adults
who are far more vulnerable than we'd realized
-- who simply can't tolerate the more subtle
effect the metal has on their immune system
because of a peculiarity in their genetic
makeup. Designing fish advisories for those
people, whose sensitivities are coded in their
DNA, is a challenge we've never tackled before....
23 May 2007. Study:
Climate Change Could Harm CropsBy
THE ASSOCIATED PRESS. Excerpt:
ROME (AP) -- ...During the next 50 years,
more than 60 percent of 51 wild peanut species
analyzed and 12 percent of 108 wild potato
species analyzed could become extinct because
of climate change, according to a study released
Tuesday by the Consultative Group on International
Agricultural Research. Surviving species would
be confined to much smaller areas, further
eroding their capacity to survive, the report
said. The study looked at the distribution
of various species and predicted their ability
to survive based on current and projected
climate data for 2055. Farmers and researchers
often depend on wild plants to breed new varieties
of crops that contain genes for traits such
as pest resistance or drought tolerance, and
that reliance is expected to increase as climate
changes strain the ability of crops to continue
to have the same yields as now, the group
said in a statement. In recent years, genes
found in wild relatives have helped develop
new types of domesticated potatoes that can
fight devastating potato blight and new varieties
of wheat more likely to survive droughts,
the statement said. ''There is an urgent need
to collect and store the seeds of wild relatives
in crop diversity collections before they
disappear,'' said Andy Jarvis, an agricultural
geographer who led the study. ''At the moment,
existing collections are conserving only a
fraction of the diversity of wild species
that are out there.'' ....Consultative Group
on International Agricultural Research: http://www.cgiar.org
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