IT COULD be a case of mass delusion. But plant geneticists say that before
the decade is out, they could understand absolutely everything about how plants
tick. Everything—every gene, every molecule, in every cell. And the key? A
humble weed called Arabidopsis, or thale cress. Crack the weed, they
say, and the secrets of the plant kingdom will be ours.
The plan is nothing if not ambitious. Launching the “2010 Project” earlier
this year, these plant geneticists declared their intention to work out the
function of every one of Arabidopsis’s 25,000 genes.
The first question you might want to ask the project’s fans is “Why?” And the
answer is not “because it’s there”. By identifying each gene function and
tracking every chemical pathway the researchers hope to have “a blueprint for
understanding how plants are built and how to improve them”, says the 2010
Project manifesto. Flowering plants have evolved relatively recently, over the
past 150 million years, and thus are all so closely related that most of the
genetic building blocks and switches discovered in Arabidopsis will be
directly applicable to crop species
(see Diagram). “I could be wrong, but
I personally believe there are not going to be a lot more genes to discover in
other plants,” says Chris Somerville of the Carnegie Institute of Washington’s
Department of Plant Biology at Stanford University.
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The aim is to produce a massive database of each gene and protein in
Arabidopsis so scientists can manipulate plants more easily and herald a
new green revolution. It might even help us understand better how human genes
work.
It sounds like one heck of a challenge. But the thing is, they just might do
it.
For a start, they’ve already got the genome. Publication of the gene
sequences of the last of the plant’s chromosomes is imminent—marking the
culmination of a six-year international collaboration that spanned the US,
Europe and Japan.
It’s a remarkable achievement. But can the Arabidopsis enthusiasts
really decipher how the entire plant functions by 2010? “I think we’ll deliver,”
says Somerville, an early torch-bearer for Arabidopsis. It may sound
wildly optimistic, he agrees, but no more so than sequencing the plant’s genome
seemed 10 years ago. Arabidopsis has rather a modest genome
(see Diagram),
but it still has twice as many genes as the much-studied fruit
fly Drosophila. Back in the dark ages of genomics, sequencing even the
cress’s comparatively concise package of genes seemed unimaginable.
“Try to think back to what people were doing in 1990,” says Somerville. “It’s
easy to forget that, a decade ago, it took six post-doc years to isolate a plant
gene. Now my lab isolates genes in just five person-weeks.” He and his
colleagues are counting on more of the same sort of progress to hurry their new
project along.
To win over the sceptics, Elliot Meyerowitz of Caltech offers an analogy. “A
colleague of mine worked out that a yeast cell and a 777 airplane have the same
number of parts, the same level of complexity. The airplane’s design is on a
computer database, so in principle it should be possible to do the same for the
cell.” Of course, he adds with a chuckle, the cell has packed all that
complexity into a sphere just 5 micrometres in diameter, and can reproduce
itself to boot. And Arabidopsis has millions of cells that are at least
as complex as those of yeast.
It may be merely a small, inedible member of the cabbage family, but thale
cress is also a gene jockey’s dream subject. For a start, you don’t need fields
to grow it in—”A real boon,” says Gloria Coruzzi of New York University,
“when, like me, you work in the middle of Manhattan.” Easy to grow from seed, it
happily completes its life cycle in just six weeks. The plants are
self-fertilising and produce thousands of seeds, streamlining the production of
interesting mutant lines. To date, 50,000 different variants are stored in
“resource centres” at the University of Nottingham in Britain and at Ohio State
University in the US.
And there’s an even bigger bonus: its distinguished genetic ancestry.
Arabidopsis may look insignificant, but it clearly knows a thing or two
about survival. Shrewdly, it favours open, dry places, such as roads and
railways, walls and wasteland. As a result, the species has staked out an empire
that stretches from Europe to East Asia and Africa, from the Arctic Circle to
the equator. Introduced to other climes, it is now doing well in North America,
South Africa and Australasia and is on the way to becoming ubiquitous, says
British botanist Tim Rich. A truly global plant promises to become the plant to
stand for all plants.
Already, what has been achieved “just leaves your mouth open”, says
Meyerowitz. For example, Detlef Weigel of the Salk Institute for Biological
Studies at La Jolla, California, and his colleagues used Arabidopsis to
find the genetic switches that turn on flowering. By flipping the same switches
in poplar trees, they were able to force the trees to flower when just three
months old. They’d turned the poplar into an annual plant, bringing trees within
the grasp of plant breeders for the first time. Once breeders have managed to
breed, say, a tree that’s easier to pulp for paper production, they can undo the
genetic tinkering and end up with trees that flower normally and bear no remnant
of genetic modification.
But there’s more. Arabidopsis has genes that code for 300 membrane
signalling proteins called transmembrane receptor serine/threonine kinases.
Animals don’t have these proteins and no one knows what any of them does. All
the same, their existence implies a massive and hitherto uncharted
communications network, linking cells together and coordinating their response
to the environment. Evolution has evidently equipped plants with a variety of
unique signalling pathways.
More often, plant pathways are “an intriguing montage” of similarity and
difference to animals, says Joanne Chory of the Salk Institute. After all,
almost two billion years have passed since plants, animals and fungi diverged
from a common, single-celled ancestor. “Plants have evolved distinctive
strategies for being multicellular,” explains Mike Bevan of the John Innes
Institute in Norwich, “so studying Arabidopsis will shed a lot of light
on living organisms as a whole.”
Occasionally, Arabidopsis may even be a good tool for studying
humans. In some genes, for reasons that remain obscure, the plant seems to have
more in common with people than with yeast, bacteria, nematode worms or fruit
flies. “Some Arabidopsis genes show a very high similarity to
comparable human genes, more than is the case with fruit flies or nematodes,”
says Bevan. In a few instances at least, plants and humans seem to share ancient
molecular mechanisms that appear to have undergone modification during the
evolution of invertebrates. He points to surprisingly close homologues between
humans and Arabidopsis in genes involved in DNA damage repair and
transport, for instance. Already, we know that several hundred Arabidopsis
genes are “very close homologues” to human genes implicated in
a range of diseases, he says. “Such discoveries mean that it might be possible
to study some aspects of human disease genes using the technical advantages of
Arabidopsis,” he suggests.
Still, the prime pay-off will be in understanding what makes plants tick.
Chory suspects, for example, that plant communication networks are probably
better attuned than animal systems to sensing features of the outer world such
as light, temperature and water. We already know that plants have the richest
array of light-sensing mechanisms of any group of organisms.
Arabidopsis comes equipped with the genetic wherewithal to make
photoreceptors that can discriminate an extraordinary range of light
intensities, wavelengths and day lengths, Chory reports.
The biggest challenge, though, is the 12,000-odd genes that have no known
function. “The really big idea of the project,” says Somerville, “is that it’s
OK to work on genes when we don’t know what the heck they’re doing.” In the
traditional way of going about things, he explains, “a researcher would be
interested in some problem, identify a few genes involved in that process, and
then try to convince a funding body to give them money. We’re proposing
something radically different.”
Specifically, they need $500 million over the next decade to support
specialist labs to work through the whole genome systematically, finding out
where and when genes are expressed, mapping all interactions between proteins,
and pinpointing where all the proteins in each cell are found. With these labs
in place, the researchers feel they have a real chance of unravelling the
function of all the weed’s genes.
All lit up
One of the key tasks will be to identify the “expression pattern” for each
and every Arabidopsis gene—that is, to pinpoint exactly which
cells manufacture each gene’s protein product, and at which stages of the
plant’s life. Rapidly evolving technologies could do the job, such as those that
highlight active genes via special fluorescent markers that function as
“reporter” genes, glowing whenever the gene is active. “You hook up a promoter
to a reporter gene such as green fluorescent protein,” says Coruzzi. “Do that
systematically, for each of Arabidopsis’s 25,000 genes, and you will
really transform every individual lab’s ability to understand gene function.”
Comprehensive microarray chips—another window into gene
expression—will be on the menu, too.
The researchers also aim to create mutants for every gene in the genome,
using a variety of techniques such as “gene traps”. These are engineered
reporter genes that are linked to “jumping genes”, or transposable elements,
that can insert themselves at random around the genome, says Rob Martienssen,
who is applying the technique to Arabidopsis at Cold Spring Harbor
Laboratory near New York. The technology, developed in mice and fruit flies,
provides a powerful way of creating mutations in specific genes and then
figuring out their effects. Because the reporter adopts the same pattern of
expression as the gene into which it is inserted, it “traps” the expression
pattern as well as inactivating the gene. “This is a big advantage,” says
Martienssen. “It means you can study the expression of even a lethal
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The Arabidopsis researchers intend to create a “library” of plants,
each of which carries the reporter inserted into a different gene. Such a prize,
which should be completed in the early stages of the 2010 project, would enable
investigators to inactivate genes one by one and then puzzle out their function.
This will enable researchers to establish links between gene sequence and
function across all plant genes, and then feed their results into a
sophisticated database. “This resource will make the computer the most powerful
tool available to geneticists, replacing conventional laboratory techniques,”
says Martienssen.
Eventually, the Arabidopsis community wants to create a “virtual
plant”. Visit its four-dimensional database in 10 years’ time, and you’ll be
able to click on the image of a growing plant and ask to see which genes are
doing what in any one of the plant’s millions of cells. You will even be able to
play God. Turn up the light and witness—molecule by molecule—how the
plant’s photosynthetic machinery reacts to the rain of photons. Deliver a
drought and watch plant molecules respond to the stress. Unleash a murderous
pathogen and look on as new genes are recruited in the plant’s defence.
The practical pay-off of all this work will be immense, says Joe Ecker of the
Salk Institute. Agronomists keen to boost a crop’s resistance to a viral
disease, say, could work out the genetic manipulation in Arabidopsis,
then apply their knowledge to the crop. In a sense, Arabidopsis is like
a sculptor’s clay model: easy to work with while you’re struggling with the
concept, then you can go back to the marble.
Bigger and better
Or you could think of Arabidopsis, Bevan suggests, as the “foundation
scaffold” that scientists need before they can scrabble around and modify the
edifice of another plant’s genome. The refurbishments on the drawing board are
legion—everything from bigger, more nutritious grains of wheat, maize and
rice, to crops that will grow despite drought, frost or a plague of insect
pests.
“For the first time we will be able to very precisely manipulate the genetic
properties of plants for the good of mankind,” he says. Ecker claims that as
plant genetic modification becomes a highly predictable science, genetic
engineers will even be able to predict the environmental consequences of
releasing genetically modified crops. At last, we will understand exactly how a
plant will respond in any particular environment, he argues. One of the
uncertainties about GM crops is the risk that a gene conferring herbicide
resistance might accidentally escape from the crop and pass into a wild plant,
creating an uncontrollable superweed. Ecker hopes the 2010 Project will discover
just how probable that outcome might be, through a deep understanding of how the
plant genome works. “We would be able to foresee any risks at the ecosystem
level associated with the horizontal transfer of genes from the GM crop to wild
plant species, for instance,” he says.
“Arabidopsis research will have a significant impact on the
well-being of the human race,” agrees Chory. “We need another green revolution
to feed the world’s rapidly growing population, and I don’t see another way to
do it other than by being a lot smarter about what plants do.”
Meyerowitz goes even further: “What is at stake is a much bigger issue than
just engineering a few crops. Plants are the most important things in our
lives,” he says. “They give us the fuel in our cars, the food we eat, the oxygen
we breathe, feedstocks for the chemicals industry and pharmaceuticals—at
least a quarter of all drugs are direct plant products. Even the desk I am
sitting at is made of wood, and when I look out of my window, plants are what I
see. So if we really want to understand the world we live in and how to interact
with it in a sustainable fashion, we’d better understand how plants work.”
Thanks to the Arabidopsis crowd, botany is sexy again. Not long ago,
says Somerville, “the idea of lots of plant biologists working on a useless weed
was regarded as very amusing”. No one’s laughing any longer.
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Further reading:
Arabidopsis: a practical approach, edited by Zoe
Wilson (Oxford University Press, 2000) - http://nasc.nott.ac.uk
- www.arabidopsis.org