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Finding dollars in DNA - John Deere

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By Steve Werblow<br />

<strong>F<strong>in</strong>d<strong>in</strong>g</strong> <strong>dollars</strong> <strong>in</strong> <strong>DNA</strong><br />

Genomes are open<strong>in</strong>g the<br />

door to greater productivity.<br />

36 THE FURROW


Almost daily, it seems,<br />

headl<strong>in</strong>es announce that<br />

a new species of plant,<br />

animal, or pathogen has<br />

had its genome sequenced, the code<br />

of each of its genes spelled out and<br />

mapped. Scientists are follow<strong>in</strong>g<br />

those maps to a treasure trove of<br />

<strong>in</strong>formation.<br />

Now they’re sift<strong>in</strong>g through the<br />

data <strong>in</strong> a race to understand those<br />

genes and put them to work <strong>in</strong><br />

improved crops and livestock.<br />

“I don’t th<strong>in</strong>k sequenc<strong>in</strong>g is<br />

go<strong>in</strong>g to be an issue anymore,” says<br />

Kulv<strong>in</strong>der Gill, a wheat breeder<br />

and geneticist at Wash<strong>in</strong>gton State<br />

University <strong>in</strong> the United States. “The<br />

issue is go<strong>in</strong>g to be how to use it.”<br />

Big hurry. In Gill’s lab, graduate<br />

students and post-doctorates are<br />

dropp<strong>in</strong>g tissue samples from<br />

wheat leaves <strong>in</strong>to t<strong>in</strong>y test tubes,<br />

multiply<strong>in</strong>g the genetic material<br />

from the samples so there’s enough<br />

to test, analys<strong>in</strong>g the genes piped<br />

out of each little vial, and search<strong>in</strong>g<br />

for markers that could be l<strong>in</strong>ked to<br />

genetic success. They’re <strong>in</strong> a hurry –<br />

the plants those samples were taken<br />

from are about to flower, and Gill<br />

LEFT: Breakthroughs <strong>in</strong> genetic research<br />

are start<strong>in</strong>g to yield breed<strong>in</strong>g advances.<br />

BELOW: A <strong>DNA</strong> sample on this glass<br />

slide will be analysed by a high-throughput<br />

sequencer that can identify and unscramble<br />

600 billion base pairs – the build<strong>in</strong>g blocks<br />

of genes – <strong>in</strong> a 12-day run cycle.<br />

wants to use their data to select the<br />

most promis<strong>in</strong>g plants to cross.<br />

At another desk, a researcher is<br />

study<strong>in</strong>g the corn genome, look<strong>in</strong>g<br />

for a gene that could confer a new<br />

type of dwarf<strong>in</strong>g characteristic<br />

to wheat. Welcome to breed<strong>in</strong>g,<br />

genomics style.<br />

The tools Gill’s team uses are a<br />

triumph of modern science.<br />

<strong>DNA</strong> is made up of millions of<br />

pairs of just four chemical bases,<br />

labeled A, C, T, and G. That means<br />

every gene is a str<strong>in</strong>g of hundreds<br />

or thousands of those letters. Every<br />

chromosome is a collection of<br />

thousands of genes, along with a<br />

bunch of “junk code” like silenced<br />

genes, old bits of viruses, and other<br />

<strong>DNA</strong> that doesn’t seem to have a role<br />

<strong>in</strong> the organism’s growth.<br />

Some genomes, like those <strong>in</strong> people<br />

and cows, have two copies of each<br />

chromosome, one from mum and one<br />

from dad. Others, like wheat, have six<br />

copies of each. That’s billions of As,<br />

Cs, Ts, and Gs on a gene map. In the<br />

test tube, they’re just alphabet soup.<br />

“Let’s say you took an<br />

encyclopedia, all 26 volumes,” says<br />

Brian Scheffler, who heads the<br />

U.S. Department of Agriculture<br />

Agricultural Research Service’s<br />

Genomics and Bio<strong>in</strong>formatics Unit <strong>in</strong><br />

Stoneville, Mississippi. “Each volume<br />

is a chromosome. Each page is a<br />

gene. Now run them through a paper<br />

shredder – and we’re not talk<strong>in</strong>g<br />

strips, we’re talk<strong>in</strong>g confetti. Then<br />

you have to put it all back together.”<br />

If that’s not challeng<strong>in</strong>g enough,<br />

remember that for plants like cotton,<br />

which has chromosomes from two<br />

different ancestor species <strong>in</strong> every<br />

cell, you’re reconstruct<strong>in</strong>g complete<br />

encyclopedia sets from different<br />

publishers.<br />

That’s why complet<strong>in</strong>g a genome<br />

is such a milestone – a good map<br />

makes sequenc<strong>in</strong>g the next <strong>in</strong>dividual<br />

from that species much easier, and<br />

provides a basis for compar<strong>in</strong>g the<br />

similarities and differences among<br />

chromosomes.<br />

“Resequenc<strong>in</strong>g is like do<strong>in</strong>g a<br />

puzzle and hav<strong>in</strong>g the box top <strong>in</strong><br />

front of you,” Scheffler expla<strong>in</strong>s.<br />

A day’s work. Technology has<br />

gotten faster and cheaper, eas<strong>in</strong>g<br />

the effort. “My Ph.D. thesis would<br />

be about a day’s work for my lab<br />

now,” Scheffler says, add<strong>in</strong>g that<br />

the $100 million rice genome project<br />

completed <strong>in</strong> 2005 would cost about<br />

$2 million today.<br />

That speed and economy propels<br />

Gill’s real-time breed<strong>in</strong>g choices. It<br />

also allows geneticists to analyse the<br />

genotypes of 5,000 to 7,000 U.S. dairy<br />

cows and bulls per month, us<strong>in</strong>g<br />

computerised chips to see which gene<br />

markers are present <strong>in</strong> each animal.<br />

Breeders have spent years correlat<strong>in</strong>g<br />

BELOW: Analys<strong>in</strong>g 60,000 gene markers<br />

<strong>in</strong> a chicken’s genome allows producers to<br />

choose breed<strong>in</strong>g animals <strong>in</strong> 20 weeks rather<br />

than 2 years.<br />

illustration: paul lange<br />

THE FURROW 37


those markers – s<strong>in</strong>gle nucleotide<br />

polymorphisms (SNPs), or “snips”<br />

– aga<strong>in</strong>st thousands of pedigree<br />

records and performance tests.<br />

As a result, they’ve ratcheted up the<br />

accuracy of predict<strong>in</strong>g genetic fitness<br />

<strong>in</strong> dairy cattle to 83 percent us<strong>in</strong>g<br />

computer-analysed “SNP chips,”<br />

compared to a success rate of 35<br />

percent or 40 percent with pedigrees,<br />

says Curt Van Tassell at the USDA-<br />

ARS Bov<strong>in</strong>e Functional Genomics<br />

Laboratory <strong>in</strong> Beltsville, Maryland.<br />

Driven by genomic analysis, the<br />

rate of productivity ga<strong>in</strong> <strong>in</strong> the dairy<br />

<strong>in</strong>dustry is expected to double over<br />

the next few years, he adds. “It’s<br />

already be<strong>in</strong>g felt as the sons of top<br />

bulls are kick<strong>in</strong>g their dads off the<br />

top of the list quickly,” Van Tassell<br />

notes.<br />

Fast and cheap. A SNP chip<br />

analysis of a bull’s genome costs $300<br />

to $500. That’s cheap – compared to<br />

the $50,000 now spent collect<strong>in</strong>g data<br />

on a bull’s daughters – and faster.<br />

“We can identify an up-andcom<strong>in</strong>g<br />

bull essentially from the date<br />

of birth <strong>in</strong>stead of wait<strong>in</strong>g five or six<br />

years like we did <strong>in</strong> the past, when<br />

we had to wait for his daughters<br />

to yield milk<strong>in</strong>g data,” Van Tassell<br />

expla<strong>in</strong>s.<br />

Chicken producers can use<br />

SNP chips, too. At $56 per bird, a<br />

BELOW: Golden capillaries channel<br />

fragments of <strong>DNA</strong> to an analyser. Teased<br />

apart by a gentle electrical charge, they form<br />

a “genetic f<strong>in</strong>gerpr<strong>in</strong>t.”<br />

few thousand birds at a time, the<br />

economics of a 60,000-marker<br />

SNP test are a bit more daunt<strong>in</strong>g,<br />

accord<strong>in</strong>g to poultry and aquaculture<br />

breeder Bill Muir at Purdue<br />

University, Indiana, though genomic<br />

selection has more than doubled the<br />

annual rate of ga<strong>in</strong> <strong>in</strong> the <strong>in</strong>dustry.<br />

“Where this technology has the<br />

greatest potential to br<strong>in</strong>g about<br />

good is traits that are expensive to<br />

measure, difficult to measure, or that<br />

don’t exhibit until later <strong>in</strong> life,” Muir<br />

says.<br />

Feed efficiency, carcass quality, egg<br />

production, or low-heritability traits<br />

like leg soundness are prime targets.<br />

Muir is develop<strong>in</strong>g smaller SNP<br />

chips with markers correspond<strong>in</strong>g to<br />

specific traits like egg production or<br />

feed efficiency. His goal is to br<strong>in</strong>g<br />

the price down to a few <strong>dollars</strong>.<br />

But don’t confuse the success of<br />

SNP chips or marker-assisted<br />

breed<strong>in</strong>g – us<strong>in</strong>g SNPs to track<br />

key bits of <strong>DNA</strong> through the plant<br />

breed<strong>in</strong>g process technology that’s<br />

already yielded blockbuster hybrids<br />

and Clearfield wheat – with a deep<br />

understand<strong>in</strong>g of how genes actually<br />

work.<br />

“We’re try<strong>in</strong>g to decipher all<br />

the <strong>in</strong>formation that’s com<strong>in</strong>g <strong>in</strong><br />

and decide what it means,” says<br />

<strong>John</strong> Soper, vice president of crop<br />

genetics R&D for Pioneer Hi-Bred<br />

International <strong>in</strong> <strong>John</strong>ston, Iowa. “The<br />

scientists work<strong>in</strong>g on this will start<br />

to focus on ‘what is a gene really<br />

all about? What is the recipe for a<br />

38 THE FURROW


esistance gene?’ Perhaps the last<br />

piece of the puzzle, the complex<br />

piece of the puzzle, is start<strong>in</strong>g to<br />

understand how genes <strong>in</strong>teract.”<br />

Scheffler agrees.<br />

“When I did my Ph.D., from 1986<br />

to 1989, science moved forward<br />

one gene at a time,” he says. “Now<br />

we’re ask<strong>in</strong>g the question, ‘what’s<br />

happen<strong>in</strong>g when the whole th<strong>in</strong>g<br />

comes together?’ That’s important<br />

because when you get down to<br />

yield, it’s not just one gene – yield<br />

is multiple genes, multiple levels of<br />

expression.”<br />

Global questions. “Now we can<br />

start pull<strong>in</strong>g th<strong>in</strong>gs apart,” Scheffler<br />

cont<strong>in</strong>ues. “We can start ask<strong>in</strong>g<br />

global questions like, ’when a plant<br />

is experienc<strong>in</strong>g drought, which genes<br />

have an impact on yield?’ We can<br />

start solv<strong>in</strong>g problems we couldn’t<br />

address before.”<br />

Every crop sequenced and every<br />

gene identified br<strong>in</strong>gs all breeders a<br />

step closer to the next advance, adds<br />

Gill.<br />

“Once a gene is cloned <strong>in</strong> rice, it’s<br />

more than likely it will work the<br />

same <strong>in</strong> wheat,” he says. “We are<br />

go<strong>in</strong>g to learn from each other.”<br />

ABOVE: Genomics allows plant<br />

breeders to start manag<strong>in</strong>g crosses <strong>in</strong><br />

the lab or greenhouse, not the test plot.<br />

BELOW: Kulv<strong>in</strong>der Gill of Wash<strong>in</strong>gton<br />

State University says cost-sav<strong>in</strong>g genomics<br />

tools can help breeders develop varieties<br />

with genes ideal for specific regions or<br />

niche crops.<br />

THE FURROW 39

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