Designer Crops. My Intel Core i7 Sanger sequencing in Manila
Frank A. Hilario
February 01, 2009
It takes brains. This is a true story of brains, sequencings, genomes, made-to-order crops. One brain is logical (it´s sequential); another brain is computational (it´s also logical); still another brain is neither (it´s creative, that´s all). To promote science to promote society, we have need of all 3 of them. The first brain I associate with plant geneticists – they feel filled; the second brain I associate with computer experts – they feel content; the third brain I associate with people like me – I feel great!
The good news is that sorghum´s genome has been completely, successfully sequenced; this science coup has been achieved by an international team led by Andrew Paterson, Director of the Plant Genome Mapping Lab, a joint unit of the University of Georgia and Franklin College of Arts & Sciences. It is now reported in the 29 January 2009 issue of Nature, a science journal with an international reputation for quality of content. Quality is in the details. The bad news is that neither quality nor science is exciting news to many.
Should I, a science writer, be excited? Those scientists who reported their success don´t appear to be excited themselves; look at the uninspiring title of their Nature paper: ´The Sorghum bicolor genome and the diversification of grasses.´ My genome is my total DNA sequence, if I understand things right; and no, my own genome doesn´t excite me at all. Paterson is not communicating; it´s all Greek, it´s all grass to me.
But I´m excited about another genome sequencing – mine, leading to my own Designer Crop of course. To address everybody´s business: global warming.
Now, look at the DNA building blocks below for a species I shall not identify at the moment. If you can come up with the genome sequence of this "%1236AAA" DNA set – all the letters of the alphabet are there – then you can design a supercrop that is perfect for the 21st century – amidst problem crops, problem soils, problem local weather, including problem political climates. Since the 1880s, they have had crop circles in England; this is the modern crop circle I have in mind:
1 2 3 6 A A A A A A A A A A A A A A A A A A A A B C C C C C C C D D D D D D D D D D D D E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E F F F F F F F F F F F F G G G G G G G G G G G G G G G H H H H H H H H H H I I I I I I I I I I I I I I I I I I J K L L L L L L L L L L L L L L L L L M M M N N N N N N N N N N N N N N N N N O O O O O O O O O O O O O O O O O O O O O O O O O P P P P Q R R R R R R R R R R R R R R R R R R R R R R R R R R R R R S S S S S S S S S S S S S S S S S S S S S S S T T T T T T T T T T T T T T T T T T T T T T T U U U U U U U W W W W W W W W W W X Y Y Y Y Y Z Z
Can you read my mind? Of course not. That´s the point.
"%1236AAA" is a designer brainteaser. You can´t read between the lines – the lines themselves don´t tell you anything, except that they are strings of letters all derived from the English alphabet. Do you realize Paterson & Co couldn´t have sequenced the sorghum genome with superfast computers without the slow English alphabet?
Now you´re getting a good idea how (almost) impossible it is to sequence anybody´s genome: human being, mungo bean, grain or sweet sorghum. It takes human brains and computer brains to sort things out superfast, to read the instructions for life (DNA) and, even with all that, it takes years. It took Paterson & Co 3 years to assemble and annotate the genome of sorghum (phytozome.com). And that was fast.
"%1236AAA" is a designer complexity. You can´t decipher it. What you have seen is only 1 set of codes, and it is made up of 317 letters & other characters of the English language – anyway, I challenge you to make sense of it, to read the message of a crop.
That alphabet soup is my creative reaction to the critical news that the genome of sorghum has been completely sequenced (see ´Scientists publish complete genetic blueprint of key biofuels crop´ (David Gilbert, 29 January 2009, innovations-report.de). Not only have Paterson and his scientists published the sequence but they have analyzed the complete genome of sorghum; the scientists belong to the JGI, the Joint Genome Institute of the US Department of Energy and several partner institutions (chinaview.cn).
There are 2 varieties of sorghum; grain sorghum is grown for the grain, sweet sorghum for the sugar. Sweet sorghum is my favorite crop. ´Sorghum´s importance is enormous,´ says Paterson, leader of the genome team (Stephanie Schupska, 29 January 2009, eurekalert.org). That´s sweet.
But I´m not sure I´m clear what genome sequencing is all about. The Human Genome Project website tells me that genome or DNA sequencing is the process of determining the exact order of the chemical building blocks (called nucleotides or bases) (ornl.gov), in the order of the many As, Cs, Gs and Ts that make up an organism´s DNA; the human genome has 3,000,000,000 of these genetic letters (GNN, genomenewsnetwork.org). A genome is a set of all the genes a species has in its chromosomes. The human genome has 50,000 to 100,000 genes (cccoe.net); the sorghum genome has 30,000 genes, typical of grasses (Dan Rokhsar, Xinhua as cited). As Gilbert puts it (source cited), genome sequencing is ´a highly challenging computational problem.´ The numbers awe me, not excite.
In other words, now they can read the DNA of sorghum as if it were a book, as in fact, scientists call DNA the ´book of life´ (news.bbc.co.uk). DNA reading must be boring!
That´s why I thought of a virtual designer challenge. And so, as I will show you in just a moment, you can read my "%1236AAA" sorghum conundrum as if it were marquee, scrolling screen messages in plain English, no words high-faluting.
Wait, whom do we owe the successful DNA sequencing of sorghum? These people, all 45 of them listed as co-authors of the Nature paper (cited earlier); the long list shows how exhaustingly detailed and terribly difficult the job was that it needed all their brains:
Andrew H Paterson, John E Bowers, Remy Bruggmann, Inna Dubchak, Jane Grimwood, Heidrun Gundlach, Georg Haberer, Uffe Hellsten, Therese Mitros, Alexander Poliakov, Jeremy Schmutz, Manuel Spannagl, Haibao Tang, Xiyin Wang, Thomas Wicker, Arvind K Bharti, Jarrod Chapman, F Alex Feltus, Udo Gowik, Igor V Grigoriev, Eric Lyons, Christopher A Maher, Mihaela Martis, Apurva Narechania, Robert P Otillar, Bryan W Penning, Asaf A Salamov, Yu Wang, Lifang Zhang, Nicholas C Carpita, Michael Freeling, Alan R Gingle, C Thomas Hash, Beat Keller, Patricia Klein, Stephen Kresovich, Maureen C McCann, Ray Ming, Daniel G Peterson, Mehboob-ur-Rahman, Doreen Ware, Peter Westhoff, Klaus FX Mayer, Joachim Messing, Daniel S Rokhsar.
(Aside: I´ve been Editor in Chief of quite a few technical publications for the last 33 years I know that 45 people working together can´t write a single sensible science paper! Would you believe 3? The long list is a not-so-subtle acknowledgment of contributions of people to the whole project. The problem is how to cite the authors in Literature Cited in your paper when the number of authors is longer than the paper itself.)
So they have sequenced the DNA of sorghum; why is that important? Red Orbit says (28 January 2009, redorbit.com):
The researchers are hopeful that the results might lead to ways of creating even more drought-tolerant types while providing a blueprint for developing, through breeding or genetic engineering, improved forms of other crops such as corn.
They owe their huge accomplishment to the genius of Frederic Sanger who first thought of sequencing the genome about 25 years ago; to give due honor, today, the art and science of sequencing DNA is known as Sanger sequencing (Edmund Pillsbury, bioinfo.mbb.yale.edu).
ICRISAT, the International Crops Research Institute for the Semi-Arid Tropics, based in India, is 1 of 21 institutions that participated in the Sanger sequencing of the sorghum genome. Not surprisingly, it has positively and strongly reacted to the news. Director General and Team Captain of ICRISAT William Dar tells me that, from the point of view of ICRISAT, the Sanger sequencing is ´a monumental development which will impact on and enhance our breeding of sorghum varieties adapted to changing climate, abiotic and biotic stresses.´ That is to say, ICRISAT is going to come out with sorghums that grow well considering global warming and, among other things, considering pests, diseases, soil nutrient deficiencies, waterlogging, drought. Especially drought. Knowledge on the DNA sequences ´will speed up development of resilient sorghum varieties.´
With 34,496 gene models of sorghum having been inventoried, Dar says, this opens to great possibilities in breeding. For instance, once some sorghum genes have been predicted or identified for drought tolerance, these genes can be used in genetic engineering to develop drought tolerance even in maize, a species related to sorghum, as well as in other cereals, such as rice. If you can´t fight them, tame them. Design crops that can best stand drought. Designer Maize. Designer Rice.
How about improving sorghum itself? Designer Sorghum. ´Identification and understanding of genes involved in C4 pathways should be useful in manipulating fuel production of sorghum,´ Dar says. ´Fuel´ here refers to ´biofuel´ or ethanol from either or both sorghum grains and stalks. Also, ICRISAT is looking into the possibility of breeding other sorghum varieties with high content of cellulose as an alternative source of renewable fuel for cars, buses, trucks, tractors, including airplanes. (I´ll talk about ´C4 pathways´ in a little while.)
Already, sorghum has many vitamins (ACP, fao.org). Don´t forget, Dar says, that the sorghum grain has high levels of iron (>70 ppm) and zinc (>50 ppm). Once they have identified candidate genes, they can be genetically manipulated to increase iron and zinc contents in sorghum and other cereals to help reduce malnutrition worldwide. From A to Zinc.
There´s more where it comes from. Paterson himself says that the wild relatives of sorghum can survive with even less water and resist even more pests and diseases, and the genes for these can be transferred to the cultivated sorghum (Schupska, source cited). Designer Sorghum. With genetic engineering, hopefully now you can pester all those pests.
Now I go back to my "%1236AAA" puzzler. Since this genius hardly understands the concept of Sanger sequencing himself, I thought of trying to explain it to myself by coming up with a metaphor. Yes, "%1236AAA" is a metaphor. I´m coming up with a virtual sequencing.
Since "%1236AAA" is composed of single letters and other characters that by themselves are unreadable except if they are linguistically related one way or the other so that they become understandable, and since combinations of characters and letters are processed best by the modern PC (personal computer), I decided to turn to the mechanical brain, the central processor of the PC. And just in time, too. The news of the Sanger sequencing of sorghum appeared on 29 January, and I just happened to have brought home my new PC on that same date on the other side of the globe, which I had ordered last December yet from Prologue Computer Center in Los Baños, Laguna. It had taken 1 month; this Intel PC was slow in coming to the shores of the Philippines, I wonder why. When sequencing genome, processing speed is of the essence; when I´m writing and researching at the same time, 2 processing speeds are of the essence: those of the PC and my brain. I don´t think – I scramble my thoughts. I don´t write – I type, and I type fast. (How fast? I´ll give you an idea: About 2 years ago, someone visited at home and saw me typing on the computer keyboard, and asked, matter-of-factly, ´Are you typing, or are you playing?´ I said, ´Both.´ It´s true.)
Now I have ´the fastest processor on Earth´ – no, I´m not referring to my brain – as I write these lines 30 January, I´m referring to our barely 24-hour old PC, an Intel Core i7 920 @ 2.67 GHz 2.66 GHz with 3 GB RAM Transcend DDR3-133 running on a licensed Windows Vista. I´m a superfast writer, editor, book reviewer, publisher, blogger. Now you know why I bought this superfast PC I´m using right now – I deserve it or, which is the same thing, I want my PC to match my speed. I don´t drive a car; I drive a PC. I´m 69; I used to ride the bike, leisurely. I am a speed demon when it comes to writing, editing, book reviewing, publishing, blogging; I know my speed does not endanger life or limb. Right now I have 5,000 photographs of my own in the hard disk – I want my PC to search through all those folders as fast as the eye can see. The Intel Core i7 is a Designer PC – it was designed for speed maniacs like me. It doesn´t have the supernumerary memory to run an assembler program for Sanger sequencing, but it has my unlimited memory.
I am told the Intel Core i7 has the Nehalem processor, ´the most sophisticated ever built, with new technologies that boost performance on demand and maximize data throughput´ (Intel, source cited). I´m sure the Sanger sequencers understand that. Expect performance to the max. Here´s the PC when you need it most. With the sorghum genome known in proper DNA sequence, we can expect breeding performance to the max. Here´s the DNA when you need it fast.
The J Craig Venture Institute calls the genome ´a jigsaw puzzle´ (GNN, genomenewsnetwork.org). It is, because you have to fit the exact pieces together, and there is only 1 solution. But since the sorghum genome contains 30,000 genes, how on earth can you find the proper Sanger sequence when you can´t really see anything? To help myself understand, I programmed our Core i7 to read this alphabet soup as I have already told you:
1 2 3 6 A A A A A A A A A A A A A A A A A A A A B C C C C C C C D D D D D D D D D D D D E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E E F F F F F F F F F F F F G G G G G G G G G G G G G G G H H H H H H H H H H I I I I I I I I I I I I I I I I I I J K L L L L L L L L L L L L L L L L L M M M N N N N N N N N N N N N N N N N N O O O O O O O O O O O O O O O O O O O O O O O O O P P P P Q R R R R R R R R R R R R R R R R R R R R R R R R R R R R R S S S S S S S S S S S S S S S S S S S S S S S T T T T T T T T T T T T T T T T T T T T T T T U U U U U U U W W W W W W W W W W X Y Y Y Y Y Z Z
You cannot imagine the number of possible combinations among those 317 characters, each one representing a gene. To get an idea, if I used all numbers instead of mostly letters, I can get this possible total sequences (combinations) out of
numbers 1 to 29:
8,841,761,993,739,700,000,000,000,000,000
numbers 1 to 39:
20,397,882,081,197,000,000,000,000,000,000,000,000,000,000,000
numbers 1 to 49:
608,281,864,034,270,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000,000 (48 zeros after 270).
I´m using Calculate in Word 2003 to compute for the total number of combinations; at 1 to 50, Word 2003 tells me, ´!Number Too Large To Format.´
All this I´m sure is a miniscule effort compared to the Sanger sequencing of sorghum, but you and I get the idea.
Out of that "%1236AAA" alphabet soup, I´ll tell you in a little while what our brand-new PC came out with using my brains. First, Intel´s brains.
The Core i7 PC processor is the smarts of Intel that boasts what it calls a combination of ´Turbo Boost Technology´ and ´Hyper-Threading Technology´ – which maximizes performance when you need it. As if to test its computing power, the very first assignment I give to our Core i7 is to read the undisclosed messages from the sequence of codes that begins with "%1236AAA." Does it compute?
Look at what it has come out with in deciphering the genetic blocks of my favorite crop – read it as marquee, endlessly moving messages repeating themselves:
SWEETER THAN SUGAR 16-23% BRIX NEEDS MUCH LESS WATER GROWS IN THE DRYLANDS OF THE WORLD TOLERATES WATERLOGGING TOLERATES HEAT TOLERATES ACID SOILS TOLERATES SALINE SOILS GOOD FOR JAGGERY NO FERTILIZER NECESSARY FOOD FEED FODDER FERTILIZER FUEL FENCE PULP FOR PAPER CLEAN FUEL WITH HIGHER OCTANE RATING NO NEED TO MODIFY ENGINE GROWS QUICK GROWS ANYWHERE SWEET SORGHUM IS GREAT!
Now then, with all that knowledge, you can design the perfect climate crop of the 21st century with these desirable characters:
Sweeter than sugar – 16-23% Brix
Needs much less water – grows in the drylands of the world
Tolerates waterlogging
Tolerates heat
Tolerates acid soils
Tolerates saline soils
Good for jaggery
No fertilizer necessary
Food, feed, fodder, fertilizer, fuel, fence, pulp for paper
Clean fuel with higher octane rating
No need to modify engine
Grows quick
Grows anywhere!
And of course, in the end you will learn that in fact, we already have that Ultimate Designer Crop: Sweet Sorghum. Nature has designed it to be excellent to address public concerns about climatic change as well as private concerns about poor farmers and poor soils.
In other words, I didn´t do any Sanger sequencing at all. I couldn´t recognize a DNA code to save my life. What I really did was come up first of all with the list of the winning ways of sweet sorghum, and then with Word 2003 I separated all the characters individually and sorted them to make what I call the "%1236AAA" genomic building blocks. The true story of my Core i7 just happens to be a perfect decoy to tell this true story of a genome.
So now I can tell you about C4 pathways. Rice is a C3, sorghum is a C4; where sorghum goes is the C4 pathway. A C3 plant is so-called because the first stable product it makes in photosynthesis is a 3-carbon compound; a C4 plant makes a 4-carbon compound first, then goes on its way to manufacture food for itself and man, much more than a C3 plant does. That´s Nature. C3 plants require cooler and wetter climates; C4 plants thrive in hotter, drier environments (answers.com). Like some people you know, rice goes on demanding more resources, while sweet sorghum goes on demanding less and producing more. Rice gets my 3 stars; sweet sorghum gets my 4 stars – no crop is perfect, 5 stars. (A related and helpful metaphor: To thrive, tribes differ as plants do. In the Philippines, you would recognize that the Tagalogs are C3; the Ilocanos are C4.)
C4 crops are hardy and stress-resistant; with knowledge in genome sequence applied in plant breeding, scientists ´could spur 21st century crops´ (29 January, Brandon Keim, greenbio.checkbiotech.org). Red Orbit quotes Joachim Messing, a Rutgers University plant geneticist, one of the authors of the Nature paper, sharing his mind-bending experience with C4 crop sorghum in southeastern Africa (source cited):
You should have seen the maize growing there, how poorly it did, and then see sorghum just across from it standing tall and green and resistant to disease and drought.
Drought is the major environmental factor constraining crop production globally,´ says Andrew Borrell & Co, cropscience.org.au). Other than sorghum, the crops know the plaint of Samuel Taylor Coleridge´s Ancient Mariner: ´Water, water every where / Nor any drop to drink!´ But you have a survivor crop, sweet sorghum. You know why? One reason is that sorghum roots go down beyond 2 meters (Ian Broad & Graeme Hammer, cropscience.org.au), tapping the underground water rising up by capillary action. Not only that – sorghum roots are massive (National Research Council, 1996, books.nap.edu). here is Mother Nature´s intelligence at work: Water seeks its own level – it goes up, up; and the sorghum root knows which side of the soil is wetter – it goes down, down.
Keim says more (source cited):
Developed world farms are already running at maximum capacity, with arable land already planted and the Green Revolution´s fertilizer- and pesticide-based limits reached. Remaining land is often dry and salty, and farms around the world are threatened by weather extremes predicted as consequences of global warming.
In this world, there is a limit to chemical fertilizers and pesticides. Perfect for sorghum, that resilient, tolerant, superior species scientists prefer to call Sorghum bicolor. Almost 2 years ago, I wrote ´On Discovery Sorghum, The Great Climate Crop´ (see ´The Yankee Dawdle,´ 04 February 2007, americanchronicle.com); I believed then, as I express it now, that sweet sorghum is the Compleat Climate Change Crop, the C4 of C4 species. With this Designer Crop, we can design a Green Future for Mother Earth.
Even the independent-thinking Chinese know much about sorghum. They tell us the grains produce as much ethanol per bushel as corn and yet it needs one-third less water. The stalks grow fast, from 8 to 15 feet in 1 season. Sorghum grows well on marginal soils where other crops will stunt or worse, shrivel and shrink (news.xinhuanet.com). It´s a ´failsafe´ crop too (springerlink.com). And it´s a perennial, so it can be ratooned; thus, there is no need for replanting and disturbing the soil after every harvest, thus preventing soil erosion and conserving soil water.
Today, American corn needs twice more water to grow than American sorghum (Schupska, source cited). So, to approximate the projected excellent performance of American sorghum in the primary role of producing more ethanol more efficiently than American corn, which US President George W Bush had insisted as the main source of ethanol for American cars (see also my ´American Corn,´ icrisatwatch.blogspot.com), some American plant breeders are going to transfer the genes of drought-tolerance from sorghum to corn, so that maize will ´over-express the genes´ (Keim´s term) and become drought-tolerant, and eventually become the ultimate corn that it can be. Designer Corn. And they will transfer the genes to other sources of biofuel to produce out of those grasses their Designer Crops: American sugarcane (Designer Sugar), European Miscanthus (Designer Grass), American switchgrass (Designer Switch). This is physical transfer of traits from one crop to another; it is an exception to Mendel´s law of heredity that traits can only be inherited, not acquired. Laws are made to be broken.
It takes brains, yes; it also takes years. In the meantime, I´ll take the road more travelled – I´ll take the Designer Crop of Designer Crops that is here and now: Sweet Sorghum. In the midst of droughts in Africa, Asia, Australia and the Americas, now you know why I have sweet dreams.
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