agriculture

Elizabeth Pennisi's story about maize genomics is a good reminder for why biology will continue to grow in importance toward our understanding of human history:

With $9.1 million from the Mexican government, Jean-Philippe Vielle-Calzada of the National Laboratory of Genomics for Biodiversity in Irapuato and his colleagues have decoded a native "popcorn" strain grown at elevations above 2000 meters. Although still in more than 100,000 pieces, the sequence has revealed many new genes, he reported. This variety's genome "will be of tremendous value in terms of understanding the evolution of [maize] domestication," he says.

Oh, and if you're interested in biology, consider the potential experiments from this:

Another resource introduced at the meeting will help ... sort out how genes interact. The agribusiness giant Syngenta announced it was making available 7500 lines of corn, each representing a B73 genome with a single piece of DNA bred into it from one of the 25 strains of the Maize Diversity Project. Taken together, the lines incorporate all the genetic diversity of those strains but make it easier to understand the activity of particular genes. The community has long awaited these tools, says Brutnell: "They are really going to revolutionize the way we do genetics."

I'd say. Imagine 7500 twins, all identical except for a unique piece of DNA spliced in from some other person. Except with corn, it's not 7500 twins, its 7500 experimental plots full of twins. Now, see what they all do!

References:

Pennisi E 2008. Corn genomics pop wide open. Science 319:1333. doi:10.1126/science.319.5868.1333

n. b. This is a story about my work on recent human evolution, describing some of the main results and how the work came about. The story refers to my paper (with Gregory Cochran, Eric Wang, Henry Harpending, and Robert Moyzis), "Recent acceleration of human adaptive evolution," which came out in December, 2007.

Like most good stories in biology, this one begins with Darwin. Darwin was always very interested in animal breeding, which he considered the best analogy for the process of natural selection. Of course, if you're breeding livestock and want to select for some characteristics, it is important to select from as large a herd as possible, because large populations have more variation in them. Darwin recognized this as an important condition for natural selection, which relies on sufficient variation in natural populations.

[A]s variations manifestly useful or pleasing to man appear only occasionally, the chance of their appearance will be much increased by a large number of individuals being kept.... Hence, number is of the highest importance for success.

These words from the Origin, "number is of the highest importance for success" were influential.

This is a quick review of the research, based on a presentation I gave earlier this year. It is not complete, and glosses a number of very important details. A close reader looking for how to do genomics would be better served reading the actual research paper. Here, I'm trying to express the science for everyone else.

By 1930, R. A. Fisher picked up Darwin's idea about numbers, predicting that evolution in large populations could be faster than in small populations. However, this is not in all circumstances, but only where the number of new adaptive mutations is quite small -- in other words, where evolution is "mutation-limited":

The great contrast between abundant and rare species lies in the number of individuals available in each generation as possible mutants.... The importance of the contrast lies with the extremely rare mutations, in which the number of new mutations occurring must increase proportionately to the number of individuals available.

A long history of research in plant genetics (corn breeding), microbial chemostat experiments, and the examination of pesticide resistance in insects support Fisher's concept. For example, flies subjected to low doses of pesticide in the laboratory tend to acquire very complicated patterns of resistance -- involving slight changes in many different genes. These usually aren't transmitted perfectly and often have fitness costs; it's a very imperfect adaptation. But if pesticide is sprayed over a large area, flies sometimes appear very quickly with a single mutation that confers very complete resistance. Here, the very advantageous resistance mutation is incredibly rare -- it only occurs in maybe one in a billion flies. It would never occur in the small laboratory population.

Our growing population

Human populations have been growing rapidly during the last 50,000 years or so. That increase began around the time of the Upper Paleolithic -- that's documented by archaeological evidence. There was a later massive increase during the Neolithic. This agricultural transition actually was quite heterogeneous: earlier in West Asia and China, later in Europe, and then later still in subsaharan Africa. Last, we have within the last few hundred years seen a massive increase in numbers associated with industrialization and globalization of technology.

One day a couple of years ago, Greg Cochran and I were talking about brain evolution. You have to understand, this is long before we knew about any of these genome scans -- they hadn't come out yet. One of the main mysteries of human brain evolution is why it happened apparently gradually for such a long period of time. It is one of the best cases of evolutionary gradualism. But this is a problem, because directional selection would have too be too weak to take such a long time. Now, we know that brain size is constrained in two directions -- larger brains cost more energy to maintain, but smaller brains come with some functional disadvantages. So this creates a situation where new variants that satisfy both constraints -- costing little energy, or making great improvements in brain function -- must be very rare. It should be mutation-limited.

I remember very well, that at precisely the same moment, we both realized -- "Hey, maybe this great increase in human population size made a difference!" Because as we'll see later, the pattern of change in brain size really changed when populations started to get really big.

You see, this is one of those very rare cases where the theory preceded the data! It is quite simple; the rate of mutations in a population is a linear product of the rate per genome and the population size.

Not all mutations are advantageous, and not all advantageous mutations will be fixed. The vast majority are lost. If a mutation has a selective advantage, then the chance that it will proceed toward fixation (and attain high frequency) is 2s -- "s" here is the fitness advantage. That means that 90 percent of new mutations with a 5 percent fitness advantage are simply lost.

The most beneficial mutations are very rare; it is much more likely that a new mutation will be weakly selected. This is another aspect of selection that has been well-known since Fisher. So the chance of fixation increases with s, but the likelihood of the mutation decreases with s -- in fact, the number decreases exponentially as selection is stronger and stronger.

If you put all these together, you can predict how many selected changes you should see in a population that has been growing in size. This tells us the number of new adaptive mutations that should come into the population each generation. It is still linear with population size -- a larger population should have more mutations in precise proportion to its size.

Still, a very small fraction of the mutations in any given population will be advantageous. And the longer a population has existed, the more likely it will be close to its adaptive optimum -- the point at which positively selected mutations don't happen because there is no possible improvement. This is the most likely explanation for why very large species in nature don't always evolve rapidly.

Instead, it is when a new environment is imposed that natural populations respond. And when the environment changes, larger populations have an intrinsic advantage, as Fisher showed, because they have a faster potential response by new mutations.

From that standpoint, the ecological changes documented in human history and the archaeological record create an exceptional situation. Humans faced new selective pressures during the last 40,000 years, related to disease, agricultural diets, sedentism, city life, greater lifespan, and many other ecological changes. This created a need for selection.

Larger population sizes allowed the rapid response to selection -- more new adaptive mutations. Together, the the two patterns of historical change have placed humans far from an equilibrium. In that case, we expect that the pace of genetic change due to positive selection should recently have been radically higher than at other times in human evolution.

Finding selection in the genome

Now, it comes to a problem of how we can see recent mutations that have been selected. A genome scan is based on things that vary, not things that are fixed. So we are looking at some window of frequencies. In our study, that was a window from around 22 to 78 percent.

Before we go too far, it is important to point out that an adaptive gene will be in a window where we can detect it for only a short time -- it spends a long time getting up to an appreciable frequency (here 22 percent, which is our lower ascertainment bound) and a long time going from a high frequency (here 78 percent) to fixation -- this is for a dominant. But it spends only a very short time in the window where we can see it.

And strongly selected genes go through this window quite a lot faster than weakly selected ones.

The importance of this is that we will see genes with different strengths of selection at different ages. Our constraint is that right now all the things we can see are variable -- but some are variable because they originated a short time ago and were very strongly selected, and others are variable because they originated a long time ago, but were very weakly selected.

You can guess, that we expect to see more of the weak ones than the strong ones, because there should be more of them! So the window should give us a view of the strength of selection as well as the number of mutations. If we can estimate the ages of our mutations, then we can predict how many there should be at different strengths of selection, and try to quantify the effect of population size.

Here, we've drawn a graph showing the number of genes in the window, compared with the number that are still variable in the population -- they are on their way to fixation -- but they are outside the window. This is for a growing population, so you see that the number of these genes increases as you get closer to the present.

There are many more that we can't see than the ones we can see -- this is like the tip of the iceberg. That is one aspect of recent selection; these genes are in this intermediate frequency range for a short time, and there will be many more genes that are too rare for us to see with our current methods, but might be very important regionally or locally in some populations.

Based on a model of population growth, we expect to see a big peak corresponding to the period when humans were growing rapidly during the Neolithic. The distribution should plunge down toward the present, because selection would have to be so strong on such a recent mutation for us to see it -- we're talking about 20 percent or more. Those just almost never happen. The true number, remember, is the iceberg under the water -- but we must make predictions about the part we can see.

Linkage disequilibrium and selection

Now, I need to say a few words about how we find these genes when we scan the genome. The International HapMap consists of a list of over 3 million genetic polymorphisms -- SNPs -- taken from a sample of people with ancestry in Northern Europe, West Africa, and East Asia. When we look at a sample of a long stretch of DNA from several people, we will be considering the frequency of many different polymorphisms.

But more important, we have studied whether each polymorphism is linked to the others. As a new positively selected allele increases in frequency in a population, it is initially linked to a wide region including many nearby polymorphisms. This induces a long-distance association among SNPs, which is called linkage disequilibrium.

When we are looking at a stretch of chromosome, what we can observe is that there are areas where recombination seems to be very rare around one SNP -- an in particular where one of the two SNP alleles has almost no recombinant chromosomes, but the other allele appears to have been recombining normally. That kind of mismatch is a strong indication of selection.

I'm not going into the details of that process right now; I'll be posting some real examples of such LD decay analyses later in the week. After applying the analysis, we found more than 3000 in the Yoruba sample, more than 2800 in Europeans, and more than 2300 in Asians.

These numbers are very large -- they make it look like this aspect of evolution, positive selection on new adaptive alleles, has been going very fast. But how long a time period are we looking at? Based on the local rate of crossing-over, we can say how quickly LD ought to be broken by new recombinations, and that allows us to derive age estimates. The ages represent the time that has elapsed since the initial mutation that established each adaptive allele.

Here is a comparison between the ages of selected variants in the African HapMap and in the European HapMap. Let's look at this graph a little bit.

Each of these dots represents a number of different genes -- the y-axis is number; this is a histogram. The x-axis is the age. So you see, there are many of these selected genes that started around 10,000 years ago; there are many fewer that started around 40,000 years ago, and even fewer starting 80,000 years ago.

These fitted lines are what you get if you fit a one-parameter model with very strong selection to these curves. You can fit these without considering the effects of population growth.

But you notice some differences here between the African and European distributions. Africa has a few more total variants, but it especially has more older variants, before 10,000 years ago. You can see that during that time period, Europe has very few. And Europe has this later peak, where we see an earlier peak in Africa.

These details are a very good match to demographic growth -- Africa had much larger population size during the Late Pleistocene than Europe, but West Asia, and then Europe had earlier Neolithic expansion than Africa -- so we see these early times have a lot more selected variants within Africa, and later on there is a pulse of adaptive variants in Europe.

Testing acceleration

At this point, we have a theory that predicts acceleration of new adaptive variants, and we have data that appear to show a very fast recent rate. But we haven't yet directly tested the hypothesis of acceleration.

We chose a null hypothesis approach. After all, the rate of change looks like it has been very high recently, but what it if were always very high. A constant rate of change is a null hypothesis -- the hypothesis of no change, or in our case, no acceleration. So we worked out the predictions of this hypothesis: a constant, high rate of selection. If we could show that those predictions aren't true, then we could disprove the null hypothesis and show that adaptive human evolution accelerated.

We took several different approaches, testing predictions on different kinds of data. For one thing, if the null hypothesis were true, then there should be a whole lot more selected mutations that have already reached or approached fixation, than the relatively small number that we see still varying in human populations. So to test the null hypothesis, we should look for evidence of these fixed selected substitutions.

That's exactly what we did -- we looked at other means of assessing the number of recently fixed and near-fixed variants.

On the bottom of this graph, we have the European age distribution of variants in our window. This should represent a small fraction of the total number that have happened across this time period. But you can see from this graph, that if the rate was constant, the total number should be very, very large -- since we are looking at 10-generation bins, here we have around 150 predicted substitutions every 10 generations, or around 1/2 per year. Most of these should be way above our window, in fact, as we go back toward 40,000 years ago, almost all should be close to or at fixation.

This large number of completed sweeps should have vastly reduced human genetic variation, because polymorphisms tend to hitchhike along with nearby selected alleles. Hitchhiking up to fixation tends to eliminate variation. When we look at the effect of hitchhiking under this constant selection hypothesis, the genome-wide average diversity should be less than a tenth of what we actually observe. So that also disproves the null hypothesis.

How much acceleration?

Down at the bottom of the graph, you see the predicted number of selected variants over our window, under the hypothesis of population growth -- exactly the demographic growth that really happened to humans. And here you see, that there are many, many fewer of these predicted, and in fact over the long course of human evolution, the rate would have been very low.

We can put a number on just how low, and when we do that, we can see how much human evolution has sped up. For example, if we have 1/2 of a substitution per year, well, there are around 12,000,000 years separating humans and chimpanzees (6 million since the common ancestor, in both these lineages). So if adaptive substitutions had happened at a constant rate as high as the last few thousand years, we should be looking at around 6 million fixed adaptive substitutions between humans and chimpanzees.

But in reality there have been nowhere near that number. There are only 40,000 total amino acid substitutions between humans and chimps. Not all those were selected -- maybe only a third. We can add in some additional selected sites outside of coding regions, but still we are looking at an increase in the rate of new adaptive mutations in humans that is 100 times faster than could possibly have been true during most of human evolution.

Our evolution has recently accelerated by around 100-fold. And that's exactly what we would expect from the enormous growth of our population.

What is all this selection for?

We know something about the functional categories of genes inferred to be under selection; we are studying this now. We expect it will keep us busy for some time.

In a general view, they illustrate the idea that changing cultures and ecologies have been important in changing the pattern of selection. For example, many of the selected genes are involved with pathogen defense -- for new pathogens that didn't always exist. Some are apparently related to metabolism or even directly to diet, in terms of processing new food sources. Of course, lactase is an excellent example in this category.

These are not the kinds of phenotypes that have a lot of visibility in skeletal remains. But we have a skeletal record of these populations during the last 40,000 years. We know a lot about what they looked like and how they changed. So we may try to relate the pattern of genetic, skeletal, archaeological, and other kinds of changes over time.

One obvious way to test hypotheses about these changes would be to sample ancient DNA from skeletons. In this way, we could see if the new selected alleles are in them or not. This spring, a paper by Burger and colleagues (PNAS) sampled ancient European skeletons, Neolithic skeletons, for the lactase persistence allele. They didn't find any who had that allele -- not a single one, and this is in Neolithic populations where today the allele is up over 90 percent in frequency. What is going on there?

In this case, it is quite obvious by considering population genetics. We have a very good date for this lactase persistence allele, from many sources -- it is around 6000-10,000 years old. And you can see in the figure, a new selected allele will remain at a very low frequency for a long, long time after its origin. Here, these skeletons were sampled at a time when the selection pressure favoring the allele was present, but the allele had not yet increased to a substantial frequency. In fact, this allele would have been rapidly increasing through these intermediate frequencies much more recently -- we're talking here about Roman times. And today it is over 90 percent in Scandinavia, but considerably lower in Italy and Southern Europe.

In the future, we will be able to sample for genes more widely in ancient skeletons. At the same time, we will be able to sample skeletal changes to try to correlate them with allele origins. That is some research that I have applied for a number grants to support, and I think it will be very promising.

Conclusion

I hope that this essay gives an introduction to the work we have done. This was based on a presentation about the research I gave earlier this year. There are many missing ends, and I'll be adding more information over the next several days about ways of testing for selection, as well as some of the more surprising implications of our research. I've written it without a bibliography, which I can direct you to the paper for a full set of references.

Amy Harmon explains some dog genetics in the NY Times today, in an article focused on whippets. The problem is that undesirable characteristics of some breeds are homozygote recessives for alleles that the breeders have been strongly selecting:

FORT MOTT STATE PARK, N.J. — When mutant, muscle-bound puppies started showing up in litters of champion racing whippets, the breeders of the normally sleek dogs invited scientists to take DNA samples at race meets here and across the country. They hoped to find a genetic cause for the condition and a way to purge it from the breed.

It worked. "Bully whippets," as the heavyset dogs are known, turn out to have a genetic mutation that enhances muscle development. And breeders may not want to eliminate the "bully" gene after all. The scientists found that the same mutation that pumps up some whippets makes others among the fastest dogs on the track.

They're going to apply genetic screening to eliminate the "bully" whippets, although the article doesn't explain just how. I suppose, they will use DNA screening results to decide to breed only heterozygotes with homozygote dominants, yielding a 50-50 chance of fast-running heterozygote offspring. But it seems to me, the breeders are just as likely to mate a bully with a slow homozygote dominant, getting 100 percent heterozygotes as a result.

It's like hybrid corn, except with dogs!

In fact, if they could make purebred lines for three or four alleles at a time, they would really vastly improve their ability to breed for fast dogs by hybridizing.

It's interesting how people find it much more disturbing to have a categorical difference between to individuals (like an allele) instead of a continuous difference. I mean, speed is a continuous variable, and we all know that different people vary in how fast they can run. This has been an unremarkable fact since the beginning of time. But somehow when genes get involved, people get all funny about it:

"It would be extremely interesting to do tests on the track finalists at the Olympics," said Elaine Ostrander, the scientist at the National Institutes of Health who discovered that the fastest whippets had a single defective copy of the myostatin gene, while "bullies" had two.

"But we wouldn't know what to do with the information," Ms. Ostrander said. "Are we going to segregate the athletes who have the mutation to run separately?" For the moment, it is whippet owners who find themselves on the edge of that particular bioethical frontier.

It was not exactly news to breeders that speed is an inherited trait: whippets were developed in the late 1800s specifically for racing. But knowing that one of her dogs was sired by a carrier of the gene, said Jen Jensen, a whippet owner in Fair Oaks, Calif., makes its championships seem "less earned." Ms. Jensen's suggestion that a DNA test be required for all dogs and that the fastest ones without the mutation be judged and raced separately, however, has not gone over well.

I suppose the disquieting part is that genetics somehow reduces everything to simple mathematics. Keeping two strains of loser dogs for crossbreeding really fast ones will take away from the stuff about "spirit" and "magic":

Even those who want to exert more direct control over dog DNA, however, agree that no genetic test can predict the intangible qualities that make a dog great.

If a dog does not have the spirit to run a race, it is not going to win, said Betsy Browder, a whippet owner in College Station, Tex.

"'Keenness' is what we call it," she said. "Just like you can have a human athlete who's really lazy, and all the genes in the world aren't going to help."

Yeah, until they find the gene for that, too.

This stuff about separating out the human athletes by genotype is nonsense. There will always be this problem -- is it an athlete's training or gene X? Or as-yet-unknown-effect gene Y? Or gene Z in combination with her genetic background? Is it fair? I suppose that depends on the other consequences of genes X, Y and Z, and the entire genetic background. Which is the same question as, "Is life fair?"

At the moment, training discrepancies are quite a bit greater than most (though not all) genetic differences between athletes. But that won't remain true forever -- eventually, all credible competitors will have the same training -- or at least training that they believe to be the same. The training may even be specialized for their genotype. All they're doing is substituting one kind of variance (environmental) for another (genetic).

The only thing fairer is flipping a coin at the start of each race. Maybe some of them will want to trade, but I doubt it.

Planting time has arrived in most of the country -- even here in zone 4 -- so you may be reading those seed packets carefully. This paragraph may catch your attention:

One anti-biotech group even managed to bamboozle some seed companies that cater to home gardeners into signing on to something called the Safe Seed Pledge: "We pledge that we do not knowingly buy or sell genetically engineered seeds or plants." This is fascinating because, with the sole exception of wild berries and wild mushrooms, all the fruits, vegetables and grains in North American and European diets have been genetically modified or engineered by one technique or another. This even includes 'heirloom' varieties of fruits and vegetables. Often, this genetic modification has involved radical changes at the level of DNA, including the movement of genes or even entire chromosomes across natural breeding barriers.

That's from a TCS Daily column by biotechnology analyst Henry Miller. This is a point that constantly amazes me -- do people not realize that it is unnatural to have purple potatoes and zebra-striped tomatoes, and all other manner of garden mutants? That, for the most part, it is unnatural for vegetables (i.e., non-fruit and non-seed plant parts) to be tasty and delicious? Plants don't want you to eat them!

Most of the column is devoted to reviewing some of the misleading parts of a recent report on international biotechnology trends by the Organization for Economic Cooperation and Development. It's a fair critique, but a little dry for light reading. Certainly it's valuable to have critics go through definitions in these international reports, because so much of the conclusions are essentially determined by the assumptions that go into compiling lists. Some countries look different than others, just because their regulatory agencies define things in different ways.

I approach this issue from the perspective of teaching the debate in my genetics course, and also as a way to examine how the debate around human genetic engineering may be framed in the future. After all, franken-people are bound to be a lot more interesting than franken-food.

Not to mention the possibility of Neander-people -- or, dare I suggest, NEANDER-FOOD!

I find the trend toward GMO production of pharmaceuticals to be a very interesting angle in the current biotechnology scene, because of the clear resonance of the issues with human genetic alteration. Both the opposition and promotion of GMOs have both involved heterogeneous groups of interests. Much of the muscle behind both positions has come from agriculture industry groups -- So far, the critics of GMO deployment have been successful when they frame their opposition in terms of risk of introgression into non-GMO crops or wild plants. They have also had success with the "natural food" frame.

A month or so ago, I referred to an article that discussed the potential of introgression by plants genetically engineered to produce pharmaceutical compounds. Quoted in the article, Norman Ellstrand asked, why not modify non-food plants, and thereby eliminate all risk of consumption?

In his article, Miller gives an answer to this question:

Although there is substantial and growing acreage of gene-spliced crops cultivated worldwide each year - 252 million acres in 2006 - more than 90 per cent of it is four large-scale commodity crops; largely because of the huge costs of meeting regulatory requirements, the application of the technology to fruits, vegetables and subsistence crops has been minimal, and disappointing.

In short, it is easier to get approval for altering one of the four major food crops, because they have a research history and are already grown on a immensely large scale. Introducing genetic modification on another kind of plant requires much more work to conform to regulations.

There is also the issue of a less-recognized mode of genetic modification; namely, Simpsons-style:

Currently, dozens of genetically improved varieties that are produced through hybridization, irradiation and other traditional methods of genetic improvement enter the marketplace and food supply each year without any governmental review or special labeling. A technique in use since the 1950s, induced-mutation breeding, involves exposing crop plants to ionizing radiation or toxic chemicals to induce random genetic mutations. These treatments most often kill the plants (or seeds) or cause detrimental genetic changes, but on rare occasions the result is a desirable mutation. For example, a mutation might produce a new trait in the plant that is agronomically useful, such as altered height, more seeds, larger fruit or enhanced resistance to pests.

On a large scale, these random mutations pose more potential of introgressing into wild plants, because they don't carry the baggage of a plasmid, and they might have unknown beneficial side effects on plant fitness. Plus, a strain bearing many random mutations might have some unintended ones along with the one that is strongly selected by subsequent breeding. This kind of induced-mutation breeding is really nothing more than ordinary breeding sped-up a little faster, but then, the only thing making trans-species gene transfer different is that you know in advance that the inserted gene works in some other organism.

In a previous column, Miller argued against legislation being considered to regulate the farming of gene-spliced plants in California. At the same time, he points out the harmful consequences that sometimes result from conventional breeding:

This measure is pointless. In the production of new plant varieties using conventional - that is, pre-gene-splicing - techniques, breeders, farmers and food producers lack knowledge of the exact genetic changes that produced the useful traits. More important, they have no idea what other changes have occurred concomitantly in the plant -- including those that could alter the ability to cause allergic reactions.

...

Only the molecular, gene-splicing methods allow breeders to identify and fully describe the changes that have been made in the progeny, so perhaps it isn't surprising that only the imprecise, trial-and-error techniques of conventional plant-breeding methods have led to food safety problems. Two conventionally bred varieties each of squash and potato and one of celery were found to contain dangerous levels of endogenous toxins and had to be barred from commercialization. Such mishaps are far less likely when genetic changes are wrought with the more precise and predictable gene-splicing techniques.

The difference is not mainly that the trans-species genes are predictable in effect, but that they are introduced only a few at a time. This is less likely to cause incidental side effects than altering the frequencies of many genes by conventional breeding. The point is that anything that we change may generate bad side effects, and we want to find ways to minimize these. One approach is not to change anything. But since nature changes things for us anyway, maybe best to change with science...

R. Ford Denison's blog, "This Week in Evolution," has become a very interesting read since he began a couple of months ago. Denison recently attended a symposium titled, "Darwinian Agriculture: the evolutionary ecology of agricultural symbiosis." He summarizes the basic idea of "Darwinian agriculture" in his pre-meeting post:

"Darwinian Agriculture: when can humans find solutions beyond the reach of natural selection?" was the title of a paper that Toby Kiers, Stuart West, and I published in 2003. Our answers to the title question suggested how increased understanding of past and ongoing evolution could improve: 1) breeding of crops and livestock, and 2) design of agricultural ecosystems.

With respect to genetic improvement of crop plants, we wrote:

"most simple, tradeoff-free options to increase competitiveness (e.g., increased gene expression, or minor modifications of existing plant genes) have already been tested by natural selection. Further genetic improvement of crop yield potential over the next decade will mainly involve tradeoffs, either between fitness in past versus present environments, or between individual competitiveness and the collective performance of plant communities."

Since then, every time I give a talk on this subject, I look for papers that might disprove this tradeoff hypothesis. I also look for examples of tradeoffs that were rejected by natural selection, but which might be acceptable in agriculture. For example, many people are working on improving drought tolerance of crops. Is it possible to improve on natural selection for this trait?

In other words, the concept is something like the agricultural version of evolutionary medicine. The past is important to the present, and understanding how crop plants were selected in past environments (both natural and agricultural) helps us to predict the likely constraints on their current adaptive potential. Further, those constraints might be relaxed by trading off some traits that in the past may have been strongly selected, but at present are of less adaptive importance.

Few people working to unravel evolutionary history stop to think about the practical implications of this research. And unfortunately, few people working in applied fields like agriculture or medicine think much about how knowledge about evolutionary history can be applied to modern problems. But this is changing -- more and more, it has become clear not only that the present is a product of the past, but also that the past helps to determine the future.

A second post was a follow-up to the symposium, reviewing some of the papers presented. A couple of papers on genetic diversity in modern cattle and their relationships to European aurochsen are reviewed. These are very interesting, and of course Greg Cochran and I wrote a short review of this story in our introgression paper last year.

Denison's quick review of his own presentation is a good illustration of conflicting selection in crop evolution, and attempts to reduce counterselection:

Finally, I talked about breeding crops that yield more per acre (or hectare) because individual plants compete less with each other. The best-known example is plant height. Short plants make more grain because they waste less on stems. This works well if you have a whole field of short plants. But, in a mixture, the taller, low-yield plants shade out the shorter high-yield plants. Plants that branch less can yield more, in monoculture, but can't compete against plants that branch more.

In this way, the unique practices that have helped to make agriculture such a productive system for humans can actually impede further response to selection -- as genetic variation within crop plants can include strategies that defy attempts to select for a given trait. It's game theory applied to corn! More to the point, selecting for short plants is an inefficient way to deal with the problem. Hybrids (and cloning) work as farming techniques not only because of overdominance, but also because making sure that your entire field is genetically uniform is a way of reducing the strategy options available to the plants.

One of the papers also covered the ecology of a non-human agricultural analogue: ant fungus farming:

In ant gardens, contact between two different fungal strains triggers a negative reaction that reduces growth. Even manure from ants that ate one strain will trigger this reaction in a second strain. In termite gardens, different fungal strains don't fight. But they don't bond, either, and this also limits growth. Over tens of millions of years, ants and termites have evolved behaviors that maintain their gardens as fungal monocultures. Ants remove alien fungi, even strains that might be grown by another ant colony. Termites prevent their fungi from reproducing sexually, by eating fruiting bodies that could produce sexual spores. Without sex, one strain gradually takes over.

Now that's what you call selective breeding. Of course, they have the same aim as humans. The best way to maximize the energy return of the fungus is to eliminate the possibility that it can disperse without your help! If you don't want your domesticate to lose productivity to cheater strategies (which attempt to disperse on their own), then you had better cut off all possibility of gene flow into your fungus garden.

Denison points out at the end of his post that this farming strategy itself is not always optimal:

Whether we look at ant or termite fungus gardens, microbes that help crops, or crops themselves, diversity can lead to interactions that reduce growth. Should we work to reduce diversity in agriculture, then? Not exactly. Diversity may be useful at some scales, but harmful at others. If the world grew more different crops, a disease that killed any one crop would have less effect. But that may not mean that every field should contain more than one crop.

Some of this confirms common sense -- Denison mentions crop rotation as a long-employed diversity management technique. But the details of the interactions of plant ecology, human management practices, and genetic correlations among different traits will be central to the future of agricultural science. It's a clear example of the practical importance of evolutionary theory.

Related posts here:

Roundup ready, a review of glyphosate resistance linking to a story on the emergence of coca plants resistant to Drug War-related herbicides.

More on bison and introgression, a post covering attempts to breed cattle genes out of bison, and vice versa.

The inevitability of introgression, covers my paper with Cochran.

Breeding nutritional Neanderwheat, on the introduction of genes from wild wheat relatives into domesticated wheat.

This is a nice little article in the times by "collaborative problem solving" director Denise Caruso

A NEW generation of genetically engineered crops that produce drugs and chemicals is fast approaching the market -- bringing with it a new wave of concerns about the safety of the global food and feed supply.

The plants produce medicinal substances like insulin, anticoagulants and blood substitutes. They produce vaccine proteins for diseases like cholera, as well as antibodies against tooth decay and non-Hodgkin's lymphoma. Enzymes and other chemicals from the plants can be used for a range of industrial processes.

As in past debates over genetically modified crops, biotech developers say that the benefits outweigh the risks, and that the risks are manageable. Critics question the benefits, and say the risk of a contaminated and potentially toxic food supply is untenable.

Ellstrand was a good expert to interview -- I included several of his articles in my introgression bibliography -- and his points seem like the most relevant ones:

"I don't think that engineering plants for pharma is a bad idea, with two caveats," Professor Ellstrand said. One, he says he thinks that planting should be done in greenhouses rather than in open fields. "The other issue is food," he said. "Why do we have to do this in food crops? It doesn't matter what you're squeezing the compound out of. It could be a carnation, a corn plant or a castor bean."

That last seems like a good point: why not switchgrass or something? I suppose that the real answer to this question is that there is lots of farm equipment that is designed to deal with the seeds of existing agricultural crops, making the economics of these plants much more appealing than non-food plants. But there probably is some compromise crop that would suit this concern.

Maybe they could find a way to make drugs in plants destined for ethanol -- two birds with one stone.

Either this continues today's Kansas theme, or this week's genetics theme. In either case, it's nice to see some attention to agricultural genetics and its growing connection to energy economics, in this Times article:

Like his father and grandfather before him, Mr. Kepley grows wheat. But energy costs that have quadrupled in three years, along with one of the worst droughts to grip the region in a century, have made it too expensive for him to irrigate. So today Mr. Kepley grows wheat under dry-land conditions, capturing rainfall for two years to make one year's crop.

"These are called semi-dwarfs," he said while surveying his burnt-looking wheat stalks one recent afternoon. “Our geneticist started developing this. Generally our wheat will be about knee-high when it is harvested. It doesn’t use much energy in developing the stalks.”

The theme is that pumping water has become more and more expensive with increasing energy costs, and farmers are looking for improved draught-tolerant breeds to help compensate. It's not a cure, since productivity and diversification both are improved with irrigation, but it can be a more economical solution as irrigation becomes more expensive.

Genetically engineered creeping bentgrass has been found growing miles from a test plot where it was planted two years ago, according to a NY Times story:

Two years ago, scientists at the E.P.A. laboratory in Corvallis, Ore., published a paper showing that pollen from a test plot of the grass had spread as far as 13 miles downwind, much farther than many had expected. That made it likely that genetically engineered grass would be found in the wild, though the scientists did not look for that.

In the new study, scientists sampled 20,400 plants up to three miles from the edge of an 11,000-acre zone surrounding the test plots. They found 9, or 0.04 percent, that were genetically engineered, the farthest being 2.4 miles from the control zone border.

The scientists said some of the plants had been created by seeds that had blown off the test plot and others by hybridization of wild grass with pollen from the genetically engineered grass. All were of the same species of grass being developed by Scotts and Monsanto.

I generally think genetic engineering of crops is a good idea, although I would prefer it not be used in the service of easier monoculture -- which these golf course grasses certainly are.

But articles like this always miss the point about the escape of plants or genes into wild populations. They tend to make it sound like the rate of escape is the limiting factor -- as if a low or "negligible" rate of escape will prevent gene flow to wild populations.

However, in reality it is the advantage or disadvantage an an introduced allele that determines whether it will spread or not. Wild populations are pretty well adapted, so in almost all cases an introduced allele (or gene) is likely to fail. But once in a while they may succeed -- especially if the gene is very different from alleles that might have arisen naturally (like moving genes from rice to corn), and if the trait is related to biotic resistance or drought tolerance or other ecological problems shared with wild plants.

And if an escaping gene begins with a few copies, it will take a long time to reach an appreciable frequency in the wild. In other words, the effects are long-delayed.

Unhappily, natural selection has no test plots for us to figure out in advance which genes will be adaptive in wild populations, and logic only takes us so far. So we're left with uncertain consequences, that may take a long time to manifest themselves.

I think in most cases, the risks of transgenic organisms are pretty minor compared to their economic benefits (which include feeding people who would otherwise be hungry). But it would be nice if other -- nonpatentable -- approaches to increasing production were getting some of the resources going into trangenic organisms.

On the topic of biotechnology, this AP article describes Ventria Bioscience's field tests of rice altered with a human gene:

Ventria, with 16 employees, practices "biopharming," the most contentious segment of agricultural biotechnology because its adherents essentially operate open-air drug factories by splicing human genes into crops to produce proteins that can be turned into medicines.

Ventria's rice produces two human proteins found in mother's milk, saliva and tears, which help people hydrate and lessen the severity and duration of diarrhea attacks, a top killer of children in developing countries.

Critics say that the practice of farming these genetically modified plants in the open air may "contaminate" conventional crops; the company argues that rice is self-pollinating and the spread of the gene is virtually impossible.

The potential payoff is interesting. The idea is that the protein, expressed in human breast milk and saliva, will help to fight diarrhea, particularly in infants and children. From a PR standpoint, of course that brings in the concept of helping children in developing countries, which has been such an effective argument in favor of the so-called "golden" rice enriched with vitamin A.

But from the article it appears that the company has a bigger market in mind:

Ventria hopes to add its protein powder to existing infant products. There is no requirement to label any food products in the United States as containing genetically engineered ingredients.

The company also has ambitious plans to add its product to infant formula, a $10 billion-a-year market, even though the major food manufacturers have so far shown little interest in using genetically engineered ingredients. But Deeter says Ventria can win over the manufacturers and consumers by showing the company's products are beneficial.

"For children who are weaning, for instance, these two proteins have enormous potential to help their development," Deeter said. "Breast-fed babies are healthier and these two proteins are a big reason why."

I think parents will buy it, and it might well be an improvement on regular infant formula -- which lately has been getting various kinds of protein additives to make it "more similar" to breast milk.

Now, I hadn't considered this:

How would the world feel, how do you feel, knowing that at the moment you are reading this you may be wearing transgenic underpants?

Happily, the New York Times has me covered. No, not that way!

Yes, it's that kind of story.

Despite some opposition to genetically modified crops, even ones not grown for food, Frankencotton has been so successful that it is now grown all over the world, including the United States. It is particularly popular in Asia.

According to a recent report in The Proceedings of the National Academy of Sciences by researchers at the University of Arizona, farmers who grew Bt cotton reduced their use of pesticides and increased the diversity of their insect populations, while protecting crops against the dread pink bollworm.

A similar genetic modification in corn has caused an uproar. Many countries have rules about labeling food that contains genetically modified organisms, or G.M.O. Zambia, for instance, has refused to import transgenic corn. But cotton has faced no such trade barriers.

The obvious reason is that people tend not to eat their shirts.

Paul Elias of the AP reports on how geneticists are trying to make tastier hogs:

Even before the pig genome is completed sometime next year, top commercial producers such as Pig Improvement Co. and Monsanto Inc. are using preliminary results from genetic screens to see if they can determine which pigs are the tastiest before they are butchered. The screens will also be used to manage herds and make breeding decisions, among other improvements.

"They can now look inside the pig," Rothschild said. "They are both building better pigs with this technology."

Cattle, too:

Minnesota-based Cargill Inc., which supplies about 20 percent of the nation's beef, is working on a genetic screen to sort its cattle by the quality of their meat, something that can't be done now until the animal is slaughtered.

Cargill is testing the screen on 30,000 of its cattle. If it works, the company can reserve the best feed and care for its prime beef producers, or ensure that the best animals mate with each other.

The idea is that you eliminate a lot of guesswork by having direct genetic assays for alleles that correlate with meat quality -- instead of selecting indirectly through the observed qualities of genetic relatives.

Most people aren't aware of how much math goes into breeding science -- and this article isn't all that helpful, calling it an "art". It's probability theory, not an art!

In any event, genotyping is a way to raise certain probabilities, and in so doing cuts out a lot of math. It's just ironic that it takes computer screening to help us make meat taste better!