My dogs' evolutionary history. Part 2: Results

Yesterday we made the predictions of the breed signatures we'd find in our dogs' DNA.

If you didn't already, please consider going back to yesterday's post first before reading today's. Predictions are key! It's best if you confirm our guesses and/or add your own. (...what are the reasons for your predictions? Size? Color? Ears? Tails? Fur? Snout? Furnishings?)

Sadly (yes, sadly), predictions are not part of the official Wisdom Panel or 23andMe experiences. When I teach with 23andMe predicting the results is a major assignment early in the semester. Not only is making predictions the best practice for later scientific evaluation of the results, and it's the best way to force yourself to come to terms with how inheritance and gene expression work (and don't work), but guessing the outcome first makes reading the results orders of magnitude more fun ... not to mention how it makes things a lot less nerve-wracking when it's about your own DNA with 23andMe.

Briefly, before I reveal our dogs' results, let's consider a couple important things first...

Dog breed markers are mutations. 
Just like anything else alive right now, all dog breeds, no matter how "pure" or revered, are mutants. All of their dog traits just like all of our human traits, good and bad, started out as new mutations. Even the ones we all share that contain little variation now (like our genes involved in the development of five fingers and five toes), but also the ones that vary among our populations (like our genes that affect our pigmentation).

And mutations aren't just a population thing; each of us has a tiny fraction of our genome that's mutated compared to our parents. As far as we know, mutations occur in the making of all babies and puppies, etc. Most are neutral, some are bad, some are good.

We're all mutants because mutation, perpetual change generation upon generation within a lineage, is constant. Stasis is not.

This constant change in every puppy is fundamental to why we can have hundreds of dog breeds today.

Many dog breed traits are genetically simple.
Dogs seem to be particularly simple kinds of mutants.

The mutated genes that determine the traits that distinguish one dog breed from another are remarkably few and remarkably simple, but that simplicity makes a lot of sense.

Since humans coaxed these breeds out of ancestral dog stocks and also out of other breeds (as they still do today), it's easy to imagine that new simple traits, not new complex ones, had the best potential to be easily and quickly propagated into future generations and eventually into new breeds.

If a trait arose that was preferred, and it was caused by the kind of genetic mutation that could be simply and somewhat reliably expressed in offspring that inherited it, that mutation and the trait it produced could be increased in future generations by promoting breeding of those new attractive mutant dogs and their offspring.

(source)

If dog breed traits were genetically complex (based on many genes, for example), they would be terribly difficult to produce through controlled breeding of parents with those traits... at all... let alone during one human breeder's lifetime! That's at least partly because there would be far too many puppies without the preferred trait and it would be far too difficult to preserve a trait at an appreciable frequency in a lineage. Of course, inbreeding with very close relatives that share the mutations helps a great deal with this.

Humans have taken advantage of the simple mutations that have popped up in dogs (as they pop up in all living things!), due to sheer feasibility of the breeding outcomes those simple mutations allowed. Like that new coat curl or those new furnishings? Some puppies will have the exact same look. And we're off and running with a new kind of dog...

(source)

I don't know about the genes for Dalmatian spots (and honestly haven't even looked) but I do know about this paper by Cadieu and colleagues from 2009. Apparently you need only three genes (FGF5, RSPO2 and KRT71), each with two alleles (i.e. gene variants; denoted +/- in the figure below) to explain all this coat variation among dogs:

Cadieu et al., 2009

Dog genes are made of the same goop that ours are, and their genomes are very similar to ours because of our shared mammalian ancestry, but they're described as "simple." Evan Ratliff explains some more about why dog genes are simple in "How to Build a Dog:"

The vast mosaic of dog shapes, colors, and sizes is decided largely by changes in a mere handful of gene regions. The difference between the dachshund's diminutive body and the Rottweiler's massive one hangs on the sequence of a single gene. The disparity between the dachshund's stumpy legs—known officially as disproportionate dwarfism, or chondrodysplasia—and a greyhound's sleek ones is determined by another one. The same holds true across every breed and almost every physical trait. In a project called CanMap, a collaboration among Cornell University, UCLA, and the National Institutes of Health, researchers gathered DNA from more than 900 dogs representing 80 breeds, as well as from wild canids such as gray wolves and coyotes. They found that body size, hair length, fur type, nose shape, ear positioning, coat color, and the other traits that together define a breed's appearance are controlled by somewhere in the neighborhood of 50 genetic switches. The difference between floppy and erect ears is determined by a single gene region in canine chromosome 10, or CFA10. The wrinkled skin of a Chinese shar-pei traces to another region, called HAS2. The patch of ridged fur on Rhodesian ridgebacks? That's from a change in CFA18. Flip a few switches, and your dachshund becomes a Doberman, at least in appearance. Flip again, and your Doberman is a Dalmatian. "The story that is emerging," says Robert Wayne, a biologist at UCLA, "is that the diversity in domestic dogs derives from a small genetic tool kit."

So it's this simplicity that allows companies like Wisdom Panel to genetically distinguish breeds and then look for the signatures/markers of those breeds in our dogs' DNA. It's also the recency of most of these breeds (no more than a few to several hundred years at most) that allows us to assume (maybe not rightly but still...) that so much of what genetically identifies a breed today is similar to what the breed was working with all along.

And so... without further ado...

Here are the results of mailing off our dogs' cheek swabs and having 321 markers for 200 breeds analyzed.

For Elroy...
This is his "Breed Ancestry Certificate"

The report notes how Rottweiler and Chow Chow are the only ones with confidence. 

How do they make the pedigree chart? 

What I think they do is estimate what percent of the breed contributes to the dog's ancestry and if it's something like 50%, it's one parent. If it's like 25%, it's one grand-parent and if it's like 12.5%, it's one great-grandparent. Any % less than that is lumped into "mixed breed" ... the details of those are guessed at below.  So those placements on either side of his chart are just best fit in terms of percentage. 

What I'm not sure about is why we must assume that 100% of Elroy's ancestry comes from any breed. But, remember that 100% of the markers in the Wisdom Panel test distinguish breeds. That means, this Breed Ancestry Certificate is missing all the information about Elroy that's not analyzed by Wisdom Panel. 

Non-surprises.
We guessed the breeds that they were confident about! There must be something to this test. Especially since we had seen his litter mates and were told by the adoption agency that he was probably rott/sharpei (and later on we figured he was just as likely chow chow as sharpei). SCIENCE works.

Surprises.
German Shepherd and Collie aren't terribly surprising either. He came from Ohio. Those breeds are abundant enough in the region, are allowed to roam free and probably mated like that too for decades upon decades in those regions. And he's a big boy!

But Westie? Westie is a bit of a head-cocker.

Or is it? Westies had to have had big ancestors, first of all, since they descended from wolf ancestors like all other dogs. But something that distinguishes Westies from other breeds is in Elroy's DNA. That means a relatively recent Westie left a signature in his genome. So was it kamasutra lovemaking between tiny Elroy ancestor and big Elroy ancestor?  Or are we talking about love between mixed breeds and pure breeds and mixed breeds over time? Probably.

Here are their best guesses about what contributed to those "mixed breed" mysteries on his certificate.

Mostly big dogs, some ancient and awesome. The Dogo! (Ugh, don't google it... so many fighting and abuse videos.)

Nothing to really take home from this list because they're far off guesses without even a report of percentage there with the bar graph.

For Murphy...
This is her "breed ancestry certificate"

Akita, German Shepherd and Lab are the only confident ones (as noted in the report). 

And here are the most likely breeds contributing to those "mixed breed" mysteries on her certificate.

Non-surprises.

Shepherd! And Lab is another good one considering friends and relatives see lab in her.
Many of her mix guesses are herders!

Surprises.
Akita? That's phenotypically (and maybe genetically(?) will have to check) close to Husky which is another guess we often hear for her. So this is only a little bit surprising.

French Bulldog? Now that's a real head-cocker.

But again, like with the Westie, it's not noted as "confident" in the report, but on the other hand, why not French Bulldog in her ancestry? It just means this is a marker, like with the Westie, that's not tied to outward appearance/phenotype.*

Not enough information...
I wonder what these markers are then; if Westie and French Bulldog are showing up, why? As the website explains, “Physical features characteristic of certain breeds, such as the flattened face of the English Bulldog or the extremely curled tail of the Pug, seldom survive even the first crossbreeding.”

So these markers for unseen traits are fascinating but not explained in the report.  I'm spoiled rotten by 23andMe that tells you everything, down to the A,T,C, or G you have for your allele for whatever gene. I'm guessing that Wisdom Panel keeps all this under wraps because (a) most consumers don't care to know those details and (b) it's in their best competitive and economic interests to keep their methods to themselves.

What's interesting is how some of the hype about these dog tests is similar to 23andMe: They're "for your health!" But unlike with 23andMe, Wisdom Panel says that you're good just going to your vet and saying "she's got Akita in her blood" when you're dealing with health issues.  While 23andMe advocates that you know each and every SNP.  My health is more important than my dog's I suppose, but what's absolutely not clear is how these two very different approaches (ancestry and family history vs. SNP data) are resulting in different health outcomes.

As you might imagine, there's a lot more to say about the evolutionary and anthropological issues these dog tests raise, so please stay tuned. (Here's part 3.)

Kevin and me and our Westie, Elroy, and our French Bulldog, Murphy.

*Or if it is, it's present in only one recessive copy and would require two copies for the visible trait in the Westie or French Bulldog  to be expressed (added June 14)

My dogs' evolutionary history. Part 1: Predictions

[Click here to skip to Part 2 and Part 3]

You might remember Murphy and Elroy from the time we used science to solve the book-eating mystery. Or the time they figured out evolution. (Still looking for puplisher! [sick]) Or maybe you already know Elroy because you follow him (@ElroyBeefstu) on Twitter.

Elroy (I fit in your phone!)

Murphy (awww)

These are the mutts that inhabit our lives, and we theirs.

It's because of our tremendous love for these dogs but mostly because of our tremendous fascination with evolution that we ordered Wisdom Panel kits for each, for my birthday.

What we do

With Wisdom Panel, the process on the consumer end isn't a whole lot different from 23andMe. You purchase the kits online, they arrive at your house, you activate the kits online, you swab your dogs' mouths, pop the kits back in the mail with the postage-prepaid packaging, and wait for an email with the results.

Wisdom panel needs far less of the contents of a dog's mouth than 23andMe requires. And that's not only because the analysis will be far less extensive, but because dogs' lips and face muscles aren't hooked up for spitting into a test tube.

The turnaround was speedy. We sent in the samples on May 28 and got the results June 6.

At this stage in the process, the only red flag is that they require you to submit your dog's weight during online registration. For the love of science, there should be no phenotypic hints required. I hope they don't use weight to discard or confirm dog breeds for their results report.

What they do
Here's what the FAQ says:

Testing your dog with Wisdom Panel® 2.0 begins when you use the cheek swabs to simply collect a small DNA sample from inside your dog’s cheek and send the swabs into the laboratory. Once your sample is received at our lab it is scanned into our database and assigned to a batch for testing. It then undergoes processing to extract the DNA from your dog’s cells which is examined for the 321 markers that are used in the test. The results for these markers are sent to a computer that evaluated them using a program designed to consider all of the pedigree trees that are possible in the last three generations. The trees considered include a simple pedigree with a single breed (a likely pure-bred dog), two different breeds at the parental level (a first-generation cross), all the way up to a complex tree with eight different great-grandparent breeds allowed. Our computer used information from our extensive breed database to fill these potential pedigrees. For each of the millions of combinations of ancestry trees built and considered, the computer gave each a score representing how well that selected combination of breeds matched to your dog’s data. The pedigree with the overall best score is the one which is selected and provided to you in your dog’s individualized report.

This doesn't really cut it for me. I want to know what the methods are and this is all they provide in answers to "Science Based Questions!" This isn't helping much:

Not only does the computer analyze a dog’s DNA for the breeds and their likely proportions in the dog’s ancestry, but it also models which side of a dog’s ancestry each breed is likely coming from.

I'll just have to assume for now that they use something like a chip (because sequencing is still not thrifty) to identify markers that they've already linked to breeds and then they're applying their probability-based analyses to those markers in our dogs in order to provide an estimate of our dogs' ancestry. And what are those markers?

Wisdom Panel only uses what are called autosomal DNA markers, chromosomes that contain most of the genetic instructions for every canine’s body make up (height, weight, size etc.). There are no markers from either the so-called sex chromosomes (the canine X or Y chromosomes). Mitochondrial DNA, or Y-chromosome DNA testing, is rather different as these parts of the genome are passed on intact from mother to child and father to son respectively, but are therefore only representative of either the female or the male lineage. Autosomal DNA is inherited both from the maternal and paternal lineages equally and constantly shuffled by a process called recombination at each successive generation, and therefore is able to give useful information on the breeds found on both sides of a dog’s lineage.
To find the genetic markers that performed best at distinguishing between breeds, Mars Veterinary™ tested over 4,600 SNPs (single nucleotide polymorphisms or genetic markers, where genetic variation has been found between different dogs), from positions across the whole canine autosomal genome from over 3,200 dogs. To further refine the search, Mars Veterinary determined the best 1,536 genetic variations and ran them against an additional 4,400 dogs from a wide range of breeds. This stage of testing resulted in the selection of the final panel of DNA markers that performed best at distinguishing between breeds, ultimately creating the Wisdom Panel genetic database which presently covers over 200 different breeds.

Predicting our results
Both Elroy and Murphy are mixed breed dogs. Here's the list of breeds they say they can detect.  And here's more from the website:

Wisdom Panel® 2.0 breaks down a dog’s lineage in the form of an ancestry tree.  This allows you to see which breeds are present at a parent, grandparent, or great-grandparent level.  Keep in mind that a parent contributes 50% of their DNA to the puppy while a grandparent contributes about 25% of their DNA on average to the puppy.  It follows that a great-grandparent would contribute approximately 12.5% of their DNA to the puppy on average.
Since each of these different levels can contribute different amount of DNA to the puppy, you can see a variety of influence in the puppy’s physical and behavioral traits.  With a parental breed, you are likely to see some physical and behavioral traits from this breed represented unless some of the genes are recessive (requires two copies of the gene variant to show it).  Examples of recessive traits include longhair in most breeds, a clear yellow or red hair coat, a brown or chocolate hair coat, and prick or upright ear set (e.g. like a German Shepherd Dog).  You may see traits from breeds at the grandparent level and it becomes less likely to see physical and behavioral traits from breeds at the great-grandparent level unless those traits are dominant (requires only one copy of the gene variant to show it).  Examples of dominant traits include shorthair in most breeds, black hair coat, black nose, a drop or down ear set (e.g. like a Beagle), and merle/dapple (e.g. like a Australian Shepherd or Great Dane).

For Elroy (85 lbs)
Our guesses = 50% sharpei or chow chow; 50% rottweiler

Kevin was told he was half sharpei and half rottweiler when he adopted him and all his litter mates were black and looked like rotts. He's got tiny ears and a huge square head and heavy neck relative to his body.

We started to wonder whether he was chow chow instead of sharpei when I checked my best dog reference for another breed with a black tongue.

If he's part chow chow then my envy of his fur is no longer so crazy, since the breed was long made for that... and for dinner too. It makes me chuckle every time I call Elroy's dinnertime, "chow time."

For Murphy (40 lbs)
My guess = 25 % German shepherd; 25 % Border collie; 25 % Hound of some kind; 25% unknown village dog. Kevin's guess = 25% German shepherd; 75% Border Collie

Before her greybeard took over.

Unlike for Elroy, Murphy's behavior came into play for these predictions. Her main occupation is to herd each car that comes down the lane along the edge of our lot. She also stalks squirrels and chases shorebirds. And compared to Elroy, she doesn't have as many breed-specific morphological traits.

Who knows? We could be way off. After all, I just took this Dog Bark Interactive Quiz and failed miserably despite knowing exactly what Elroy and Murphy's vocalizations mean.

Results and analysis, right here, tomorrow...

Mighty mites...or mighty misleading?

The April 11 broadcast of BBC 4's Material World included a discussion of the rapid evolution of mites.  A paper published online on April 8 in Ecology Letters described an experiment in which researchers at the University of Leeds brought soil mites into the lab, put them into 18 test tubes at high population densities, removed 40% of the adults from 6 tubes, 40% of the juveniles from a further 6 test tubes, and didn't harvest any from the remaining tubes.

As described by Futurity.org,

Researchers found significant genetically transmitted changes in laboratory populations of soil mites in just 15 generations, leading to a doubling of the age at which the mites reached adulthood and large changes in population size.

The results have important implications in areas such as disease and pest control, conservation and fisheries management because they demonstrate that evolution can be a game-changer even in the short-term.

Said a post-doctoral collaborator on the project, “The age of maturity of the mites in the tubes doubled over about 15 generations, because they were competing in a different way than they would in the wild. Removing the adults caused them to remain as juveniles even longer because the genetics were responding to the high chance that they were going to die as soon as they matured. When they did eventually mature, they were so enormous they could lay all of their eggs very quickly.”

"Our study proves that the evolution effect--
the change in the underlying biology in
response to the environment--can happen
 at the same time as the ecological
response.  Ecology and evolution are
intertwined," says Tim Benton.
(Credit: University of Leeds, via Futurity.org)

Now, the experiment and its results sound interesting.  If the investigators did their genetics right, they showed that a number of genes, 7 of which they said they'd identified, contribute to the life-history change.  So these results might provide worthwhile results in terms of understanding the control of metamorphosis or growth etc. in this species, and probably therefore beyond it.

However, in our view this story totally misrepresented what it had found, in a way that reflects the current mesmerization of science as well as the public, in terms of making huge unwarranted claims and invoking genetic determinism way beyond reason.  Why do we say this?

The author of the study who was interviewed seemed to claim, and the interviewer accepted without question, that his results cast doubt on the central Darwinian tenet that evolution is a very very slow, gradual process.  This is dramatically wrong in at least three respects.

First, this was not natural selection, imposed blindly by the natural ecology of any species, but instead was imposed intentionally from the outside in a way thoroughly controlled by the investigator and made very intense.  It is, in fact, artificial rather than natural selection. Darwin used artificial selection as his model for natural selection, claiming that the same process that farmers and dog or pigeon breeders used to achieve desired states was what occurred in nature, if at a generally invisibly slow pace.

The mite experiment is different from agricultural, orchid, tulip, pigeon race-horse, or pigeon breeding in that the investigators, unlike breeders, apparently didn't specify in advance what trait they were selecting for.  They let the natural genetic variation in their mites determine the responses to the crowding and unnatural dietary conditions.  But the selection was comparably intense (in one experiment, only half the introduced mites survived to reproduce), and intentionally and consistently imposed.

Second, slow gradualism is by all reasonable evidence a typical but not the only way that selection can occur in nature.  Drought, infection and so on can certainly cause rapid evolution in nature.  It just seems to be relatively unusual.  And major changes that Darwin was referring to were those that led to the production of new, complex adaptive traits--like bats flying despite having non-flying mammalian ancestors.  Mite life-span calibration differences are not like that in that there is no reason to think fundamental reorganization was required, or some novel trait.  We have vast amounts of data far more consistent with gradualism as the general pattern than with highly speeded-up adaptation, but even for the latter we have long had theoretical understand of when and how that can occur.  If life is about anything, it's about exceptions rather than rigid rules.

Third, only the most ideological Darwinist these days refuses to recognize that much of evolution occurs without any substantial, much less systematic natural selection.  Genes and the traits to which the contribute can evolve 'neutrally', changing over time just by chance.  So a modern Darwinian has to recognize that the degree of natural selection, and the tightness of adaptation are fluid, variable, and often far less deterministic than Darwin himself seemed generally to believe.   After all, he had vastly less data on time, paleontology, comparative biology, or genetics than we do today.  Anyone who sticks too closely to Darwin's own ideas (and it was the investigator himself who contrasted his results to Darwin), is like someone sticking to the Bible to explain the world:  Darwin was a brilliant world-changing scientist, but he made mistakes and the 150 years since his main work have greatly modified much of what he said. 

Scientists and the journalists who report their work seem simply unable to restrain their exaggeration.  There are many reasons for this, and we're all only human.  But it should be resisted because misrepresentation, intentional or otherwise, or misapplication of theory or even the concept of theory can be very misleading.  We should strive to do better ourselves, and to restrain our own natural tendencies to gild our work and ideas.  It's hard to do, but important.

Learning the lessons of the Land: part III

This is the third and final post on a recent article in The Land Institute's Land Report, describing advances and methods to identify and isolate desirable genetic variation in plant species, with the goal of sustainable agriculture by scientific, but efficient, methods.

This is pure modern genetics, combined with traditional Mendelian-based empirical breeding as has been practiced  empirically over many thousands of years and formally since the mid-19th century.

The discussion is  relevant to the nature and effects of natural selection, which, unlike breeding choice, is not molecularly specific and is generally weak.   That's why it's difficult to find desirable individual plants in the sea of natural variation, and why intentional breeding is so relatively effective: with a trait in mind, we can pick the few individual plants that we happen to like, and then isolate them for many generations, under controlled circumstances, from members of their species without that trait.

By contrast, natural selection seems usually to act very slowly.  Among other things, if selection were too harsh, then perhaps a few lucky genotypes would do well, but the population would be so reduced as to be vulnerable to extinction.  Strong selection can also reduce variation unrelated to the selected trait, and make the organisms less responsive to other challenges of life.  If environments usually change slowly, selection can act weakly and achieve adaptations (though some argue that selection has its main, more dramatic effects very locally).

With slow selection, even if consistent over many generations, variation arises at many different genes that can affect a trait in the favored direction.  Over time, much of the genome may come to have variants that are helpful. But they may do this silently: even if variation at each of them still exists, there can be so many different 'good' alleles that most individuals inherit enough of them to do well enough to survive. But the individual alleles' effects may be too small to detect in any practical way.

These facts explain, without any magic or mystical arguments about causation, why there is so much variation affecting many traits of interest and why their genetic basis is elusive to mapping approaches such as GWAS (genomewide association studies).  

Of course, even highly sophisticated breeding doesn't automatically address variable climate, diet, etc. conditions which can be relevant--indeed, critical, to a strain's qualities.  Molecular breeding is much faster than traditional breeding, but still takes many generations.  Think about this:  even if only 10 generations, in humans that would mean it would take250 years (the age of the USA as a country) to achieve a result for a given set of conditions.  So how could this kind of knowledge be used in humans....other than by molecular based eugenics (selective abortion or genotype-based marriage bans)--days we surely don't want to  return?

Breeders might eventually fix hundreds of alleles with modern, rapid molecularly informed methods.  But we can't do that in humans, nor as a rule identify the individual alleles, because our replicate samples come not from winnowing down over generations in a closed, or controlled, breeding population, but from new sampling of extant variation each generation, in a natural population.  

The data and molecular approaches seem similar in human biomedical and evolutionary genetics, but the problem is different.  As currently advocated, both pharma and 'personalized genomic medicine' essentially aim at  predictions in individuals, based on genotype, or treatment that targets a specific gene (pharma will wise up about this where it doesn't work, of course, but lifetime predictions in humans could take decades to be shown to be unreliable).

It's hard enough to evaluate 'fitness' in the present, much  less the past, or to predict biomedical risk from phenotype data alone, though such data are the net result of the whole genome's contributions and should be of predictive value.  So how to achieve such prediction based on specific genotypes in uncontrolled, non-experimental conditions, if that is a reasonable goal, is not an easy question.

In ag species, if a set of even weak signals can be detected reliably in Strain B, they can be introduced into a stock A strain by selective breeding.  It need not matter that the signals that only explain a fraction of the desired effect in strain B aren't detected by the mapping effort because repeated iteration of the process can achieve desired ends.  With humans, risk can be predicted to some extent, from GWAS and similar approaches. But so far most of the genetic contribution detected has been elusive, weakening the power of prediction.

In humans, the equivalent question is perhaps how and when molecular-assisted prediction will work well enough in the  biomedical context, or in the context of attempting to project phenogenetic correlations back into the deep evolutionary past accurately enough to be believable.  Perhaps we need to think of other approaches.  Aggregate approaches under experimental conditions is great for wheat. But humans are not wheat.

Chewing a bit of evolutionary cud.....

Yesterday we ruminated about the nature of self, and how that relates to the organism's sense of self, and to an observer's ideas about what the organism's sense of self might be. We can pontificate about what exists, or doesn't, but ultimately we are unable to go beyond what someone reports or our definition of self.  If an ant is not conscious, in our sense, does it have a sense of 'self'?  And if a person has consciousness, can s/he really have a sense that s/he has no self?

Cow: Wikimedia Commons

Speaking of rumination, let's ruminate a bit about the ruminant and its position in life.  The cow or bull or steer must view the world from the position of its 'self'--whatever that means in bovine experience.  As with any individual, in any species, at any time, it strives to survive, and that 'striving' is genetic in the evolutionary sense and need have no element of consciousness.  So by giving lots of milk or growing tasty meat, cattle are thriving evolutionarily.  Yes, beef cattle are killed, but we all die eventually, and by the subtle trick of offering themselves up to be killed (again, it's the act not the awareness that matter in evolution), cattle genes have incredible, almost unprecedented fitness!

With our inexcusable human arrogance, we'd say no, this is artificial not natural selection.  From our point of view, that's true: we are choosing which bovine genes are to proliferate.  But the bovine genome is fighting back, offering up genetic choices for our favoritism.  More importantly, from the point of view of cow- or beef cattle-selfs, it doesn't matter what's doing the choosing: the climate, the predators, or the agronomist.  However cattle got to be here, they are here, and as long as the environment (that is, McDonald's and Ben and Jerry's) stays favorable, cattledom will thrive.  But from the cattle's selfness perspective, it doesn't matter whether its the breeder or the weather that leads it to be so successful.  When we enter the Vegetarian Age, things may change, but so do they always for every species in changing environments.

The real difference between how cattle got here and how monarch butterflies got here is that we presume there is no conscious hand guiding 'natural' selection, whereas there is one (us) guiding 'artificial' selection.

But there are long-standing discussions about  the extent to which our past evolution channels our future--'canalization' is the classical word for this, making it somewhat predictable.  Evolution can only mold things in directions that viable genetic variation enables.  If a species' biology and genomes are so complex that only certain kinds of genetic change is viable, then there are only so many ways it can change.  That is not a conscious hand, but from the organism's viewpoint, it's not so completely different from artificial selection.

So in that sense it's we who make a distinction between our guiding hand and Nature's.  It may be worth ruminating about this, just for the fun of it, because it's a kind of human (self-)exceptionalism by which we create a difference, in our own minds, about how natural change comes about.  But 'in our own minds' means a distinction that is the result only of our own selfness.  And we tend to deny selfness to any other species.

What would all of this look like to the proverbial Martian, whose assessment machinery may bear no resemblance to 'consciousness' and who thus may not see us as being so separate from the rest of Nature's clockworks?

A new broom sweeps gene?

Today we write about a story that isn't hot off the press, but was published in Nature a few months ago, and  happens to be one of those findings that we think more people should know about:.  The issue is the genetic signature of selection, something that has become the focus of much anthropological and population genetic research with the advent of whole genome sequencing data.

What the authors did was to follow populations of fruit flies over 600 generations and comb the entire genome of 260 of them for variation after applying intense artificial selection on the measurable, and malleable, traits of accelerated development and early fertility.  They bred a population in which development was about 20% faster than in unselected populations.  The question was whether a single gene or multiple genes would be responsible for the change.

They compared the genomes of the selected and control populations with the reference fruit fly genome, and found hundreds of thousands of SNPs, or single nucleotide polymorphisms, differences between the populations.  Of these, they found tens of thousands of amino acid-changing SNPs, about 200 segregating stop codons and 118 segregating splice variants -- that is, variants that could be responsible for the phenotypic changes they had selected for.  They further narrowed down these candidate loci to 662 SNPs in 506 genes that they considered to be potential candidates "for encoding the causative differences between the ACO and CO populations, to the extent that those differences are due to structural as opposed to regulatory variants."

For the biological processes, there is an apparent excess of genes important in development; for example, the top ten categories are imaginal disc development, smoothened signalling pathway, larval development, wing disc development, larval development (sensu Amphibia), metamorphosis, organ morphogenesis, imaginal disc morphogenesis, organ development and regionalization. This is not an unexpected result, given the ACO [accelerated development population] selection treatment for short development time, but it indicates an important role for amino-acid polymorphisms in short-term phenotypic evolution.

Actually the idea that adaptive change was brought about by gene-impeding mutations (premature stop codons and splice variants, for example) is interesting.  It means that adaptive change under selection doesn't just improve function, but it may also destroy function--to pave the way to the change, one might surmise.

They went on to do a 'sliding window' comparison of regions of the genome that diverged significantly between the selected and control populations, and identified 'a large number'.

...it is apparent that allele frequencies in a large portion of the genome have been affected following selection on development time, suggesting a highly multigenic adaptive response.

The authors interpreted this work in terms of the 'soft' or 'hard' sweep idea that is often used to explain reduced gene frequencies ( a 'hard sweep' being when a single mutation quickly becomes fixed in a population, and a 'soft sweep' being when multiple genes influence a trait).  They suggest two explanations for their 'failure to observe the signature of a classic sweep in these populations, despite strong selection' (not enough time for the causative gene to reach fixation in the population, or that selection acts on standing, not new mutations).

RA Fisher

But, it wouldn't be a surprise to RA Fisher (this is a link to his Facebook page, by the way -- go friend him, he only has 6!) that the observed changes are due to polygenes.  But it is nice to see an experimental confirmation, and to note the implications it has for understanding complex traits.

Many biologists have been lured into single-gene thinking by the research paradigm and model set up initially by Mendel.  For decades single-gene traits formed the core of what we would call the evolving molecular genetics including Morgan's work on chromosomal arrangement of genes, many human geneticists' work on 'Mendelian' disease, the work leading to the idea that genes code for proteins, and much else.

Besides these examples of causal genetics, we had selection examples such as sickle cell anemia, that seemed to reflect evolutionary genetics and were due to single protein changes.  But we always knew (or those who cared to understand genetics should have known and could have) that traits were more complex than that as a rule.  Sewall Wright and others knew this clearly in the early 20th century.  'Quantitative genetics' going back basically to Darwin (or at least his 2d cousin Francis Galton) recognized the idea of quantitative inheritance and Fisher's influential but largely impenetrable (to mere mortals) 1918 paper was a flagship that reflected formally the growing recognition that complex traits could be reconciled with Mendelian genetics if many genes contributed to complex traits.

The idea that strong directional or 'positive' selection favored a single gene grew out of the Mendelian thread, but nobody in quantitative genetics (such as agricultural breeders or many working in population genetics theory) and those who understood gene networks, should have known that most of the time, especially given the typical weakness of selection, selection would not just find and fix a single allele in a single gene.

We had reason to know, and certainly know now that when a trait's effects are spread across many variable and contributing genes, the net selective difference on most if not all of them will be very small. The response to selection will be just what the fly experiments, and many others likewise, found.

In the television attention-seeking era we need melodramatic terms, and that is just what ideas like selective 'sweeps' are.  The circumstances under which a single allele will 'sweep' (watch out, here comes that broom sweeping clean!) would occur across an entire species' habitat replacing all other alleles that affect a trait are likely to be very restrictive.  We don't need terms like hard and soft sweeps, and should not be over-dramatizing what we find.  Even a hard 'sweep' at the phenotype level is typically 'soft' at the specific gene level, and usually also softly leaves phenotypic variation in the population after it's over.

At the same time, these experiments are giving us great detailed knowledge about how evolution works, when there is, and when there is not strong selection.  This supports long-standing theory and is no kind of 'paradigm shif', it's true, but it is new understanding of the details and genetic mechanisms by which Nature gets from here to there--whether it does that in a hurry or not.

Cotton wars

A few weeks ago we commented on a story in the New York Times about increasing resistance to herbicides in weeds around the world, some of it because of plants genetically modified to resist glyphosate, or RoundUp, but all of it because of the widespread use of herbicides. And we've also written about the increasing resistance to pesticides because of genetically modified plants that produce a Bacillus thuringiensis (Bt) toxin that is lethal to many plant pests. A report in Nature this week (about a paper published in Science) describes the boon the use of Bt cotton in China has been to previously inconsequential cotton pests.

Bollworm moth larvae outbreaks were particularly destructive to cotton yields and profits in the early 1990s in China, so in response, the government approved the use of Bt cotton. Currently, according to the Nature story, more than 4 million hectares of the crop are under cultivation in China. And, as a result, previously minor pests, which were once outcompeted by the bollworm, have become major problems. The Nature piece reports:

Numbers of mirid bugs (insects of the Miridae family), previously only minor pests in northern China, have increased 12-fold since 1997, they found. "Mirids are now a main pest in the region," says [entomologist Kongming] Wu. "Their rise in abundance is associated with the scale of Bt cotton cultivation."

"Mirids can reduce cotton yields just as much as bollworms, up to 50% when no controlled," Wu adds. The insects are also emerging as a threat to crops such as green beans, cereals, vegetables and various fruits.

The rise of mirids has driven Chinese farmers back to pesticides — they are currently using about two-thirds as much as they did beforeBt cotton was introduced. As mirids develop resistance to the pesticides, Wu expects that farmers will soon spray as much as they ever did.

The Science paper is apparently the first study of the effect of GM plants on non-target pests.

Our work highlights a critical need to predict landscape-level impacts of transgenic crops on (potentially) pestiferous organisms in future ecological agricultural risk assessment. Such more comprehensive risk management may be crucial to help advance integrated pest management and ensure sustainability of transgenic technologies.

It might seem odd that an ecological perspective has been lacking when decisions are made about such things as the use of pesticides or herbicides in ecological systems, whether they are introduced into plants or sprayed on fields, but a narrow view of the problem and its solution is apparently the norm.  It is not clear (to us) why removing bollworms would make space for mirids. Was it that before, there were not seats at the cotton-table for them? Whatever the answer, it adds to the importance of ecological perspectives.

But this is true of much of science. Reducing a problem to a single cause-and-effect relationship is what our methods do best, whether it's determining the metabolic effect of a single nutrient in a single food, or of a single gene, or a parenting method or a teaching technique. The unintended consequences that can result from such approaches, such as the upsurge in non-target pests, or herbicide resistant weeks, are increasingly well-documented -- and we certainly haven't discovered 'the' way to teach math.

And this is without even mentioning the obvious lesson, that artificial selection can have fast and sweeping consequences. And that when short-term gains (in the case of Bt cotton, profit) drive decision making, whatever we actually do know about long-term consequences may not even be factored in.

Perhaps, as industrial genetics is likely to argue, we are able to use technology to keep at least a half-step ahead. The definition of 'winning' in Pest vs Crop wars would be that, rather than any dream of a pest-free world. But as the human population and its demands grow, so likely will high-volume monocropping, and along with that more vulnerability. If the pace of biotechnology can be kept greater than that of artificial selection, then the current approach will work reasonably well, at least in the short term -- or that's what industrial genetics will argue. Maybe it's true -- until another ecological aspect, the toll on soil and water of monocropping, takes over.

Like any organism -- such as a human -- the human-made and human-affected world is made of many parts that exist and evolve together. Organisms can go extinct, and so can ecosystems. That is, they could change in ways that we who are responsible cannot adopt. Whether that's in the near-term offing is of course highly debated. Whoever wins....

Rounded up? No, the varmints got away!

It seems there really is no free lunch....except perhaps for weeds. That's because it turns out that genetically modified crops don't defy evolution after all! The laws of Nature stand, and weren't superseded by agribusiness scientists.

A story in the New York Times this week tells about the increasing resistance of weeds to Roundup, or glyphosate, the weedkiller originally introduced by Monsanto but now sold by a number of other companies. The weedkiller was made for use with 'Roundup Ready' crops, grown from seeds genetically modified to be resistant to the herbicide. Many farmers who planted these seeds were very happy with how easily weeds could be controlled as well as the kind of no-till agriculture, and the reduction in top soil erosion that that brought, that then became possible. (Though there was, and still is, controversy over Roundup Ready crop yields, the safety of the chemical, Monsanto's legal right to insist that farmers can't save seed to plant the following year, and so on, but those issues are not for this post.)

But farmers are growing increasingly unhappy. Roundup resistant weeds -- superweeds -- were first found flexing their new-found muscles in Delaware, but now crop up all over the country (so to speak), with insidious and expensive effects.

To fight them, Mr. Anderson and farmers throughout the East, Midwest and South are being forced to spray fields with more toxic herbicides, pull weeds by hand and return to more labor-intensive methods like regular plowing.

“We’re back to where we were 20 years ago,” said Mr. Anderson, who will plow about one-third of his 3,000 acres of soybean fields this spring, more than he has in years. “We’re trying to find out what works.”

Farm experts say that such efforts could lead to higher food prices, lower crop yields, rising farm costs and more pollution of land and water.

“It is the single largest threat to production agriculture that we have ever seen,” said Andrew Wargo III, the president of the Arkansas Association of Conservation Districts.

Oddly enough, Monsanto originally promised that herbicide resistance would be insignificant. Why? They must have believed they were dealing with so fundamental a vulnerability on the weedy pests' part that they couldn't evolve a way around their assassin.

Monsanto is still saying that the problem is containable -- but they would, since they stand to lose a lot if farmers no longer have reason to buy Monsanto's Roundup resistant seeds. Did Monsanto think that, as one of the largest agricultural companies in the world, that they could make evolution stand still? And of course it's not just glyphosate resistance that's the problem. The International Survey of Herbicide Resistant Weeds lists "347 Resistant Biotypes, 195 Species (115 dicots and 80 monocots) and over 340,000 fields". The additional problem with Roundup is that farmers (and Monsanto) have become dependent on GM seeds, and the cultivation methods they've used to grow them.

The story is of course reminiscent of the increasingly widespread antibiotic resistance in bacteria, though there we had 50 good years, while with Roundup it was only several decades -- neither even a blink of the eye in evolutionary terms, of course. But, we've known for millennia that artificial selection is a fast and powerful force for change -- it was Darwin's very model for how natural selection works in the wild, after all. Farmers have chosen their best animals for breeding probably since they were first domesticated 10,000 years ago.

So, it shouldn't be surprising that in effect artificially selecting for herbicide resistant weeds, or antibiotic resistant bacteria, is fast and effective as well. The idea that we might be headed for the last roundup is naive. Nope, the truth is, pardner, that the varmints are still out there, eluding all the posses we send after them.