Plus c'est la même chose, plus ça change??

Nothing ever really changes, or so goes the old French saying 'plus ça change, plus c'est la même chose.' The more things change, the more they're the same thing. But is that how life really is?

An interesting new paper in Genome Research on this subject is getting some notice, but in fact the results should not be surprising, given what is known about evolution and development.

The blurb in Nature says:

The earliest stages of embryo development [as shown in the photo above, taken from the paper] seem to be almost identical among mammals. However, Sheng Zhong at the University of Illinois at Urbana-Champaign and his team have found that 40.2% of the genes shared by humans, mice and cows are expressed differently at this point.

Their analysis of gene-expression patterns in embryos at various stages early in development showed that differences result from altered gene regulation. In some cases, mutations affected the binding of regulatory proteins. In others, transposons or 'jumping genes' had hopped in front of the genes, changing their regulation.

This variation among species suggests that multiple gene networks can guide embryo development, and could be harnessed to generate embryonic stem cells.

This may have significant implications for stem cell research, but it also says a lot about evolution and development (EvoDevo). People are often surprised to learn that traits that are similar between species can have very different genetic architecture -- it's more usual to hear about homologous or orthologous genes, similar genes for similar traits (the iconic example is Hox genes, which play a major role in body patterning in fruit flies and humans, and every species in between).

Alternatively, a story in the New York Times last week described the usefulness of yeast or plants or worms for finding genes for human diseases. The genes described belong to clusters that do completely unrelated things in different organisms (one example was of a cluster of genes that repair damage to the cell wall in yeast but that is involved in blood vessel formation in humans). These clusters have been conserved through evolutionary time.

But the idea that different genes can underlay homologous traits is perhaps more counter-intuitive. Ken and his then post-doc, Malia Fullerton, published a paper in Theoretical Population Biology in 2000 describing just this. The effect is called 'phenogenetic drift' to indicate that the trait's genetic basis, the genetic effects that generate the phenotype, changes. This is not the same as genetic drift, when genetic variation that has no effect on a trait, or at least on reproductive success ('fitness') changes over the generations, nor that of phenotypic drift, when traits vary over generations to the extent that the variation doesn't affect reproductive success. Phenogenetic drift can be these things, but also, and perhaps most importantly, it occurs even when there is selection affecting the trait, even strong selection.

Thus, in the example above, the very early and hence very fundamentally important, stages in mammalian embryos are quite similar among different species, but the usage of genes to make it so is considerably different. Phenogenetic drift is easy to see all over the place -- even within species, when different people can have the same trait -- even including disease -- for different genetic reasons. Relative to each other these genotypes are equivalent in fitness terms, and their contributing alleles will change frequency over time by drift. It's no surprise to see it when we know that duplicate genes and many contributing genes together generate lots of redundancy and alternative genetic pathways to get the same trait.

However the dogma about selection and adaptive evolution has been gene- rather than trait-centered. But when many different genotypes can generate effectively the same phenotype, then perhaps genes really aren't the most important things to consider when we try to understand evolution. In this sense, perhaps because genes weren't understood at the time and perhaps because he had it right, Darwin developed his ideas about phenotypes -- the traits of organisms -- rather than genotypes. After all, he didn't need his idea of genetics to explain the historical nature of life's variation (indeed, evolution as he saw it wouldn't work under his idea of inheritance, and he knew it).

It often seems that the longer a trait is maintained, the more likely it is to have changed its genetic basis. Kazu Kawasaki in our lab, for example, has written a number of papers about the different genetic architecture for bone and tooth mineralization that has evolved in different lineages. In that case, the gene pathways share a common ancestor, a single gene that duplicated in different lineages to create gene families involved in mineralization -- he calls these the SCPP gene family. The original founding gene was apparently involved in the development of the first vertebrate mineralized skeletal tissue (probably, external skeletal protective plates or scales, even before there were calcified bones).

The final composition and structure of mineralized bone may vary, but it's the same trait, and serves essentially the same purpose (strength) in different lineages. Same trait, different genes. Whether this is usually true with conservation of form within lineages (such as the ants in amber that we wrote about last week), we can't know, because we have no way to know the original genetic basis. However, among other things, phenogenetic drift or alternative genomic pathways to the same trait, has interesting implications for notions of homology, the sharing of traits today because they have descended from the same ancestor. Traits can be homologous, but their genetic basis may not be. When selection is on the phenotype, it gets maintained however works!

School's Out! (But is my joy based in biology?)

It’s the last day of the semester. Students are submitting their final exams to me today and it’s only fitting that I submit my final thoughts to them (and to you) about what I learned this semester about the Biology of Behavior (Anthropology 261).

First of all, it’s mind boggling that after spending an entire semester studying the subject there are students on one hand…

Here’s me with arms outstretched to the sides, palms up.

… who believe that behavior is mostly determined by genes and that one day we’ll be able to explain it all with genetics, and then there are students on the other hand who are super critical of science and also think that behavior is entirely learned.

You’re wondering what this “behavior” is that I’m talking about.

Me too.

Here’s me wincing vulnerably with blushing cheeks.

That’s problem number one. What is behavior? It’s not really clear. Not after a course like this. Maybe my students will illuminate this for me in their final essay in which they categorize human behaviors according to their own taxonomies. But I haven’t read their essays yet.

Here’s me feeling fight-or-flight grading anxiety with tingly palms and armpits.

Problem number two. Everybody, even the most extreme, was on board with Nature PLUS Nurture (as opposed to Nature VERSUS Nurture). So, many of the class discussions boiled down to popular debates, as opposed to more nuanced debates that would have been more productive. But because we couldn’t become experts at this introductory level, it was difficult to get to the nitty-gritty. What we concluded was that the debate about human behavior in the popular media is full of false dichotomies, irrational fears of improbable/impossible future science, and irrelevant debates as a result of both.

Problem number three has to do with normal versus abnormal behavior. People seem to think that because a behavioral disorder can be traced back to genes, then therefore variation in that behavior at the normal level in unaffected people can also be explained by genes.

Here’s me making a wrong answer buzzer sound. Errrrrrr!

So did we figure out why humans do what they do? Well, considering the two choices [(A) It’s instinct. It evolved by natural selection or (B) We learned it. It’s a product of our environment.] The question of why becomes obscured by the possibility that we may not have a choice.

The former choice, A, implies that we can’t help our behavior…We have excuses for behaving badly and we can’t take moral credit for behaving nicely either.

The latter, B, puts the emphasis on culture and its importance…either at the individual level or beyond. Our bad behavior is our own fault or due to our parents, friends, environment, circumstances. Our good behavior is our own doing or it is shaped by parents, friends, environment, circumstances, and by government laws and religion.

So no matter what the answer is, it’s probably going to offend somebody.

Then there are all the behaviors that are neither “bad” nor “good.” The ones that are just what folks do or do not do at various times of their lives, in various circumstances, under various conditions, according to various individual biologies and histories.

Here’s me shrugging my shoulders and throwing my hands up in the air.

The bottom line that everyone agreed on (I hope) is that all behavior is biological even if it’s learned because we are biological beings. Everything we do, learn, say, feel, think is a biological process. Our genes don’t have to determine it for it to be biological. And, it’s all biological unless you invoke supernatural explanations. Human behavior is biological and this goes for whether or not we intend to do what we do.

So what are the determinants of human behavior that all somehow derive from biological processes?

We made a flow chart over the course of the semester and this is the result. Because there are no arrows pointing to any behaviors, this is not a chart of the determinants of human behavior. Instead it is the “Determinants of the determinants of human behavior.” Smart alecs will notice that there are no quantum variables on here and that’s because we didn’t get that small/big this semester.

Hey, at least it’s better than the flow chart for the American strategy in Afghanistan.

Now could you say that explaining human behavior is easier than explaining the American strategy in Afghanistan? That's a good question! But this flow chart may have caused you to wonder, what’s the point of trying to explain human behavior if it’s at least this complex?

Well, there are behavioral disorders we can hope to treat or cure. And there are evolutionary puzzles that we want to solve!

So how’s the treatment of disorders going? One recent example is the search for the genes for stuttering. That the genes linked to stuttering are involved in metabolism is, first of all, surprising to most until they think about how metabolic processes are linked to neurological development. Okay. So what’s the gene? There are three genes where stutterers in the study population had mutations: GNPTAB, GNPTG , NAGPA. So they found the genes for stuttering? Not exactly. Only 6% of stutterers in the sample had these mutations. Only 6%! The other 94% of stutterers are stuttering with perfectly normal versions of these genes. Plus, there are some people in the sample of non-stutterers (albeit a very few, <0.5%). style="">At least for the 6% who do have known mutations, they could see drug treatments soon.

Now, about those evolutionary riddles we’re all dying to solve…

That’s where maternal effects come into play. This is when mom’s genotype or phenotype influences her offspring’s phenotype and maternal effects are known for things like body size, immune function, predator resistant morphology (like spikes or wings). Known triggers are things like resources, density of conspecifics, temperature, parasites, and predators. And these are adaptive! Relatively little is known about maternal effects on behavior, however, it has been reported recently that mother crickets, just by their being around wolf spiders, influence how their offspring react to predators.

Here’s me crouching down and imitating a cricket immobilizing itself as predator-defense.

Mothers who have been exposed to predators have offspring that are better at surviving in the presence of predators than offspring of mothers who have not been exposed to predators.

Here’s me spit-taking my morning coffee because this is just so incredibly mind-blowing.

So if Nature VERSUS Nurture is so passé. And if it all does boil down to biological underpinnings and genes even if the genes don’t dictate things. Then why the rage and the frustration over explaining human behavior? Why the fears that we’re going down the horrific eugenics path by continuing to search for genes for behavior when we probably can’t find genes that determine variation in any of the behaviors that we find especially interesting in normal people?

I think that what offends people most about biological studies of behavior is the simple fear that it might be explained. Learning about human nature and coming up with the explanations for ourselves, by ourselves, is one of the thrills of being a human. It’s something that we want to experience over our lifetimes, not learn from someone else’s simple rules. It’s the idiosyncrasies and the surprises along the way that can be so beautiful and meaningful and those moments are threatened if a scientist tells us how to size up a person with an equation.

What I learned this semester is that people are defensive about science explaining our personalities, our selves. But what I also learned is that no matter how hard it tries, science cannot explain even the average Joe’s behavior or personality with genes or otherwise.

So what’s the big deal? Relax. You’ll always be somewhat of an enigma. And so will I.

Here’s me lifting my arms behind my head, leaning back, grinning, and sighing contently.

School’s Out!

Another jolt to keep you awake at night

American epidemiology follows our puritanical culture, and intensely focuses on how harmful anything fun must be for you. Coffee, tea, alcohol, McFastFood, sugar, salt, chocolate, and sex (especially sex) are the Devil's own work. After all, when did you last see a big, expensive epidemiological study designed to show that brussels sprouts, rudabegas, or other delicacies of that sort are harmful. No--sin which means pleasure, is harmful. Must be harmful!

But here's a shocker: the latest bulletin from the Professor Sez One Food Fits All Department claims that coffee may be good for you (after all), and in so many ways! Now, after years of how bad it was for you, course is reversed by this deeply insightful, highly technical, perceptive study.

Now, it's too easy to poke fun at epidemiology (even genetic epidemiology) and the media, hand in hand with Claims of the Day. It's a major theme of this blog, since we try to be entertaining, and silly science is always good for a few laughs.

But another, actually serious, side of our blog is to comment on how science is working and at least to argue that it ought to be reformed. The first big problem is that reform involves several sticky wickets: how to disengage our professional careers from dependence on hasty results, self-marketing, grant-based salaries and tenure, proliferating competition and all. Those are all too human factors.

The other big problem is that the topics we're all trying to chase are damned difficult. You can't manage a career easily these days and still have time to try--really try--to wrestle with the general question of understanding multifactorial complexity without taking reductionist approaches, and usually hasty ones at that.

This latest Big Finding about coffee means that you'll live longer, with fewer diseases of all sorts, but in two ways. You'll not die of the typical diseases, which will add years to your life (if not hairs to your head or inches to your waistline). And you'll live more before you're dead because if you dose up on coffee you'll have fewer hours of sleep to waste your life away in. But you may have to accept feeling dead tired instead, as you lie wide awake all night thinking how great it is to still be alive. And, being tired, you'll be more accident prone, and .... well, there's a damnable trade-off to everything, it seems!

We have no solution (not even decaf). We wish we did. But if we did, we'd not have time to blather on in a blog like this. So maybe Silly Science is good for us, too!

Chocolate madness, chocolate sadness

Well, folks, here's another installment for the law of unintended consequences, or the life's not as simple as you wish it were logbook. For years, the chocolate industry has been sponsoring research that showed that cocoa butter was good for your circulating lipid levels, and hence good for your heart. The Miracle Elixir, chocolate has even been shown to prevent cavities. Great news for those with chocolate madness, restaurants serving double or triple chocolate cakes, and great news for those looking for warm, loving Valentine's day gifts! Eat up, slim down, live longer, and love.

Unfortunately, there's a spoil-sport in every crowd. A BBC story throws a wet blanket on chocolate mania. It appears that rather than cheering you up, chocolate is a real downer. Maybe (hopefully) that's why your Valentine burst into tears and said s/he didn't really want to be your Valentine after sampling from the Lady Godivas you gave er.

It may be less than a shock to learn that the vast Cocoa-conspiracy of Hershey-funded researchers didn't happen to report this side of things. But they may not have bothered to look at what, for the researcher and his/her grant prospects, would be too saddening. Now, of course, the discoverers of this new effect say -- surprise! -- that more research is needed, so we can find out whether chocolate causes depression, or chocolate eaters are already self-medicating when the epidemiologists show up!

What is the reason for this? It's the way science works and is rewarded (not with chocolates!). It's the scientific method, that 'tunnels' through complex traits by intentionally keeping as many constant as possible so the effects of one only is studied. See our earlier posts on 'tunneling' and the philosophy of science. The problem is that when we do this, we intentionally ignore the other factors that also are at play in the real world. We know this, but we run to the BBC or NYTimes with our findings anyway.

It's sad enough that the pharmaceutical industry is trying hard to get all of us on lifetime maintenance medication: tranquilizers, neurotransmitter (IQ) boosters, statins (lower cholesterol), and who knows what else. So we see lots of advertising to push this. It's great for business. But the chocolate industry has itself been trying to push its products essentially as maintenance medication (eat a lot of it, every day, your whole life long, to prevent depression and heart disease). Pretty disgusting (the idea, if not the chocolate).

Please pass the cherry pie!

Henrietta Lacks privacy

A piece in the Sunday New York Times by Amy Harmon, "'Informed consent' and the ethics of DNA research", discusses the issues brought up by the recent case of the Havasupai vs. the University of Arizona (which we posted about here). Can anything be done with DNA samples once the original purpose for which blood was collected, and for which researchers had consent, has been accomplished?

Legally, we have no property right to our cells or tissues once they've left our bodies. But, researchers with federal funding are required to inform subjects what they are going to do with the samples, as a condition of getting the samples. Nowadays, that means everything they plan to do with them, for however long the samples are archived. And that includes the use of unforeseen technologies to look for as of yet unpredictable kinds of information.

This issue is not new, and in fact a sixty year old story about this is described in a recent book by Rebecca Skloot called The Immortal Life of Henrietta Lacks. Ms Lacks was a young African American woman who had the misfortune to have a particularly fast-growing form of cervical cancer, diagnosed in the late 1940s. She died in 1951, at the age of 31. She had been treated at Johns Hopkins, in Baltimore, where one George Otto Gey was then attempting to immortalize cell lines, so was collecting whatever tissue samples he could in his effort to perfect the technology for doing this.

Only when Gey's technician tried to grow cells from a sample of Ms Lacks' tumor were they successful. The significance of this was quickly apparent, and cell lines were immediately distributed throughout the medical world to be used in such research as the polio vaccine, and much more. The cells from Ms Lacks' tumor, and/or the DNA, are still in use in labs all over the world.

Neither Gey nor Hopkins ever profited from this work, but the sample was taken without Lacks' knowledge or permission. This was state-of-the-art at the times. Indeed the courts have recently ruled that samples can be used without the patient's permission or knowledge, even for profit (in a case decided by the Supreme Court of California, Moore v. Regents of the University of California.)

In her book, Skloot describes how she became fascinated by Henrietta Lacks in a biology class she took as a teenager, but was frustrated to discover that very little was known about her. Or perhaps she was fascinated because there was so little known. In any case, Skloot eventually decided to write a book about Lacks, and she spent much of her 30s looking for whatever information she could find. That turned out to be not much. So, she turned to Ms Lacks' surviving children and other family members to try to piece together the story of their mother's life.

Actually, by Skloot's own description she hounded Ms Lacks' children until they finally agreed to talk with her -- in one case, it took a year of frequent phone calls. And she fills her book with everything she learns about this woman and her family who, it turns out, are living largely in poverty in Baltimore, Maryland. Because Ms Lacks died young, and in poverty, the artifacts of her own life are few, and because she died when her children were so young, they remember little to nothing about her. So Skloot delves (intrudes?) into the lives of the children, and tells about a murder, sexual abuse, their religious practices, their scientific beliefs and many other heretofore private details. The book is being very well reviewed, and is selling like hotcakes.

But why? As with the Havasupai, Ms Lacks' family members learned by accident that Henrietta Lacks cells were in such wide use. According to Ms Skloot, that knowledge made them feel both that their mother must have been special and that she was being exploited. But, their mother's life is being conflated with the circumstances of her death; the particular tumor she had, and being in the right place at the right time with respect to the development of a particular technological advance. Or indeed, the wrong place at the wrong time, with respect to her privacy and the privacy of generations of her family to come.

To us, there's nothing about this story that would suggest that the world needs, or has a right to know any of the details about the lives of Henrietta Lacks or any member of her family. This book just continues what Ms Lacks' children originally saw as exploitation of their mother by a world out to make a buck. While Skloot has set up a foundation for the Lacks family with some of the proceeds of the book, this book is still poverty tourism, and it rights no wrongs.

You look just like your grandma, Or, Why conservation poses challenges for evolutionary biology

We posted last week about the 95 million year preservation in amber of plants and insects in recently discovered samples of ancient amber in Africa. This showed the early distribution of recognized types of organism very long ago in Africa, affecting reconstructions of paleoecology, since at least some had not formerly been known to be there.

That was interesting, and we raised another broader point that these specimens showed. It has to do with the conservation of form over evolutionary time. It's one thing to look like your granny, and quite another to look like your 95-million-times-great granny!

The evolutionary problem (and it's not a new one nor one we invented) is to explain the very ancient existence of species that look strikingly, perhaps entirely, those alive today. If (as we recently discussed) even a few hundred thousand years is enough for anthropologists to insist on naming a fossil as a new species--or even genus!--then how can something 95My old look so strikingly like what we see today?

One might think that insects, because they have a smaller genome than vertebrates, have less genetic 'room' for variation, and are more constrained by selection so that organisms like flies have no variation left--no ability to viably change form. Bacteria have maintained their form since literally the most ancient of times (fossils called stromatolites, ~3Bya old). But even bacteria have multiple genes contributing to traits, and insects and plants certainly to, too. Selection studies in these types of organisms, and mapping studies on even such exotic traits as startle reflexes, wing venation, bristle count, and sleep habits in flies show genetic causal complexity due to existing variation in their natural populations.

Thus, with many contributing genes, each susceptible to variation, one might expect plenty of room to vary, ever so slightly, over millions of years. Furthermore, these groups have continued to evolve diverse species so that there wasn't just one way, say, to be a fly that, once installed, was so tightly fenced in by natural selection as to be preserved for time immemorial. In genetic terms this would generally called an adaptive peak on the genetic fitness landscape, that the species simply couldn't get off. But this is a post-hoc argument that seems just too pat, without some further justification (speculation about this has certainly been offered, but is difficult to prove).

Anyway, the conservation of form and function, as well as its adaptive evolution present important problems that are not yet fully solved. You look a lot like your granny, and we have a clear understanding of why that is. But you don't look exactly like her, and for a fly or fern to look like its countlessly-great-great grannies is harder to explain.

With great power there must also come great responsibility

You’ve probably already forgotten about A. sediba.

After all, it’s been just over two weeks since the two new gorgeous partial skeletons from Malapa, South Africa were unveiled in Science magazine. And, after all, you’re probably a normal person who can forget about extinct hominins between their media splashes.

But there are some people who cannot.

They are a dedicated brother- and sisterhood of scientists who work around the clock on our fossil record. Adding to it, maintaining it, and interpreting it. It’s only because of this fearless gang of fieldworkers and phylogeneticists that you can live a relatively luxurious, paleoanthropology-free lifestyle.

Really. They never stop working for you.

In fact, just after the new species was announced, paleoanthropology’s two most important conferences (the annual meetings of the Paleoanthropology Society and the American Association of Physical Anthropologists) were held in St. Louis and in Albuquerque just so that hundreds of us could put our brains together, meld our minds, and figure out just what to make of these bones. If you say it’s just a coincidence that these conferences occurred mere days after the Science publications, well then you just don’t understand the extent of paleoanthropology’s superpowers.

Both Lee Berger and Darryl de Ruiter gave spectacular back-to-back presentations at the Paleoanthropology Society meetings on the Malapa fossils. Afterwards, the floor was opened up for questions. Because I am a real blogger and am not just using it as a convenient cover for another more mysterious occupation, I raised my hand, “How do you know the arms are long?”*

From the gist of Berger’s answer and from what it says in the paper, although the drawing shows the arms to be long, the actual length of the arms relative to body size is not a shut case. However, with the additional remains from more individuals still lying there, in the ground, just waiting their turns to be excavated…. Good estimates of body and limb proportions are tantalizingly close!

Not only that, but word on the street is the preservation is so tremendous that there may be organic remains beyond bones and teeth—the actual squishy parts like hominin skin and hair and who knows what else? If this is true, start bracing yourselves for a paleoanthropology story that will eclipse the hobbit! In fact, by all accounts, Berger and his team are at the site right now—while we’re just going about our normal daily lives—working hard to recover all the additional remains.

Among paleoanthropologists, there are many questions about the Malapa remains. Some question the dating (could be younger than they say!), but the general buzz seems to center on the genus. Why Australopithecus and not Homo or not something else?

An equally valid question is who cares? After all, Mother Nature wouldn’t know a genus if it smacked her in the face. Genus is important to humans alone. The genus that we use to label the Malapa specimens stands for how we interpret them. If they were Homo, they’d have to be more cognitively complex than australopiths, making stone tools, eating a more diverse diet that included meat from scavenging and hunting, walking and running with completely bipedal bodies, etc…. But as australopiths, with their tiny brains and mosaic of bipedal and arboreal (or remnant arboreal) morphology, they’re one step behind Homo—even if they’re 1.9 mya or younger and even if they overlap in space and time with early Homo.

Get ready for a complete overhaul of how the Plio-Pleistocene transition in the hominin fossil record is interpreted. Using standards that were implemented back in the 1960s when the fossil record made much more sense (because there were so many gaps!) is no longer appropriate let alone feasible.

What is easily forgotten in exciting times like these is that each new fossil that paleoanthropologists uncover will look different from all others. That’s because of variation due to sexual reproduction among other things. So the notion that something is special because it looks like nothing else we’ve ever seen before is misleading. Malapa is certainly special but clones of previously known hominins? Now THAT would be special. The trick is to know just how different something is, if it’s just normal variation within a species (with some change through time accounted for) or if it’s too much variation for within one species. If it’s the latter, then it’s a new species.

In this case, the authors have decided that the Malapa remains are too different from A. africanus and from anything else on record. And so a new legend is born and a new name, A. sediba, is added to the roster of those who make the world of paleoanthropology the most exciting realm of all!

Probably an even bigger to-do than the scientific reports on Malapa was the openness of the researchers. They brought casts of all the material and laid them out for everyone to see, plus they offered to make casts for anyone interested. Having just discovered the fossils in late 2008, this is a laudable strategy for moving paleoanthropology in a productive direction. If people are going to keep finding all these rewriting-the-textbook fossils, then getting them out quickly for the rest of the gang to see, by Berger’s team’s example, may be standard practice from here on out.

And on that note, I leave you with this final thought.

Whenever you or someone you love gets excited about a hominin fossil, whenever you fall asleep at night assured that your hominin ancestors are being respectfully reconstructed, whenever you walk safely down the street knowing that your evolutionary tree is growing properly, don’t forget to thank your friendly neighborhood paleoanthropologist.

This superhero-themed post is dedicated to my student Samantha Davis who presented a terrific poster on early Homo molar shape outline at the Paleoanthropology meetings. If only we’d had Malapa to include in the analysis, right?

*What I should have asked when I briefly had the floor back in that ballroom was, “Can we eat it?” After all (according to my cab driver from the airport who just finished Voyage of the Beagle), until recently, when scientists found a new species that was their first question. Then if they couldn’t eat it they had to figure out what else to do with it.