To the left is a figure which illustrates the phylogenetic inferences from a new paper in Nature Communications, The genomics of selection in dogs and the parallel evolution between dogs and humans (see Carl Zimmer’s coverage in The New York Times). Why is this paper important? The first thing that jumped out at me is that because they’re using whole genomes (~10X coverage) of a selection of dogs and wolves the results aren’t as subject to the bias of using “chips” of polymorphisms discovered in dogs on wolves (see: Genome-wide SNP and haplotype analyses reveal a rich history underlying dog domestication). The second aspect is that the coalescence of the dog vs. wolf lineage is pushed further back in time than earlier genetic work, by a factor of three. A standard model for the origin of dogs is that they arose in the Middle East ~10,000-15,000 years ago , possibly as part of the broad shift of lifestyles which culminated in the Neolithic Revolution.
This model is now in serious question. Though there have always been claims of fossils of older domestic canids (adduced as such in terms of morphology) than the ones discovered in the Middle East ~15,000 years ago, this year there has been publication of ancient mtDNA results from ~30,000 years before the present which imply the separation of putative domestic and wolf lineages at least to that date. Over the past few years I have wondered about the specific nature of the emergence of both modern humans and modern dogs, and their co-evolutionary trajectory, over the Pleistocene and into the Holocene, in light of these results.
What a great age we live in. Until recently critical parameters in population genetics such as mutation rates had to be inferred and assumed, even though they served as bases for much more complex inferences. Now with humans (and humans are only the beginning!) much of what was inferred is being assessed in a more direct fashion. Caterina Campbell and Even Eichler have a review in Trends in Genetics which surveys the field as it stands now, Properties and rates of germline mutations in humans. Notice that there’s a rough convergence using pedigree analysis of a mutation rate in the low 10-8 range. Additionally, it does seem that a disproportionate number of novel mutations come through the paternal lineage via sperm. This should increase our moderate worry about older fathers (something reiterated in the piece, with caveats). Finally, the authors suggest these results are a floor for the mutational rate, in part due to the long term conflict with the inferred ‘evolutionary rates,’ which are higher. This matters because to infer the last common ancestors between lineages the value of the mutation rate is obviously critical.
E. O. Wilson has a op-ed in WSJ which I find quite interesting, Great Scientist ≠ Good at Math:
For many young people who aspire to be scientists, the great bugbear is mathematics. Without advanced math, how can you do serious work in the sciences? Well, I have a professional secret to share: Many of the most successful scientists in the world today are mathematically no more than semiliterate.
This imbalance is especially the case in biology, where factors in a real-life phenomenon are often misunderstood or never noticed in the first place. The annals of theoretical biology are clogged with mathematical models that either can be safely ignored or, when tested, fail. Possibly no more than 10% have any lasting value. Only those linked solidly to knowledge of real living systems have much chance of being used.
Wilson has been on this for a bit now, to the bewilderment of some of the scientists I follow on Twitter (granted, the people I follow tend to be quantitative genomics types whose backgrounds may have been in math, physics, or statistics). Two immediate things come to mind reading this. First, a disproportionate number of the famous and successful scientists alive today are old, like E. O. Wilson. Just because you could get by with a certain level of mathematical fluency as an enfant terrible in the 1970s does not mean that that will cut it in the 2010s. Great scientists who are mathematically weak often have collaborators, post-docs, and graduate students, who do their bidding. It might be a different matter if you aren’t one of the Great Ones of the earth. From what I can tell scientists who are doing the hiring who don’t have mathematical skills prefer candidates who do have mathematical skills.
One could argue that William Donald Hamilton is one of the most prominent scientific figures who has been influential upon the public understanding of the world around us, who the public nonetheless is totally unaware of. Many well educated individuals with an interest in science have some understanding of the concept of inclusive fitness, at least in an inchoate sense. And, there is also an awareness that sex is somehow a biological conundrum, with the Red Queen hypothesis stepping into the explanatory void (amongst others). Hamilton’s standing within science is without question, and it was externally validated by his being awarded the Crafoord Prize, which attempts to fill in the disciplinary gaps in the Nobel awards. And yet to the world at large he is a shadowy entity in the diffuse and anonymous background of science from which writers draw their source material.
Hamilton’s influence was particularly strong upon the popular expositions of evolutionary biology of Richard Dawkins and Matt Ridley. His theories as to the origins of altruism shaped how E. O. Wilson and Robert Trivers viewed the question more broadly. Finally, one could argue that the Hamiltonian paradigm was one of the primary sources of antagonism for Stephen Jay Gould and his relationship to adaptationism and the biological basis of human behavior. Hamilton’s scientific opinions were complex, and too often they have been reduced down to inaccurate essences. This is somewhat evident in Hamilton’s own collections of papers, especially the first volume, Narrow Roads of Gene Land: The Evolution of Social Behavior. The legend of Hamilton’s framework for inclusive fitness had had many decades to mature and twist into shapes which the creator did not necessarily agree with, and he attempted to set the record straight where he thought it appropriate (e.g., inclusive fitness is not just about the origin of eusocial insects). In Nature’s Oracle Ullica Segerstrale extends Hamilton’s own reflections, and introduces a more objective third party observer into the process of evaluating the historical arc of scientific production of this one particular man.
My friend Aziz Poonawalla* asked me to comment on this piece in The New Scientist, The father of all men is 340,000 years old. My primary thought: the title probably confuses people, while the article itself is quite serviceable.The first paragraph condenses the specific and precise scientific detail well:
Albert Perry carried a secret in his DNA: a Y chromosome so distinctive that it reveals new information about the origin of our species. It shows that the last common male ancestor down the paternal line of our species is over twice as old as we thought
In the post below I alluded to the views of R. A. Fisher. This was a moderately dangerous move on my part because many of Fisher’s views have been transmitted only through later researchers, who may have lacked a clear understanding of what Fisher himself was trying to say. Heap on top of that the reality that the debate between Fisher and Sewall Wright was often abstruse for the evolutionary biologists who nevertheless managed to take sides and transmit their understandings of the conflict, and it’s a recipe for misrepresentation. With that in mind let me enter into the record an email from a friend who has engaged in a deep reading of Fisher, and attempted to understand his reasoning (no, this is not A. W. F. Edwards!):
By this time I’m sure you’ve encountered articles about the reconstructed last common ancestor of all placental mammals. Greg Mayer at Why Evolution is True has an excellent review of the implications, along with a link to a moderately skeptical piece by Anne Yoder in Science. Yoder’s piece is titled Fossils vs. Clocks, while the original paper is The Placental Mammal Ancestor and the Post–K-Pg Radiation of Placentals. The results clearly support the “Explosive Model” in the figure to the left for the origination of placentals. That might prompt the thought: “isn’t this what we knew all along?”
The standard story for the last generation in the popular imagination is that a massive asteroid impact was the direct cause of the extinction of all dinosaurs (and of course a host of other groups) except the lineage which we now term birds. And yet it turns out that there is actually some debate about this, though at least in some form it seems likely that the impact is going to be important (see this Brian Switek piece for exploration of this issue, and the general opinion of the scientific literature as of now). The second aspect to focus on is timing. Contrary to the intuition of many, over the past 20 years molecular phylogenetics has inferred a very definite (on the order of tens of millions of years) pre-K-T boundary coalescence for the common ancestors of the disinct mammalian lineages. A plausible explanation for this is that these lineages diversified through allopatry, as the Mesozoic supercontinent fragmented. Morphological diversification of these mammalian lineages also may have occurred after the K-T event.
Haldane’s Sieve points me to a new pre-print, Genetic draft, selective interference, and population genetics of rapid adaptation. Though mathematical, it’s eminently readable, and I commend it to anyone who has a passing interest in evolutionary genetics. As I am still digesting it I won’t say much more, aside from the fact that it seems to imply the proposition that neutral models of genetic variation and history may not suffice in many cases as a map of reality. This is important because these neutral models are often the null background against which one tests other alternative hypotheses.
A few days ago I was browsing Haldane’s Sieve,when I stumbled upon an amusing discussion which arose on it’s “About” page. This “inside baseball” banter got me to thinking about my own intellectual evolution. Over the past few years I’ve been delving more deeply into phylogenetics and phylogeography, enabled by the rise of genomics, the proliferation of ‘big data,’ and accessible software packages. This entailed an opportunity cost. I did not spend much time focusing so much on classical population and evolutionary genetic questions. Strewn about my room are various textbooks and monographs I’ve collected over the years, and which have fed my intellectual growth. But I must admit that it is a rare day now that I browse Hartl and Clark or The Genetical Theory of Natural Selection without specific aim or mercenary intent.
Like a river inexorably coursing over a floodplain, with the turning of the new year it is now time to take a great bend, and double-back to my roots, such as they are. This is one reason that I am now reading The Founders of Evolutionary Genetics. Fisher, Wright, and Haldane, are like old friends, faded, but not forgotten, while Muller was always but a passing acquaintance. But ideas 100 years old still have power to drive us to explore deep questions which remain unresolved, but where new methods and techniques may shed greater light. A study of the past does not allow us to make wise choices which can determine the future with any certitude, but it may at least increase the luminosity of the tools which we have iluminate the depths of the darkness. The shape of nature may become just a bit less opaque through our various endeavors.
The Pith: Natural selection comes in different flavors in its genetic constituents. Some of those constituents are more elusive than others. That makes “reading the label” a non-trivial activity.
As you may know when you look at patterns of variation in the genome of a given organism you can make various inferences from the nature of these patterns. But the power of those inferences is conditional on the details of the real demographic and evolutionary histories, as well as the assumptions made about the models one which is testing. When delving into the domain of population genomics some of the concepts and models may seem abstruse, but the reality is that such details are the stuff of which evolution is built. A new paper in PLoS Genetics may seem excessively esoteric and theoretical, but it speaks to very important processes which shape the evolutionary trajectory of a given population. The paper is titled Distinguishing between Selective Sweeps from Standing Variation and from a De Novo Mutation. Here’s the author summary:
Considerable effort has been devoted to detecting genes that are under natural selection, and hundreds of such genes have been identified in previous studies. Here, we present a method for extending these studies by inferring parameters, such as selection coefficients and the time when a selected variant arose. Of particular interest is the question whether the selective pressure was already present when the selected variant was first introduced into a population. In this case, the variant would be selected right after it originated in the population, a process we call selection from a de novo mutation. We contrast this with selection from standing variation, where the selected variant predates the selective pressure. We present a method to distinguish these two scenarios, test its accuracy, and apply it to seven human genes. We find three genes, ADH1B, EDAR, and LCT, that were presumably selected from a de novo mutation and two other genes, ASPM and PSCA, which we infer to be under selection from standing variation.
The dynamic which they refer to seems to be a reframing of the conundrum of detecting hard sweeps vs. soft sweeps. In the former you case have a new mutation, so its frequency is ~1/(2N). It is quickly subject to natural selection (though stochastic processes dominate at low frequencies, so probability of extinction is high), and adaptation drives the allele to fixation (or nearly to fixation). In the latter scenario you have a great deal of extant genetic variation, present in numerous different allelic variants. A novel selection pressure reshapes the frequency landscape, but you can not ascribe the genetic shift to only one allele. It is no surprise that the former is easier to model and detect than the latter. Much of the evolutionary genomics of the 2000s focused on hard sweeps from de novo mutations because they were low hanging fruit. The methods had reasonable power to detect them (as well as many false positives!). But of late many are suspecting that hard sweeps are not the full story, and that much of evolutionary genetic process may be characterized by a combination of hard sweeps, soft sweeps (from standing variation), various forms of negative selection, not to mention the plethora of possibilities which abound in the domain of balancing selection.
Many of the details of the paper may seem overly technical and opaque (and to be fair, I will say here that the figures are somewhat difficult to decrypt, though the subject is not one that lends itself to general clarity), but the major finding is straightforward, and illustrated in figure 4 (I’ve added labels):
Who to trust? That is the question when you don’t know very much (all of us). Trust is precious, and to some extent sacred. That’s why I can flip out when I realize after the fact that someone more informed than me in field X sampled biased their argument in a way they knew was shady to support a proposition they were forwarding. What’s the point of that? Who cares if you win at a particular bull-session? You’re burning through cultural capital. And not that most of my interlocutors care, but I’m likely to never trust them again on anything.
In any case, this came to mind when I ran across a James Fallows’ post at The Atlantic. Here’s a screenshot of the appropriate section, with my underlines:
PNAS has a paper on barley domestication out right now. It is nicely open access, so read it yourself, and come right back! I have to admit that I did not like the paper too much. It seemed to derive far too many conclusions from a few rudimentary (for today at least) phylogenetic methods. In particular I’m very skeptical of the idea that there are two barely lineages here which diverged ~3 million years B.P. But this isn’t particularly strange when it comes to the phylogenetic origins of cultivars. There have been long debates about whether there was one origin for rice, or several. Setting aside my major issues with this paper I wonder if perhaps our expectations and prejudices derived from the fact that animals are to a great extent the “null” organisms are muddying our interpretation of results from plants. The number of loci here seem sufficient to dismiss the possibility of introgression, but I’m not sure that the rate of evolution across these markers is quite so clock-like.
In any case, to understand domestication, and I suspect human evolution, these results from plants are going to have to be cleared up and systematized. Illumination would be helpful, but until then I suppose we keep on hoping that the papers keep flowing.
One of the weird things about genetics is that it encompasses both the abstract and the concrete. The formal and physical. You can talk to a geneticist who is mostly interested in details of molecular mechanisms, and is steeped in structural biology. For these people genes are specific and material things. In contrast there are other geneticists who focus more on genes as units of analysis. In this case genes are semantic labels for the mediators within an intersection of phenomena. Recall that genetics predates the knowledge of its concrete substrate by 50 years! By the 1920s Mendelian genetics had been fused with evolutionary biology to create a systematic framework in which we could understand the patterns of inheritance across the generations. In the 1950s the DNA revolution was upon us, but as W. D. Hamilton recalls this had only a minimal impact on the evolutionary genetic thinkers of the era. With the Lewontin and Hubby allozyme paper in the mid-1960s this sort of benign disciplinary evasion was no longer possible; the field of molecular evolution came into its own.*
Today with genomics these human-imposed artificialities are fading away. Consider the concept of genetic recombination. Originally an abstraction in a formal Mendelian system, today it is of great interest to molecular biologists who are curious as to its exact mechanism and purpose, and genomicists who are interested in the constraints upon the phenomenon due to its physical parameters (e.g., recombination hotspots). If we were to discover alien beings I assume that there would be some sort of genetics in an abstract sense. But would they package their genes in chromosomes? Would their complex organisms tend toward dioecy? I wouldn’t be surprised if the genetics of alien species have their own particular kinks subject to the contingent nature of the physical scaffolding of the process.
Jerry Coyne alerts me to the fact that Ullica Segerstrale’s Nature’s Oracle: A Life of W. D. Hamilton is finally near publication. Specifically, early 2013. Coyne has looked at he pre-publication text, so it is probably in revision, though the meat has already been laid upon the bones. Hamilton was one of the preeminent evolutionary biologists of the second half of the 20th century. Though to my knowledge he never wrote an autobiography as such the details of his life was liberally strewn out across dozens of books. You can find them in Segerstrale’s Defenders of the Truth: The Sociobiology Debate, or The Darwin Wars. He makes a cameo appearance in Robert Trivers’ Natural Selection and Social Theory, as well as The Price of Altruism, a scientific biography of Hamilton’s collaborator George Price.
Implicit in the title The Origin Of Species is the question: why the plural? In other words, why isn’t there a singular apex species which dominates this planet? One can imagine an abstract system where natural selection slowly but gradually sifts through variation and designs a best-of-all-replicators. And yet on the contrary it seems that our planet has exhibited an overall tendency of going from lower to higher diversity. The age of stromatolites may be the last epoch when we had the best-of-all-replicators.
A few people have emailed me about this article in The Washington Post, U.S. pushes for more scientists, but the jobs aren’t there. Other people cover this area well (for example), so I’m not going to say much. But first, ignore the article in the paper, and read the original survey which the article is based on: Science & Engineering Labor Force.
Forgot to highlight one of the coolest abstracts from SMBE 2012, A genomewide map of Neandertal ancestry in modern humans:
2. The map allows us to identify Neandertal alleles that have been the target of selection since introgression. We identified over 100 regions in which the frequency of Neandertal ancestry is extremely unlikely under a model of neutral evolution. The highest frequency region on chromosome 4 has a frequency of Neandertal ancestry of about 85% in Europe and overlaps CLOCK, a key gene in Circadian function in mammals. The high frequency, Neandertal-derived variant is specific to Europeans; it is not very common in East Asians. This gene has been found in other selection scans in Eurasian populations, but has never before been linked to Neandertal gene flow
I just received a review copy of E. O. Wilson’s The Social Conquest of Earth. One of the reasons why this book is “hot” is that Wilson has recently been revisiting the “levels of selection” debates, and significantly downgraded kin selection in the pantheon of evolutionary dynamics (at least in his mind). There has been a lot of talk on the blogs about Wilson’s ideas, in large part because of his partisan position on the Nowak vs. most other biologists debate, in favor of Nowak.
I don’t know if I’ll have time to review the book (a reality I honestly explained already to the people working at the publisher), but, it did get me thinking: what are the opinions of biologists in relation group selection? My personal experience is that opinions actually vary by discipline and by department. It’s hard to get a real sense, because people tend to be in their own “bubble.” With that in mind, I’ve put together a small survey to assess opinions. My core audience here are people who consider themselves biologists, though I can’t prevent someone with strong opinions from participating obviously!
The new article in The American Journal of Human Genetics, A “Copernican” Reassessment of the Human Mitochondrial DNA Tree from its Root, is open access, so you should check it out. The discussion gets to the heart of the matter:
Supported by a consensus of many colleagues and after a few years of hesitation, we have reached the conclusion that on the verge of the deep-sequencing revolution…when perhaps tens of thousands of additional complete mtDNA sequences are expected to be generated over the next few years, the principal change we suggest cannot be postponed any longer: an ancestral rather than a “phylogenetically peripheral” and modern mitogenome from Europe should serve as the epicenter of the human mtDNA reference system. Inevitably, the proposed change could raise some temporary inconveniences. For this reason, we provide tables and software to aid data transition.
What we propose is much more than a mere clerical change. We use the Ptolemaian geocentric versus Copernican heliocentric systems as a metaphor. And the metaphor extends further: as the acceptance of the heliocentric system circumvented epicycles in the orbits of planets, switching the mtDNA reference to an ancestral RSRS will end an academically inadmissible conjuncture where virtually all mitochondrial genome sequences are scored in part from derived-to-ancestral states and in part from ancestral-to-derived states. We aim to trigger the radical but necessary change in the way mtDNA mutations are reported relative to their ancestral versus derived status, thus establishing an intellectual cohesiveness with the current consensus of shared common ancestry of all contemporary human mitochondrial genomes.
Note that the problem is not restricted to mtDNA. Indeed, in the much larger perspective of complete nuclear genomes in which comparisons are often currently made relative to modern human reference sequences, often of European origin, it seems worthwhile to begin considering, as valuable alternatives, public reference sequences of ancestral alleles (common in all primates) whereby derived alleles (common to some human populations) would be distinguished.
Perhaps the first generation or so of human molecular evolutionary genetics might be thought of as a “first draft.” A serviceable first draft which rendered in broad strokes the gist of the truth as we understand it, but lacking in some essential details.
On a minor note, there are some theoretical reasons why mtDNA did not yield much evidence for archaic admixture, which is clear in the nuclear genomics (e.g., higher rate of change due to lower effective population size, so more rapid extinction of ancient lineages). But perhaps now that the number of complete mtDNA genomes is increasing in size we might start to see “long branches,” which reflect the inferences generated from the ancient nuclear genomes.
Dienekes and Maju have both commented on a new paper which looked at the likelihood of lactase persistence in Neolithic remains from Spain, but I thought I would comment on it as well. The paper is: Low prevalence of lactase persistence in Neolithic South-West Europe. The location is on the fringes of the modern Basque country, while the time frame is ~3000 BC. Table 3 shows the major result:
Lactase persistence is a dominant trait. That means any individual with at least one copy of the T allele is persistent. As Maju noted a peculiarity here is that the genotypes are not in Hardy-Weinberg Equilibrium. Specifically, there are an excess of homozygotes. Using the SJAPL location as a potentially random mating scenario you should expect ~7 T/C genotypes, not 2. Interestingly the persistent individual in the Longar location also a homozygote.