Tag: Evolutionary Genetics

The continuing tangling of the human tree

By Razib Khan | April 27, 2011 3:59 pm

ResearchBlogging.orgLast summer I made a thoughtless and silly error in relation to a model of human population history when asked by a reader the question: “which population is most distantly related to Africans?” I contended that all non-African populations are equally distant. This is obviously wrong on the face of it if you look at any genetic distance measures. West Eurasians, even those without recent Sub-Saharan African admixture (e.g., North Europeans) are closer than East Eurasians, who are often closer than Oceanians and Amerindians. One explanation I offered is that these latter groups were subject to greater genetic drift through a series of population bottlenecks. In this framework the number of generations until the last common ancestor with Sub-Saharan Africans for all groups outside of Africa should be about the same, but due to evolutionary factors such as more extreme genetic drift or different selective pressures some non-African groups had diverged more from Africans than others in terms of their genetic state. In other words, the most genetically divergent groups in relation to Africans did not diverge any earlier, but simply diverged more rapidly.

Dienekes Pontikos disagreed with such a simple explanation. He argued that admixture or gene flow between Africans and non-African groups since the last common ancestor could explain the differences. I am now of the opinion that Dienekes may have been right. My own confidence in the “serial bottleneck” hypothesis as the primary explanation for the nature of relationships of the phylogenetic tree of human populations is shaky at best. Why my errors of inference?

There were two major issues at work in my misjudgments of the arc of the past and the topology of the present. In the latter instance I saw plenty of phylogenetic trees which illustrated clearly the variation in genetic distance from Africans for various non-African groups. Why didn’t I internalize those visual representations? It was I think the power of the “Out of Africa” (OoA) with replacement paradigm. Even by the summer of 2010 I had come to reject it in its strong form, due to the evidence of admixture with Neanderthals, and rumors of other events which were born out to be true with the publishing of the Denisovan results. But to a first approximation the clean and simple OoA was still looming so large in my mind that I made the incorrect inference, whereby all non-Africans are viewed simply as a branch of Africans without any particular differentiation in relation to their ancestral population. Secondarily, I also was still impacted by the idea that most of the genetic variation you see in the world around us has its roots tens of thousands of years ago. By this, I mean that the phylogeographic patterns of 25,000 years in the past would map on well to the phylogeographic patterns of the present. This assumption is what drove a lot of phylogeography in the early aughts, because the chain of causation could be reversed, and inferences about the past were made from patterns of the present. My own confidence in this model had already been perturbed when I made my errors, but it still held some sort of sway in my head implicitly I believe. It is one thing to move on from old models explicitly, but another thing to remove the furniture from your cognitive basement and attic.

I have moved further from my preconceptions between then and now. It took a while to sink in, but I’m getting there. A cognitive “paradigm shift” if you will. In particular I am more open to the idea of substantive back migration to Africa, as well as secondary migrations out of Africa. A new paper in Genome Research is out which adds some interesting details to this bigger discussion, and seems to weigh in further against my tentative hypothesis that serial bottlenecks and genetic drift can explain variation in distance to Africans of various non-African groups. Human population dispersal “Out of Africa” estimated from linkage disequilibrium and allele frequencies of SNPs:

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The Court Jester and the averaging fallacy

By Razib Khan | April 21, 2011 2:39 am

The Pith:Climatic and biological evolutionary pressures on an ecosystem complement at different scales. Neither is “dominant,” as that framing is not even wrong.

Yesterday I alluded to the Court Jester hypothesis of evolutionary change, which is often contrasted with the Red Queen hypothesis. The main embarrassment for me as a person who fancies himself a fan of evolutionary process is that I hadn’t ever heard of the Court Jester Hypothesis before yesterday. Therefore I went back to the paper which outlined many of the basic ideas of the model in 2001, Distinguishing the effects of the Red queen and Court Jester on Miocene mammal evolution in the northern Rocky Mountains. To be fair, the hypothesis itself is a tightening of a range of ideas which were long in the air. I did know, for example, about the Turnover-pulse hypothesis. These are all a set of models which emphasize the abiotic selective pressures on life forms, as opposed to the biotic ones. An abiotic pressure would be something like the Younger Dryas cold snap. A biotic pressure might be an exotic invasive species spreading through the landscape.

In my own mind selection is selection, so I didn’t distinguish them too stridently. In fact, most people seem to have abiotic pressures in mind when they conceive of natural selection, so I generally prefer to emphasize the competition and cooperation between and within species. Additionally, it seems that biotic models are more formally tractable and elegantly constructed (I know much of climate change is cyclical, but I assume that “catastrophe” exhibits a poisson distribution?). I generally lack the “thick” knowledge to really make sense of a lot of detailed natural historical treatments, so I probably avoided them because I didn’t think I’d get much out of them. In hindsight, this seems foolish and shortsighted. Rather like economists focusing on equilibrium states because of their ease of modeling when periodic exogenous shocks are a major variable within our real lives.

ResearchBlogging.orgNow let’s hit the abstract:

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CATEGORIZED UNDER: Evolution, Genetics

Evolution in higher dimensions

By Razib Khan | April 18, 2011 12:22 am

Ornithomimosaurian dinosaur & ostrich, image credit Nobu Tamura & James G. Howes

ResearchBlogging.orgThe Pith: This post explores evolution at two different scales: the broad philosophical and the close in genetic. Philosophically, is evolution a highly contingent process which is not characterized by much replication of form and function? Or, is evolution at the end of the day aiming for a few set points which define the most optimal fitness positions possible? And how do both of these models relate to the interaction across genes, epistasis? In this post I review a paper which shows exactly how historical contingency could work through gene-gene interactions on the molecular genetic scale.

Imagine if you will a portal to another universe which you have access to. By fiat let’s give you a “pod” which allows you to move freely throughout this universe, and also let’s assume that you can travel fast enough to go from planet to planet. What if you see that on all the planets there’s a sludgy living “goo” of some sort? To complexify the issue imagine that upon further inspection the goo is divided between a predominant photosynthetic element, and “parasitic” heterotrophs. But aside from these two niches there’s little diversity to be seen in this cosmos. The “climax ecology” of all the planets resemble each other, in case after case convergent evolution toward the one-morphology-to-out-fit-them-all. We could from these observations construct a general theory of evolution which deemphasizes the role of contingency. In other words, there are broad general dynamics which shape and prune the tree of life in this hypothetical universe so that there is always a final terminal steady-state of the most fit morphology.

A model of evolution as a process of very general principles which converges upon a small finite range of optimal solutions has been promoted by paleontologists such as Simon Conway Morris. Stephen Jay Gould was a famous expositor of the inverse position, which emphasized chance and contingency. Gould’s suggestion was that if you ran the evolutionary experiment anew the outcomes each time would likely differ. In The Ancestor’s Tale Richard Dawkins leans toward the former position, insofar as he does assent to the proposition that evolutionary dynamics do inevitably forward certain broad trends, irrespective of the specific historical sequence of states antecedent to the terminus. More fanciful and speculative extrapolations of this logic are used to justify the ubiquity of a humanoid morphology in science fiction. The theory goes that a bipedal organism whose upper limbs are free to manipulate tools is going to be the likely body plan of intelligent aliens (though they will also have easy to add nose frills and such).

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CATEGORIZED UNDER: Evolution, Genetics

Evolution may explain why baby comes early

By Razib Khan | April 16, 2011 5:36 pm

Image credit

The Pith: In this post I review a paper which covers the evolutionary dimension of human childbirth. Specifically, the traits and tendencies peculiar to our species, the genes which may underpin those traits and tendencies, and how that may relate to broader public health considerations.

Human babies are special. Unlike the offspring of organisms such as lizards or snakes human babies are exceedingly helpless, and exhibit an incredible amount of neoteny in relation to adults. This is true to some extent for all mammals, but obviously there’s still a difference between a newborn foal and a newborn human. One presumes that the closest analogs to human babies are those of our closest relatives, the “Great Apes.” And certainly the young of chimpanzees exhibit the same element of “cuteness” which is appealing to human adults. Still there is a difference of degree here. As a childophobic friend observed human infants resemble “larvae.” The ultimate and proximate reason for this relative underdevelopment of human newborns is usually attributed to our huge brains, which run up against the limiting factor of the pelvic opening of women. If a human baby developed for much longer through extended gestation then the mortality rates of their mothers during childbirth would rise. Therefore natural selection operated in the direction it could: shortening gestation times. You might say that in some ways then the human newborn is an extra-uterine fetus.

ResearchBlogging.orgA new paper in PLoS Genetics attempts to fix upon which specific genomic regions might be responsible for this accelerated human gestational clock. An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing:

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The flat and the fit

By Razib Khan | March 29, 2011 2:10 am

ResearchBlogging.orgThe Pith: In evolution if you want to win in the long run you don’t want all your eggs in one basket, even if that’s the choicest basket. Sh*t happens, and you better have some back up strategies.

Diversity is a major question in evolutionary biology. In particular, why is there so much diversity, so that the tree of life manifests a multitude of morphs? Might there not be some supreme replicator which emerges from the maelstrom to conquer all before it? This is actually the scenario which unfolds in much of science fiction, with monomorphic grey goo eating everything in its path (a more aesthetically differentiated variant of the super-species emerges in Brian W. Aldiss’  Helliconia Winter). As it is, life on earth does not seem to be converging upon an optimum phenotype for all individuals. In contrast, it seems to be going in the opposite direction broadly speaking (thinking on billion year scales), with the shift from the monotony of communal cyanobacteria to the riotous diversity of tropical forest biomes and coral reefs.

There are many ways you might be able to explain this diversity. Temporal and spatial heterogeneity produces perpetually shifting selection pressures, resulting in transient morphs one after the other. Negative frequency dependent selection, whereby the fitness of a phenotype runs up against its own success. This dynamic is one of the drivers of the Red Queen Hypothesis; the evolutionary arms race in some cases witnessing the resurrection of old techniques against which defenses are no longer recalled. Then there is the possibility that the lack of natural selection as an efficacious evolutionary force could allow for the diversification of phenotypes through  random drift. Finally, it may simply be that the gusher of mutation is powerful enough that novelty overwhelms selection and drift’s attempt to pare it back.

A new paper in Nature offers up another possibility. It does so by examining the fact that biological diversity remains operative even within a homogenized chemostat. A chemostat in this context refers to a controlled environment where inputs and outputs are balanced to maintain constant equilibrium conditions for a bacterialculture. Therefore, an unbeatable strategy should emerge in this medium perfectly tailored to the environmental constants, resulting in a homogeneous biota to match. Empirically this is not what occurs. So some explanation is warranted.

Metabolic trade-offs and the maintenance of the fittest and the flattest:

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Sweeping through a fly's genome

By Razib Khan | February 23, 2011 2:44 pm

Credit: Karl Magnacca

The Pith: In this post I review some findings of patterns of natural selection within the Drosophila fruit fly genome. I relate them to very similar findings, though in the opposite direction, in human genomics. Different forms of natural selection and their impact on the structure of the genome are also spotlighted on the course of the review. In particular how specific methods to detect adaptation on the genomic level may be biased by assumptions of classical evolutionary genetic models are explored. Finally, I try and place these details in the broader framework of how best to understand evolutionary process in the “big picture.”

A few days ago I titled a post “The evolution of man is no cartoon”. The reason I titled it such is that as the methods become more refined and our data sets more robust it seems that previously held models of how humans evolved, and evolution’s impact on our genomes, are being refined. Evolutionary genetics at its most elegantly spare can be reduced down to several general parameters. Drift, selection, migration, etc. Exogenous phenomena such as the flux in census size, or environmental variation, has a straightforward relationship to these parameters. But, to some extent the broadest truths are nearly trivial. Down to the brass tacks what are these general assertions telling us? We don’t know yet. We’re in a time of transitions, though not troubles.

ResearchBlogging.orgGoing back to cartoons, starting around 1970 there were a series of debates which hinged around the role of deterministic adaptive forces and random neutral ones in the domain of evolutionary process. You have probably heard terms like “adaptationist,” “ultra-Darwinian,” and “evolution by jerks” thrown around. All great fun, and certainly ripe “hooks” to draw the public in, but ultimately that phase in the scientific discourse seems to have been besides the point. A transient between the age of Theory when there was too little of the empirics, and now the age of Data, when there is too little theory. Biology is a very contingent discipline, and it may be that questions of the power of selection or the relevance of neutral forces will loom large or small dependent upon the particular tip of the tree of life to which the question is being addressed. Evolution may not be a unitary oracle, but rather a cacophony from which we have to construct a harmonious symphony for our own mental sanity. Nature is one, an the joints which we carve out of nature’s wholeness are for our own benefit.

The age of molecular evolution, ushered in by the work on allozymes in the 1960s, was just a preface to the age of genomics. If Stephen Jay Gould and Richard Dawkins were in their prime today I wonder if the complexities of the issues on hand would be too much even for their verbal fluency in terms of formulating a concise quip with which to skewer one’s intellectual antagonists. Complexity does not make fodder for honest quips and barbs. You’re just as liable to inflict a wound upon your own side through clumsiness of rhetoric in the thicket of the data, which fires in all directions.

In any case, on this weblog I may focus on human genomics, but obviously there are other organisms in the cosmos. Because of the nature of scientific funding for reasons of biomedical application humans have now come to the fore, but there is still utility in surveying the full taxonomic landscape. As it happens a paper in PLos Genetics, which I noticed last week, is a perfect complement to the recent work on human selective sweeps. Pervasive Adaptive Protein Evolution Apparent in Diversity Patterns around Amino Acid Substitutions in Drosophila simulans:

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CATEGORIZED UNDER: Evolution, Genetics, Genomics

The evolution of man is no cartoon

By Razib Khan | February 22, 2011 1:45 am

ResearchBlogging.orgI was semi-offline for much of last week, so I only randomly heard from someone about the “Science paper” on which Molly Przeworski is an author. Finally having a chance to read it front to back it seems rather a complement to other papers, addressed to both man and beast. The major “value add” seems to be the extra juice they squeezed out of the data because they looked at the full genomes, instead of just genotypes. As I occasionally note the chips are marvels of technology, but the markers which they are geared to detect are tuned to the polymorphisms of Europeans.

Classic Selective Sweeps Were Rare in Recent Human Evolution:

Efforts to identify the genetic basis of human adaptations from polymorphism data have sought footprints of “classic selective sweeps” (in which a beneficial mutation arises and rapidly fixes in the population). Yet it remains unknown whether this form of natural selection was common in our evolution. We examined the evidence for classic sweeps in resequencing data from 179 human genomes. As expected under a recurrent-sweep model, we found that diversity levels decrease near exons and conserved noncoding regions. In contrast to expectation, however, the trough in diversity around human-specific amino acid substitutions is no more pronounced than around synonymous substitutions. Moreover, relative to the genome background, amino acid and putative regulatory sites are not significantly enriched in alleles that are highly differentiated between populations. These findings indicate that classic sweeps were not a dominant mode of human adaptation over the past ~250,000 years.

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CATEGORIZED UNDER: Genetics, Genomics

More bad mutations = greater fitness

By Razib Khan | January 13, 2011 1:58 am

ResearchBlogging.orgDoes the chart above strike you as strange? What it shows is that the mean fitness of a population drops as you increase the rate of deleterious mutation (many more mutations are deleterious than favorable)…but at some point the fitness of the population bounces back, despite (or perhaps because of?) the deleterious mutations! This would seem, to me, an illustration of bizzaro-world evolution. Worse is better! More is less! Deleterious is favorable? By definition deleterious isn’t favorable, so one would have to back up and check one’s premises.

And yet this seems just what a new paper in PLoS ONE is reporting. Purging Deleterious Mutations under Self Fertilization: Paradoxical Recovery in Fitness with Increasing Mutation Rate in Caenorhabditis elegans:

Compensatory mutations can be more frequent under high mutation rates and may alleviate a portion of the fitness lost due to the accumulation of deleterious mutations through epistatic interactions with deleterious mutations. The prolonged maintenance of tightly linked compensatory and deleterious mutations facilitated by self-fertilization may be responsible for the fitness increase as linkage disequilibrium between the compensatory and deleterious mutations preserves their epistatic interaction.

Got that? OK, you probably need some background first….

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CATEGORIZED UNDER: Evolution, Genetics, Genomics

Sex with thee and the last woman

By Razib Khan | October 18, 2010 2:03 am

Male_and_female_pheasantA quintessentially sexy topic in biology is the origin of sex. Not only are biologists interested in it, but so is the public. Of Matt Ridley’s older books it is predictable that The Red Queen has the highest rank on Amazon. We humans have a fixation on sex, both in our public norms and our private actions. Why?

Because without a fixation on sex we would not be here. Celibates do not inherit the earth biologically. This answer emerges naturally from a Darwinian framework. And yet more deeply still: why sex for reproduction? Here I allude to the famous two-fold cost of sex. In dioecious species you have males and females, and males do not directly produce offspring. The increase of the population is constrained by the number of females in such lineages (male gametes are cheap). There is no such limitation in asexual lineages, where every individual can contribute to reproductive “primary production.” Additionally, the mating dance is another cost of sex. Individuals expend time and energy seeking out mates, and may have to compete and display for the attention of all. Why bother?

ResearchBlogging.orgThe answer on the broadest-scale seems to be variation. Variation in selective pressures, and variation in genes. Sex famously results in the shuffling of genetic permutations through recombination and segregation. In a world of protean change where one’s genes are critical to giving one the edge of fitness this constant flux of combinations results in more long term robusticity. What clones gain in proximate perfection, they lose when judged by the vicissitudes of the pressures of adaptation. In the present they flourish, but in the future they perish. Sex is the tortoise, clonal reproduction is the hare.

And yet science is more than just coarse generalities; biology especially so. The details of how sex emerges ad persists still remains to be fleshed out. The second volume of W. D. Hamilton’s collected papers, Narrow Roads of Gene Land, is the largest. Mostly because it was not edited appropriately (he died before it could be). But also perhaps because it is the volume most fixated upon the origin and persistence of sex, which is a broad and expansive topic.

A new paper in Nature tackles sex through experimental evolution. In may ways the answer it offers to the question of sex is old-fashioned and straightforward. Higher rates of sex evolve in spatially heterogeneous environments:

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CATEGORIZED UNDER: Evolution, Genetics

The adaptive space of complexity

By Razib Khan | October 4, 2010 3:55 pm

evocomplexEvolution means many things to many people. On the one hand some scholars focus on time scales of “billions and billions,” and can ruminate upon the radical variation in body plans across the tree of life. Others put the spotlight on the change in gene frequencies on the scale of years, of Ph.D. programs. While one group must glean insight from the fossil remains of trilobites and ammonites, others toils away in dimly lit laboratories breeding nematodes and fruit flies, generations upon generations. More recently a new domain of study has been focusing specifically on the arc of animal development as a window onto the process of evolution. And so forth. Evolution has long been dissected by an army of many specialized parts.

ResearchBlogging.orgAnd yet the core truth which binds science is that nature is one. No matter the disciplinary lens which we put on at any given moment we’re plumbing the same depths on some fundamental level. But what are the abstract structures of those depths? Can we project a tentative map of the fundamentals before we go exploring through observation and experiment? That’s the role of theoreticians. Charles Darwin, R. A. Fisher, and Sewall Wright. Evolution is a phenomenon which is on a deep level an abstraction, though through objectification we speak of it as if it was as concrete as the frills of the Triceratops. As an abstraction it is open to mathematical formalization. Models of evolution may purport to tell us how change over time occurs in specific instances, but the ultimate aim is to capture the maximum level of generality possible.

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CATEGORIZED UNDER: Evolution, Genetics, Genomics

Story of X

By Razib Khan | September 27, 2010 12:35 am

A month ago I pointed to a short communication in Nature Genetics which highlighted differences in the patterns of variation between the X chromosome and the autosome. I thought it would be of interest to revisit this, because it’s a relatively short piece with precise and crisp results which we can ruminate upon.

ResearchBlogging.orgSometimes there is a disjunction between how evolutionary biologists and molecular biologists use terms like “gene.” The issue is explored in depth in Andrew Brown’s The Darwin Wars. Brown observes that one of the problems with Richard Dawkins’ style of exposition is that it did not translate well to the American context. He spoke of genes as units of analysis, from which logical inferences could be made. This was the classical Oxford style of evolutionary biology which Ernst Mayr objected to. In contrast American biologists were used to thinking of genes in more concrete biophysical terms, and tended to miss the theoretical context which Dawkins was alluding to in his arguments. In Dawkins’ defense, it must be remembered that the gene does have its origins as an abstract entity whose biophysical substrate, DNA, was not known for decades. In my post Simple rules for inclusive fitness I outlined a paper which is very much in keeping with the analytic tradition. Start with an abstract model and allow the chain of inferences to be made, and see where it takes you.

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CATEGORIZED UNDER: Biology, Genetics, Genomics

Raging against the population genetics machine

By Razib Khan | September 20, 2010 5:32 pm

An interesting readable review in PLoS Genetics taking on population genetics, Frail Hypotheses in Evolutionary Biology:

In conclusion, I return to Michael Lynch’s challenging questions about blind spots and bad wheels in evolutionary biology which motivated this review…Concerning blind spots I have pointed out some limitations of current population genetics. There is too much emphasis on elegant mathematics, and not enough concern for the real values of the critical parameters -in particular, in models of mutation spread and fixation, or in models of optimal mutation rates. Recombination, a crucial genetic mechanism, is misrepresented in the models. Features that looked anecdotal, such as recombination between sister chromatids and germ-line mutations are perhaps central to the mechanisms of evolution in higher organisms. My proposals on mutation strategies…—see also Amos…—lead to rather precise insights on compensatory mutations or polymorphism propagation, yet they are largely ignored by population geneticists.

The beauty of population genetics is that it leads to relatively simple algebras which one can use to guide one’s intuitions. Phenomena such as selection or drift are more than words, they’re specific values. That being said, plenty of readers of this weblog have expressed caution, and skepticism, at the over-utilization of monogenic diallelic models as “quick & dirty” prototypes for evolution more generally. More concretely small changes in parameter values can lead to radically different inferences within the real context of natural history. Excessive reliance on elegant population genetic theory can lead one astray just as excessive reliance on economic theory can. The real world introduces so many complications that discarding too many of them to make a model tractable may render the framework of trivial importance, or even lead one down false paths. I don’t find author’s specific objections of distinction, but the paper is useful as an entry-point into the debate within the literature. The fact that R. A. Fisher, J. B. S. Haldane, and Sewall Wright, did not predict the full path of empirical discovery over the 20th century indicates very concretely the limitations of theoretical frameworks within biology.

CATEGORIZED UNDER: Genetics, Genomics

A fly's life: adventures in experimental evolution

By Razib Khan | September 16, 2010 3:15 am

509px-Drosophila_residua_heNatural selection happens. It was hypothesized in copious detail by Charles Darwin, and has been confirmed in the laboratory, through observation, and also by inference via the methods of modern genomics. But science is more than broad brushes. We need to drill-down to a more fine-grained level to understand the dynamics with precision and detail, and so generate novel inferences which may then be tested. For example, there are various flavors of natural selection: stabilizing selection, negative selection, and positive directional selection. In the first case natural selection buffets the phenotype about an ideal mean, in the second case deleterious phenotypes and their associated alleles are purged from the genome, and finally, natural selection can also drive a novel trait toward greater prominence, and concomitantly the allelic variants which are associated with the fitter phenotype.

The last case is of particular interest to many because it is often with positive natural selection by which evolution as descent with modification occurs. Over time trait values and the nature of traits themselves shift such that a lineage changes its character beyond recognition. This phyletic gradualism and the scale independence of evolutionary process has been challenged, in particular from the domain of developmental biology (albeit, not all ,or even most, developmental biologists). But ultimately no one doubts that a classical understanding of evolution as change in allele frequency, often driven by natural selection, is part of the larger puzzle of how the tree of life came to be.

ResearchBlogging.orgOne of the phenomena associated with positive directional evolution is the selective sweep. How a selective sweep occurs, and its consequences, are rather straightforward. A genome consists of a sequence of base pairs (e.g., we have 3 billion base pairs). If a new mutation emerges at a particular base pair, a novel single nucelotide polymorphism (SNP), and, that allelic variant is ~10% fitter than the ancestral variant, natural selection could drive up its frequency (the conditionality is due to the fact that in all likelihood it would still go extinct because of the power of stochastic forces when a mutant is at low frequency). So the variant could in theory shift from ~0% (1 out of N, N being the number of individuals in a population, 2N if diploid, and so forth) to ~100%. This would be the fixation of the novel variant, driven by selective dynamics. So what’s the sweep aspect? The sweep in this case refers to the effect of the very rapid rise in frequency of the SNP in question on the adjacent genomic region. What is termed a genetic hitchiking dynamic results if the sweep occurs rapidly, so that nearby regions of the genome also move to fixation along with the favored SNP. But in a diploid organism with sexual reproduction genetic recombination persistently breaks apart associations across the physical genome. Therefore the span of the sequence of genetic markers nearby a favored SNP which form a haplotype is dependent on the rate of recombination as well as the rate of the rise in frequency of the allele, which is contingent on the strength of selection. A powerful selective sweep has the effect of homogenizing wide regions of the genome flanking the favored mutant; in other words the sweep “cleans” the gene pool of variation as one very long haplotype replaces many shorter haplotypes. As an example, in the genomes of Northern Europeans the locus LCT is characterized by a very long haplotype, which itself seems to correlate well with the trait of lactase persistence. The implication here is that the lactase persistence conferring variant arose relatively recently, and was swept up to near fixation by positive directional natural selection.

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CATEGORIZED UNDER: Evolution, Genetics, Genomics

Sexual selection: lowered expectations edition

By Razib Khan | September 8, 2010 3:45 am

800px-Pfau_imponierendSexual selection is, for lack of a better term, a sexy concept. Charles Darwin elaborated on the specific phenomenon of sexual selection in The Descent of Man, and Selection in Relation to Sex. In The Third Chimpanzee Jared Diamond endorsed Darwin’s thesis that sexual selection could explain the origin of human races, as each isolated population extended their own particular aesthetic preferences. More recently the evolutionary psychologist Geoffrey Miller put forward an entertaining, if speculative, battery of arguments in The Mating Mind: How Sexual Choice Shaped the Evolution of Human Nature. It’s clearly the stuff of science that can sell.

Sexual selection itself comes in a variety of flavors. Perhaps the most counterintuitive one on first blush is the idea that many traits, such as antlers, are positively costly and exist only to signal robust health which can incur the cost without debility. The idea was outlined by Amotz Zahavi in The Handicap Principle in the 1970s. Initially dismissed by Richard Dawkins in the original edition of The Selfish Gene, Zahavi’s ideas have come into modest mainstream acceptance, and the second edition of Dawkins’ seminal work reflects a revised appraisal. This is really a subset of a “good genes” model of sexual selection, whereby females select from a range of males which would exhibit variance in mutational load. A more capricious and erratic form of sexual selection is “runaway,” which like genetic drift needs no rhyme or reason. Rather, arbitrary initial preferences can become coupled with heritable preference in a positive feedback loop which drives the mean phenotypic value of a population off the previous median, until natural selection enforces a countervailing pressure once the trait starts to become excessively maladaptive (e.g., imagine selection for longer and longer tail feathers until the ability of a bird to fly is inhibited).

ResearchBlogging.orgPaul_Giamatti_2008But notwithstanding the inevitable press which the theory gets, and its centrality to several popular science books, the main action in the area of sexual selection is in the academic literature (contrast this with the aquatic ape hypothesis). Many of the verbal outlines of sexual selection are highly stylized, as economists might say. We are treated to images of stags with massive antlers facing off, elephant seals strutting their stuff, and beautifully plumaged birds gathering for a lek. Set next to this is a body of mathematically oriented models, short on color, long on Greek symbols.  But these formal models are valuable. Obviously there is a wide range of variation across species in terms of how sexual selection plays out (if it does so at all within a given species, sexual or asexual). The sexual dimorphism of elephant seals is not the norm against which all species are judged. To explore the variables which produce this pattern of difference one must analyze them in an algebraic fashion, where each can be manipulated in isolation so as to properly characterize its impact. So with that, a paper from The American Naturalist which purports to show how assortative mating could emerge in a sexual selective framework, Make love not war: when should less competitive males choose low-quality but defendable females?:

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CATEGORIZED UNDER: Evolution, Genetics, Select

HapMap 3: more people ~ more genetic variation

By Razib Khan | September 1, 2010 3:28 pm

Across the ~3 billion or so base pairs in the human genome there’s a fair amount of variation. That variation can be partitioned into different classes, somewhat artificial constructions of human categorization systems, but nevertheless mapping on to real demographic or life history events of particular importance. Some of the variation is specific to populations, while some of it is specific to a set of populations, and, there is also variation which we find only within families. Presumably when whole genome sequencing and analysis becomes the norm such distinctions will still have utility, but we should be able to tunnel down to whatever level of analysis we wish. But until that day comes we’re going to have to rely on population sets which are deeply sequenced and can serve as a reasonable representation of a subset of human variation.

ResearchBlogging.orgI mention some of these populations regularly on this weblog, the HGDP, HapMap and POPRES being three prominent data sets with a diverse range. These groups cover only a small subset of human populations, and of those populations only a small proportion of the genomes of individuals (albeit, the component which is likely to vary within the population). A new paper in Nature takes a close look at the expansion of the HapMap to a new set of populations. Since it’s out of the HapMap consortium the list of authors themselves gives us a large set of individuals who might be of population genetic interest! (though not a representative set of human population variation; where are the Papuan employees of the Broad Institute?) Some of the data coming out of the next stage of the HapMap has been found in several papers already (often in the supplements), but this looks to be an overview and taste of what’s to come (the paper was submitted last fall). Integrating common and rare genetic variation in diverse human populations:

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CATEGORIZED UNDER: Evolution, Genetics, Genomics, Select

Not the origin of genome complexity

By Razib Khan | August 27, 2010 12:50 pm

ResearchBlogging.orgOver the past decade evolutionary geneticist Mike Lynch has been articulating a model of genome complexity which relies on stochastic factors as the primary motive force by which genome size increases. The argument is articulated in a 2003 paper, and further elaborated in his book The Origins of Genome Architecture. There are several moving parts in the thesis, some of which require a rather fine-grained understanding of the biophysical structural complexity of the genome, the nature of Mendelian inheritance as a process, and finally, population genetics. But the core of the model is simple: there is an inverse relationship between long term effective population size and genome complexity. Low individual numbers ~ large values in terms of base pairs and counts of genetic elements such as introns.

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CATEGORIZED UNDER: Evolution, Genetics, Genomics

A thousand little adaptive platoons

By Razib Khan | August 23, 2010 4:40 am

adaptive_landscape_labelledLast week I took an intellectual road trip back nearly a century and explored the historical context and scientific logic by which R. A. Fisher definitively fused Mendelian genetics with quantitative evolutionary biology. In the process he helped birth the field of population genetics. While the genetics which we today are more familiar with begins at the biophysical substrate, the DNA molecule, and the phenomena which emerge from its concrete structure, population genetics starts with the abstract concept of the gene. This abstraction and its variants are construed as algebraic quantities from which one can infer a host of dynamics. These are the processes which are the foundations of evolutionary change, as population genetics flows into evolutionary genetics, and ultimately the raw material of natural history.

ResearchBlogging.orgFisher’s accomplishments were a function of both his abilities and his passions. He was a mathematical prodigy, with the ability to distill natural processes down to highly general abstractions. And like many English gentlemen of his age he had a passion for evolutionary biology, and cherished his copy of The Origin Of Species. His ultimate aim was to transform evolutionary biology into a discipline with the same analytical rigor as physical chemistry. But he wasn’t the only major figure on the scene in his era.

Sewall_WrightSewall Wright was an American physiological geneticist with a background in animal breeding. While Fisher was a mathematician who sought to apply his skills to evolutionary biology, Wright was a biologist who taught himself mathematics to further his own understanding of evolutionary processes. The two were in many ways the Yin and the Yang of early population genetics, with their conflicts and disagreements being termed the Wright-Fisher controversies, and the common formal framework which they converged upon becoming the ubiquitous Wright-Fisher model. Wright’s life spanned 99 years, from 1889 to 1988. His biography, both personal and scientific, are explored in rich detail in Will Provine’s Sewall Wright and Evolutionary Biology. Because of the length and breadth of his influence in evolution it’s worth reading just to get a sense of how Wright shaped the Modern Neo-Darwinian Synthesis behind the scenes. Provine seems to indicate that Wright was the primary theoretical influence on Theodosius Dobzhansky,* who mentored a whole generation of evolutionary biologists to come (e.g., Dobzhansky → Lewontin → Coyne).

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CATEGORIZED UNDER: Evolution, Genetics

Genetics is One: Mendelism and quantitative traits

By Razib Khan | August 17, 2010 6:31 am


ResearchBlogging.orgIn the early 20th century there was a rather strange (in hindsight) debate between two groups of biological scientists attempting to understand the basis of inheritance and its relationship to evolutionary processes. The two factions were the biometricians and Mendelians. As indicated by their appellation the Mendelians were partisans of the model of inheritance formulated by Gregor Mendel. Like Mendel many of these individuals were experimentalists, with a rough & ready qualitative understanding of biological processes. William Bateson was arguably the model’s most vociferous promoter. Set against the Mendelians were more mathematically minded thinkers who viewed themselves as the true inheritors of the mantle of Charles Darwin. Though the grand old patron of the biometricians was Francis Galton, the greatest expositor of the school was Karl Pearson.* Pearson, along with the zoologist W. F. R. Weldon, defended Charles Darwin’s conception of evolution by natural selection during the darkest days of what Peter J. Bowler terms “The Eclipse of Darwinism”.** One aspect of Darwin’s theory as laid out in The Origin of Species was gradual change through the operation of natural selection upon extant genetic variation. There was a major problem with the model which Darwin proposed: he could offer no plausible engine in regards to mode of inheritance. Like many of his peers Charles Darwin implicitly assumed a blending model of inheritance, so that the offspring would be an analog constructed about the mean of the parental values. But as any old school boy knows the act of blending diminishes variation! This, along with other concerns, resulted in a general tendency in the late 19th century to accept the brilliance of the idea of evolution as descent with modification, but dismiss the motive engine which Charles Darwin proposed, gradual adaptation via natural selection upon heritable variation.

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CATEGORIZED UNDER: Evolution, Genetics

Doing evolution's sums

By Razib Khan | May 27, 2010 4:10 pm

PLoS Biology has a review of Elements of Evolutionary Genetics up, Evolution Is a Quantitative Science:

But why has evolutionary genetics stood apart from biology’s resolutely qualitative, rather than quantitative, tradition? Most remarkably, while biomechanics employs the laws of physics, and biochemistry is founded on the quantitative science of chemistry, evolutionary genetics is based on axiomatic foundations that are entirely biological, and yet are capable of precise mathematical formulation. The rules of Mendelian genetics, encapsulated by unbiased inheritance and random mating in a diploid genetic system, predict Hardy-Weinberg frequencies, the binomial sampling of gametes in finite populations determines the properties of genetic drift, and, with a Poisson process of mutation, the complex theory of neutral genetic variation can be established on the basis of very simple assumptions.

A few books to get a historical perspective of the origins of modern evolutionary genetics (albeit with a pop gen focus), The Origins of Theoretical Population Genetics, Sewall Wright and Evolutionary Biology and R.A. Fisher: The Life of a Scientist.


When a trait isn't a trait isn't a trait

By Razib Khan | April 12, 2010 6:15 am

ResearchBlogging.orgOne of the great things about evolutionary theory is that it is a formal abstraction of specific concrete aspects of reality and dynamics. It allows us to squeeze inferential juice from incomplete prior knowledge of the state of nature. In other words, you can make predictions and models instead of having to observe every last detail of the natural world. But abstractions, models and formalisms often leave out extraneous details. Sometimes those details turn out not to be so extraneous. Charles Darwin’s original theory of evolution had no coherent or plausible mechanism of inheritance. R. A. Fisher and others imported the empirical reality of Mendelism into the logic of evolutionary theory, to produce the framework of 20th century population genetics. Though accepting the genetic inheritance process of Mendelism this is original synthesis was not informed by molecular biology, because it pre-dated molecular biology. After James Watson and Francis Crick uncovered the biophysical basis for Mendelism molecular evolution came to the fore, and neutral theory emerged as a response to the particular patterns of genetic variation which new molecular techniques were uncovering. And yet through this much of R. A. Fisher’s image of an abstract genetic variant floating against a statistical soup of background noise variation persisted, sometimes dismissed as “bean bag genetics”.

We’ve come a long way from the first initial wave of discussions which were prompted by the molecular genetic revolution. We have epigenetics, evo-devo and variation in gene regulation. None of these processes “overthrow” evolutionary biology, though in some ways they may revolutionize aspects of it. Science is over the long haul after all an eternal revolution, as the boundaries of comprehension keep getting pushed outward. A few days ago I pointed to Sean Carroll’s recent work, which emphasizes that one must think beyond the sequence level, and focus on particular features such as cis-regulartory elements. Here we’ve been tunneling down to the level of the gene, but what about the traits, the phenotypes, which are affected by genetic variation?

It is well known that the sparest abstraction of genotypic-phenotypic relationship can be illustrated like so:

genetic variation → phenetic variation

But each element of this relation has to be examined greater detail. What type of genetic variation? Sequence level variation? Epigenetic variation? The second component is perhaps the most fraught, with the arrow waving away the myriad details and interactions which no doubt lurk between genotype and phenotype. And finally you have the phenotype itself. Are they all created alike in quality so that we can ascribe to them dichotomous values and quantities?

A new paper in PNAS examines the particulars of morphological phenotypes and physiological phenotypes, and their genetic control, as well as rates of evolution. Contrasting genetic paths to morphological and physiological evolution:
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CATEGORIZED UNDER: Evolution, Genetics, Genomics, Science

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