There is the fact of evolution. And then there is the long-standing debate of how it proceeds. The former is a settled question with little intellectual juice left. The latter is the focus of evolutionary genetics, and evolutionary biology more broadly. The debate is an old one, and goes as far back as the 19th century, where you had arch-selectionists such as Alfred Russel Wallace (see A Reason For Everything) square off against pretty much the whole of the scholarly world (e.g., Thomas Henry Huxely, “Darwin’s Bulldog,” was less than convinced of the power of natural selection as the driving force of evolutionary change). This old disagreement planted the seeds for much more vociferous disputations in the wake of the fusion of evolutionary biology and genetics in the early 20th century. They range from the Wright-Fisher controversies of the early years of evolutionary genetics, to the neutralist vs. selectionist debate of the 1970s (which left bad feelings in some cases). A cartoon-view of the implication of the debates in regards to the power of selection as opposed to stochastic contingency can be found in the works of Stephen Jay Gould (see The Structure of Evolutionary Theory) and Richard Dawkins (see The Ancestor’s Tale): does evolution result in an infinitely creative assortment due to chance events, or does it drive toward a finite set of idealized forms which populate the possible parameter space?*
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):
Long time readers will be familiar with the large literature in behavior genetics/genomics and dopamine receptor genes. So with that, I point you to a paper exploring the patterns of variation and their relationship to possible natural selection, No Evidence for Strong Recent Positive Selection Favoring the 7 Repeat Allele of VNTR in the DRD4 Gene:
The human dopamine receptor D4 (DRD4) gene contains a 48-bp variable number of tandem repeat (VNTR) in exon 3, encoding the third intracellular loop of this dopamine receptor. The DRD4 7R allele, which seems to have a single origin, is commonly observed in various human populations and the nucleotide diversity of the DRD4 7R haplotype at the DRD4 locus is reduced compared to the most common DRD4 4R haplotype. Based on these observations, previous studies have hypothesized that positive selection has acted on the DRD4 7R allele. However, the degrees of linkage disequilibrium (LD) of the DRD4 7R allele with single nucleotide polymorphisms (SNPs) outside the DRD4 locus have not been evaluated. In this study, to re-examine the possibility of recent positive selection favoring the DRD4 7R allele, we genotyped HapMap subjects for DRD4 VNTR, and conducted several neutrality tests including long range haplotype test and iHS test based on the extended haplotype homozygosity. Our results indicated that LD of the DRD4 7R allele was not extended compared to SNP alleles with the similar frequency. Thus, we conclude that the DRD4 7R allele has not been subjected to strong recent positive selection.
In that vein, I also stumbled upon this paper recently, Contrasting signals of positive selection in genes involved in human skin-color variation from tests based on SNP scans and resequencing:
The Pith: What makes rice nice in one varietal may not make it nice in another. Genetically that is….
Rice is edible and has high yields thanks to evolution. Specifically, the artificial selection processes which lead to domestication. The “genetically modified organisms” of yore! The details of this process have long been of interest to agricultural scientists because of possible implications for the production of the major crop which feeds the world. And just as much of Charles Darwin’s original insights derived from his detailed knowledge of breeding of domesticates in Victorian England, so evolutionary biologists can learn something about the general process through the repeated instantiations which occurred during domestication during the Neolithic era.
A new paper in PLoS ONE puts the spotlight on the domestication of rice, and specifically the connection between particular traits which are the hallmark of domestication and regions of the genome on chromosome 3. These are obviously two different domains, the study and analysis of the variety of traits across rice strains, and the patterns in the genome of an organism. But they are nicely spanned by classical genetic techniques such as linkage mapping which can adduce regions of the genome of possible interesting in controlling variations in the phenotype.
In this paper the authors used the guidelines of the older techniques to fix upon regions which might warrant further investigation, and then applied the new genomic techniques. Today we can now gain a more detailed sequence level picture of the genetic substrate which was only perceived at a remove in the past through abstractions such as the ‘genetic map.’ Levels and Patterns of Nucleotide Variation in Domestication QTL Regions on Rice Chromosome 3 Suggest Lineage-Specific Selection:
Last week I reviewed ideas about the effect of “exogenous shocks” to an ecosystem of creatures, and how it might reshape their evolutionary trajectory. These sorts of issues are well known in their generality. They have implications from the broadest macroscale systematics to microevolutionary process. The shocks point to changes over time which have a general effect, but what about exogenous parameters which shift spatially and regularly? I’m talking latitudes here. The further you get from the equator the more the climate varies over the season, and the lower the mean temperature, and, the less the aggregate radiation the biosphere catches. Allen’s rule and Bergmann’s rule are two observational trends which biologists have long observed in relation to many organisms. The equatorial variants are slimmer in their physique, while the polar ones are stockier. Additionally, there tends to be an increase in mean mass as one moves away from the equator.
But these rules are just general observations. What process underlies these observations? The likely culprit would be natural selection of course. But the specific manner in which this process shakes out, on both the organismic and genetic level, still needs to be elucidated in further detail. A new paper in PLoS Genetics attempts to do this more rigorously and deeply than has been done before for one particular world wide mammalian species, H. sapiens sapiens. We have spanned the latitudes and longitudes, and so we’re a perfect test case for an exploration of the broader microevolutionary forces which shape variation.
The paper is Adaptations to Climate-Mediated Selective Pressures in Humans. Its technical guts can be intimidating, but its initial questions and final answers are less daunting. So let’s jump straight to the last paragraph of the discussion:
Last month in Nature Reviews Genetics there was a paper, Measuring selection in contemporary human populations, which reviewed data from various surveys in an attempt to adduce the current trajectory of human evolution. The review didn’t find anything revolutionary, but it was interesting to see where we’re at. If you read this weblog you probably accept a priori that it’s highly unlikely that evolution “has stopped” because infant mortality has declined sharply across developed, and developing, nations. Evolution understood as change in gene frequencies will continue because there will be sample variance in the proportions of given alleles from generation to generation. But more interestingly adaptive evolution driven by change in mean values of heritable phenotypes through natural selection will also continue, assuming:
1) There is variance in reproductive fitness
2) That that variance is correlated with a phenotype
3) That those phenotypes are at all heritable. In other words, phenotypic variation tracks genotypic variation
Obviously there is variance in reproductive fitness. Additionally, most people have the intuition that particular traits are correlated with fecundity, whether it be social-cultural identities, or personality characteristics. The main issue is probably #3. It is a robust finding for example that in developed societies the religious tend to have more children than the irreligious. If there is an innate predisposition to religiosity, and there is some research which suggests modest heritability, then all things being equal the population would presumably be shifting toward greater innate predisposition toward religion as time passes. I do believe religiosity is heritable to some extent. More precisely I think there are particular psychological traits which make supernatural claims more plausible for some than others, and, those traits themselves are partially determined by biology. But obviously even if we think that religious inclination is partially heritable in a biological sense, it is also heritable in the familial sense of values passed from one generation to the next, and in a broader cultural context of norms imposed from on high. In other words, when it comes to these sorts of phenotypic analyses we shouldn’t get too carried away with clean genetic logics. In Shall the Religious Inherit the Earth? Eric Kaufmann notes that it is in the most secular nations that the fertility gap between the religious and irreligious is greatest, and therefore selection for religiosity would be strongest in nations such as Sweden, not Saudi Arabia. But as a practical matter biologically driven shifts in trait value in this case pales in comparison to the effect of strong cultural norms for religiosity.
Below are two of the topline tables which show the traits which are currently subject to natural selection. A + sign indicates that there is natural selection for higher values of the trait, and a – sign the inverse. An s indicates stabilizing selection, which tells you that median values have higher fitnesses than the extremes. The number of stars is proportional to statistical significance.
One of the major issues which has loomed at the heart of biology since The Origin of Species is why species exist, as well as how species come about. Why isn’t there a perfect replicator which performs all the conversion of energy and matter into biomass on this planet? If there is a God the tree of life almost seems to be a testament to his riotous aesthetic sense, with numerous branches which lead to convergences, and a inordinate fascination with variants on the basic morph of beetles. From the outside the outcomes of evolutionary biology look a patent mess, a sprawling expanse of experiments and misfires.
A similar issue has vexed biologists in relation to sex. Why is it that the vast majority of complex organisms take upon themselves the costs of sex? The existence of a non-offspring bearing form within a species reduces the potential natural increase by a factor of two before the game has even begun. Not only that, but the existence of two sexes who must seek each other out expends crucial energy in a Malthusian world (selfing hermaphrodites obviously don’t have this problem, but for highly complex organisms they aren’t so common). Why bother? (I mean in an ultimate, not proximate, sense)
It seems likely that part of the answer to both these questions on the grande scale is that the perfect is the enemy of long term survival. Sexual reproduction confers upon a lineage a genetic variability which may reduce fitness by shifting populations away from the adaptive peak in the short term, but the fitness landscape itself is a constant bubbling flux, and perfectly engineered asexual lineages may all too often fall off the cliff of what was once their mountain top. The only inevitability seems to be that the times change. Similarly, the natural history of life on earth tells us that all greatness comes to an end, and extinction is the lot of life. The universe is an unpredictable place and the mighty invariably fall, as the branches of life’s tree are always pruned by the gardeners red in tooth and claw.
But it is one thing to describe reality in broad verbal brushes. How about a more rigorous empirical and theoretical understanding of how organisms and the genetic material through which they gain immortality play out in the universe? A new paper which uses plant models explores the costs and benefits of admixture between lineages, and how those two dynamics operate in a heterogeneous and homogeneous world. Population admixture, biological invasions and the balance between local adaptation and inbreeding depression:
How we perceive nature and describe its shape are a matter of values and preferences. Nature does not take notice of our distinctions; they exist only as instruments which aid in our comprehension. I’ve brought this up in relation to issues such as categorization of recessive vs. dominant traits. The offspring of people of Sub-Saharan African and non-African ancestry where the non-African parent has straight or wavy hair tend to have very curly hair. Therefore, one may say that the tightly curled hair form is dominant to straight or wavy hair. But, it is also the case that there is some modification in relation to the African parent in the offspring, so the dominance is not complete. When examining the morphology of the follicle, which determines the extent of the hair’s curl, the offspring may in fact exhibit some differences from both parents. In other words our perception of the outcomes of inheritance are contingent to some extent on our categorization of the traits as well as our specific focus along the developmental pathway.
Or consider the division between “traits” and “diseases.” The quotations are necessary. Lactose intolerance is probably one of the best cases to illustrate the gnarly normative obstructions which warp our perceptions. As a point of fact lactose intolerance is the ancestral human state, and numerically predominant. It is the “wild type.” Lactose tolerance is a relatively recent adaptation, found among a variety of West Eurasian and African populations. A more politically correct term, lactase persistence, probably better encapsulates the evolutionary history of the trait, which has shifted from the class of disease to that of genetic trait when we evaluate the bigger picture (obviously diseases are simply “bad” traits”).
Mutations are as you know a double-edged sword. On the one hand mutations are the stuff of evolution; neutral changes on the molecular or phenotypic level are the result of from mutations, as are changes which enhance fitness and so are driven to fixation by positive selection. On the other hand mutations also tend to cause problems. In fact, mutations which are deleterious far outnumber those which are positive. It is much easier to break complex systems which are near a fitness optimum than it is to improve upon them through random chance. In fact a Fisherian geometric analogy of the affect of genes on fitness implies that once a genetic configuration nears an optimum mutations of larger effect have a tendency to decrease fitness. Sometimes environments and selection pressures change radically, and large effect mutations may become needful. But despite their short term necessity these mutations still cause major problems because they disrupt many phenotypes due to pleiotropy.
But much of the playing out of evolutionary dynamics is not so dramatic. Instead of very costly mutations for good or ill, most mutations may be of only minimal negative effect, especially if they are masked because of recessive expression patterns. That is, only when two copies of the mutation are present does all hell break loose. And yet even mutations which exhibit recessive expression tend to generate some drag on the fitness of heterozygotes. And if you sum small values together you can obtain a larger value. This gentle rain of small negative effect mutations can be balanced by natural selection, which weeds does not smile upon less fit individuals who have a higher mutational load. Presumably those with “good genes,” fewer deleterious mutations, will have more offspring than those with “bad genes.” Because mutations accrue from one generation to the next, and, there is sampling variance of deleterious alleles, a certain set of offspring will always be gifted with fewer deleterious mutations than their siblings. This is a genetics of chance. And so the mutation-selection balance is maintained over time, the latter rising to the fore if the former comes to greater prominence.
The above has been a set of logic inferences from premises. Evolution is about the logic of life’s process, but as a natural science its beauty is that it is testable through empirical means. A short report in Science explores mutational load and fitness, and connects it with the ever popular topic of sexual selection, Additive Genetic Breeding Values Correlate with the Load of Partially Deleterious Mutations:
You probably are aware that different populations have different tolerances for high altitudes. Himalayan sherpas aren’t useful just because they have skills derived from their culture, they’re actually rather well adapted to high altitudes because of their biology. Additionally, different groups seem to have adapted to higher altitudes independently, exhibiting convergent evolution. But in terms of physiological function they aren’t all created equal, at least in relation to the solutions which they’ve come to to make functioning at high altitudes bearable. In particular, it seems that the adaptations of the peoples of Tibet are superior than those of the peoples of the Andes. Superior in that the Andean solution is more brute force than the Tibetan one, producing greater side effects, such as lower birth weight in infants (and so higher mortality and lower fitness).
The Andean region today is dominated by indigenous people, and Spanish is not the lingua franca of the highlands as it is everyone in in the former colonial domains of Spain in the New World. This is largely a function of biology; as in the lowlands of South America the Andean peoples were decimated by disease upon first contact (plague was spreading across the Inca Empire when Pizzaro arrived with his soldiers). But unlike the lowland societies the Andeans had nature on their side: people of mixed or European ancestry are less well adapted to high altitudes and women without tolerance of the environment still have higher miscarriage rates.