Adaptation and speciation: what can F-st tell us?

A useful way of summarizing genetic variability among different populations is through estimates of the inbreeding coefficient, F-st. Several recent studies have tried to use the distribution of estimates of F-st from individual genetic loci to detect the effects of natural selection. However, the promise of this approach has yet to be fully realized owing to the pervasive dogma that this distribution is highly dependent on demographic history. Here, I review recent theoretical results that indicate that the distribution of estimates of F-st is generally expected to be robust to the vagaries of demographic history. I suggest that analyses based on it provide a useful first step for identifying candidate genes that might be under selection, and explore the ways in which this information can be used in ecological and evolutionary studies.

Recent developments in genetic data analysis: what can they tell us about human demographic history?

Over the last decade, a number of new methods of population genetic analysis based on likelihood have been introduced. This review describes and explains the general statistical techniques that have recently been used, and discusses the underlying population genetic models. Experimental papers that use these methods to infer human demographic and phylogeographic history are reviewed. It appears that the use of likelihood has hitherto had little impact in the field of human population genetics, which is still primarily driven by more traditional approaches. However, with the current uncertainty about the effects of natural selection, population structure and ascertainment of single-nucleotide polymorphism markers, it is suggested that likelihood-based methods may have a greater impact in the future.

Identifying adaptive genetic divergence among populations from genome scans

The identification of signatures of natural selection in genomic surveys has become an area of intense research, stimulated by the increasing ease with which genetic markers can be typed. Loci identified as subject to selection may be functionally important, and hence (weak) candidates for involvement in disease causation. They can also be useful in determining the adaptive differentiation of populations, and exploring hypotheses about speciation. Adaptive differentiation has traditionally been identified from differences in allele frequencies among different populations, summarised by an estimate of F-ST. Low outliers relative to an appropriate neutral population-genetics model indicate loci subject to balancing selection, whereas high outliers suggest adaptive (directional) selection. However, the problem of identifying statistically significant departures from neutrality is complicated by confounding effects on the distribution of F-ST estimates, and current methods have not yet been tested in large-scale simulation experiments. Here, we simulate data from a structured population at many unlinked, diallelic loci that are predominantly neutral but with some loci subject to adaptive or balancing selection. We develop a hierarchical-Bayesian method, implemented via Markov chain Monte Carlo (MCMC), and assess its performance in distinguishing the loci simulated under selection from the neutral loci. We also compare this performance with that of a frequentist method, based on moment-based estimates of F-ST. We find that both methods can identify loci subject to adaptive selection when the selection coefficient is at least five times the migration rate. Neither method could reliably distinguish loci under balancing selection in our simulations, even when the selection coefficient is twenty times the migration rate.

The lay of the trilobite: rereading May Kendall

The impact of Darwin's theory of evolution by natural selection on the culture of late Victorian England and on the development of Western thought at large is at once widely acknowledged and hotly contested. In this essay, I revisit the question of what difference an understanding of Darwin's ideas, their reception and their afterlife within evolutionary biology makes to how we read Victorian poetry. I suggest that there are three distinct ways of approaching poetry after Darwin. The first is to examine poems in their own cultural context, considering how they respond to the scientific discourses of their time in the light of internal and external evidence as to the specific sources of each poet's knowledge of those discourses. The second is to ground an interpretative framework in Darwinism's insights into human biology itself. The third is to explore how a given poem's responses to the philosophical issues raised by Darwin's thinking, including questions of ethics and theology, give its readers a possible model for their own responses to the same concerns today. I suggest too that the limitations of each approach may be best overcome by bringing them together. I go on to explore the potential of the first and third approaches through a reading of May Kendall's poem 'The Lay of the Trilobite' in a series of different contexts, from its first appearance in 'Punch', through her first collection Dreams to Sell, to her essays on Christian ethics from the 1880s and 1890s

Speciation as an active force in promoting genetic evolution

There is a growing appreciation among evolutionary biologists that the rate and tempo of molecular evolution might often be altered at or near the time of speciation, i.e. that speciation is in some way a special time for genes. Molecular phylogenies frequently reveal increased rates of genetic evolution associated with speciation and other lines of investigation suggest that various types of abrupt genomic disruption can play an important role in promoting speciation via reproductive isolation. These phenomena are in conflict with the gradual view of molecular evolution that is implicit in much of our thinking about speciation and in the tools of modern biology. This raises the prospect of studying the molecular evolutionary consequences of speciation per se and studying the footprint of speciation as an active force in promoting genetic divergence. Here we discuss the reasons to believe that speciation can play such a role and elaborate on possible mechanisms for accelerated rates of evolution following speciation. We provide an example of how it is possible detect whether accelerated bursts of evolution occur in neutral and/or adaptive regions of genes and discuss the implications of rapid episodes of change for conventional models of molecular evolution. Speciation might often owe more to ephemeral and essentially arbitrary events that cause reproductive isolation than to the gradual and regular tug of natural selection that draws a species into a new niche.

Selfishness and altruism can coexist when help is subject to diminishing returns

Altruism and selfishness are 30–50% heritable in man in both Western and non-Western populations. This genetically based variation in altruism and selfishness requires explanation. In non-human animals, altruism is generally directed towards relatives, and satisfies the condition known as Hamilton's rule. This nepotistic altruism evolves under natural selection only if the ratio of the benefit of receiving help to the cost of giving it exceeds a value that depends on the relatedness of the individuals involved. Standard analyses assume that the benefit provided by each individual is the same but it is plausible in some cases that as more individuals contribute, help is subject to diminishing returns. We analyse this situation using a single-locus two-allele model of selection in a diploid population with the altruistic allele dominant to the selfish allele. The analysis requires calculation of the relationship between the fitnesses of the genotypes and the frequencies of the genes. The fitnesses vary not only with the genotype of the individual but also with the distribution of phenotypes amongst the sibs of the individual and this depends on the genotypes of his parents. These calculations are not possible by direct fitness or ESS methods but are possible using population genetics. Our analysis shows that diminishing returns change the operation of natural selection and the outcome can now be a stable equilibrium between altruistic and selfish alleles rather than the elimination of one allele or the other. We thus provide a plausible genetic model of kin selection that leads to the stable coexistence in the same population of both altruistic and selfish individuals. This may explain reported genetic variation in altruism in man.

Multiple routes to mammalian diversity

The radiation of the mammals provides a 165-million-year test case for evolutionary theories of how species occupy and then fill ecological niches. It is widely assumed that species often diverge rapidly early in their evolution, and that this is followed by a longer, drawn-out period of slower evolutionary fine-tuning as natural selection fits organisms into an increasingly occupied niche space1,2. But recent studies have hinted that the process may not be so simple3–5. Here we apply statistical methods that automatically detect temporal shifts in the rate of evolution through time to a comprehensive mammalian phylogeny6 and data set7 of body sizes of 3,185 extant species. Unexpectedly, the majority of mammal species, including two of the most speciose orders (Rodentia and Chiroptera), have no history of substantial and sustained increases in the rates of evolution. Instead, a subset of the mammals has experienced an explosive increase (between 10- and 52-fold) in the rate of evolution along the single branch leading to the common ancestor of their monophyletic group (for example Chiroptera), followed by a quick return to lower or background levels. The remaining species are a taxonomically diverse assemblage showing a significant, sustained increase or decrease in their rates of evolution. These results necessarily decouple morphological diversification from speciation and suggest that the processes that give rise to the morphological diversity of a class of animals are far more free to vary than previously considered. Niches do not seem to fill up, and diversity seems to arise whenever, wherever and at whatever rate it is advantageous.

First steps in experimental cancer evolution

Evolutionary processes play a central role in the development, progression and response to treatment of cancers. The current challenge facing researchers is to harness evolutionary theory to further our understanding of the clinical progression of cancers. Central to this endeavour will be the development of experimental systems and approaches by which theories of cancer evolution can be effectively tested. We argue here that the experimental evolution approach – whereby evolution is observed in real time and which has typically employed microorganisms – can be usefully applied to cancer. This approach allows us to disentangle the ecological causes of natural selection, identify the genetic basis of evolutionary changes and determine their repeatability. Cell cultures used in cancer research share many of the desirable traits that make microorganisms ideal for studying evolution. As such, experimental cancer evolution is feasible and likely to give great insight into the selective pressures driving the evolution of clinically destructive cancer traits. We highlight three areas of evolutionary theory with importance to cancer biology that are amenable to experimental evolution: drug resistance, social evolution and resource competition. Understanding the diversity, persistence and evolution of cancers is vital for treatment and drug development, and an experimental evolution approach could provide strategic directions and focus for future research.

Evolutionary resurrection of flagellar motility via rewiring of the nitrogen regulation system

A central process in evolution is the recruitment of genes to regulatory networks. We engineered immotile strains of the bacterium Pseudomonas fluorescens that lack flagella due to deletion of the regulatory gene fleQ. Under strong selection for motility, these bacteria consistently regained flagella within 96 hours via a two-step evolutionary pathway. Step 1 mutations increase intracellular levels of phosphorylated NtrC, a distant homologue of FleQ, which begins to commandeer control of the fleQ regulon at the cost of disrupting nitrogen uptake and assimilation. Step 2 is a switch-of-function mutation that redirects NtrC away from nitrogen uptake and towards its novel function as a flagellar regulator. Our results demonstrate that natural selection can rapidly rewire regulatory networks in very few, repeatable mutational steps.

Contrasting phylogenetic signals and evolutionary rates in floral traits of Neotropical lianas

The diversity of floral forms has long been considered a prime example of radiation through natural selection. However, little is still known about the evolution of floral traits, a critical piece of evidence for the understanding of the processes that may have driven flower evolution. We studied the pattern of evolution of quantitative floral traits in a group of Neotropical lianas (Bignonieae, Bignoniaceae) and used a time-calibrated phylogeny as basis to: (1) test for phylogenetic signal in 16 continuous floral traits; (2) evaluate the rate of evolution in those traits; and (3) reconstruct the ancestral state of the individual traits. Variation in floral traits among extant species of Bignonieae was highly explained by their phylogenetic history. However, opposite signals were found in floral traits associated with the attraction of pollinators (calyx and corolla) and pollen transfer (androecium and gynoecium), suggesting a differential role of selection in different floral whorls. Phylogenetic independent contrasts indicate that traits evolved at different rates, whereas ancestral character state reconstructions indicate that the ancestral size of most flower traits was larger than the mean observed sizes of the same traits in extant species. The implications of these patterns for the reproductive biology of Bignonieae are discussed. (C) 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 102, 378-390.

Mating system and exclusive postzygotic paternal care in a Neotropical harvestman (Arachnida: Opiliones)

This study tests predictions of the hypothesis of evolution of paternal care via sexual selection by using the Neotropical harvestman Pseudopucrolia sp. as the model organism. Females use natural cavities in roadside banks as nesting sites, which are defended by males against other males. Females leave the nests after oviposition, and all postzygotic parental care is accomplished by males, which protect the eggs and nymphs from predators. We provided artificial mud nests to individuals in the laboratory and conducted observations on the reproduction of the species. Male reproductive success was directly related to nest ownership time: the longer a male held a nest, the higher his chances of obtaining copulations. All males that succeeded in mating and obtaining one clutch eventually mated with additional females that added eggs to the clutch. Thus, desirable males were not limited to monogamy by paternal care. Experimental manipulations demonstrated that guarding males were more attractive to females than were nonguarding males and also that males guarded unrelated eggs. Finally, we found that females and nonguarding males spent more time foraging than guarding males. We use our data to contrast hypotheses on the origin and maintenance of paternal care and to provide a critical assessment of the hypothesis of the evolution of paternal care via sexual selection. (C) 2009 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.

Relation of pretreatment sequence diversity in NS5A region of HCV genotype 1 with immune response between pegylated-INF/ribavirin therapy outcomes

Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific immune responses and the combination of pegylated interferon (INF)-alpha and ribavirin therapy. Major histocompatibility complex class I restricted CD8+ T cells are responsible for the control of viraemia in HCV infection, and several studies suggest protection against viral infection associated with specific HLAs. The reason for low rates of sustained viral response (SVR) in HCV patients remains unknown. Escape mutations in response to cytotoxic T lymphocyte are widely described; however, its influence in the treatment outcome is ill understood. Here, we investigate the differences in CD8 epitopes frequencies from the Los Alamos database between groups of patients that showed distinct response to pegylated alpha-INF with ribavirin therapy and test evidence of natural selection on the virus in those who failed treatment, using five maximum likelihood evolutionary models from PAML package. The group of sustained virological responders showed three epitopes with frequencies higher than Non-responders group, all had statistical support, and we observed evidence of selection pressure in the last group. No escape mutation was observed. Interestingly, the epitope VLSDFKTWL was 100% conserved in SVR group. These results suggest that the response to treatment can be explained by the increase in immune pressure, induced by interferon therapy, and the presence of those epitopes may represent an important factor in determining the outcome of therapy.

Balanced polymorphism in bottlenecked populations: The case of the CCR5 5 ` cis-regulatory region in Amazonian Amerindians

The 5` cis-regulatory region of the CCR5 gene exhibits a strong signature of balancing selection in several human populations. Here we analyze the polymorphism of this region in Amerindians from Amazonia, who have a complex demographic history, including recent bottlenecks that are known to reduce genetic variability. Amerindians show high nucleotide diversity (pi = 0.27%) and significantly positive Tajima`s D, and carry haplotypes associated with weak and strong gene expression. To evaluate whether these signatures of balancing selection could be explained by demography, we perform neutrality tests based on empiric and simulated data. The observed Tajima`s D was higher than that of other world populations: higher than that found for 18 noncoding regions of South Amerindians, and higher than 99.6% of simulated genealogies, which assume nonequilibrium conditions. Moreover, comparing Amerindians and Asians, the Fst for CCR5 cis-regulatory region was unusually low, in relation to neutral markers. These findings indicate that, despite their complex demographic history, South Amerindians carry a detectable signature of selection on the CCR5 cis-regulatory region. (C) 2010 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Craniometric Similarities Within and Between Human Populations in Comparison with Neutral Genetic Data

The statement that pairs of individuals from different populations are often more genetically similar than pairs from the same population is a widespread idea inside and outside the scientific community. Witherspoon et al. [""Genetic similarities within and between human populations,"" Genetics 176:351-359 (2007)] proposed an index called the dissimilarity fraction (omega) to access in a quantitative way the validity of this statement for genetic systems. Witherspoon demonstrated that, as the number of loci increases, omega decreases to a point where, when enough sampling is available, the statement is false. In this study, we applied the dissimilarity fraction to Howells`s craniometric database to establish whether or not similar results are obtained for cranial morphological traits. Although in genetic studies thousands of loci are available, Howells`s database provides no more than 55 metric traits, making the contribution of each variable important. To cope with this limitation, we developed a routine that takes this effect into consideration when calculating. omega Contrary to what was observed for the genetic data, our results show that cranial morphology asymptotically approaches a mean omega of 0.3 and therefore supports the initial statement-that is, that individuals from the same geographic region do not form clear and discrete clusters-further questioning the idea of the existence of discrete biological clusters in the human species. Finally, by assuming that cranial morphology is under an additive polygenetic model, we can say that the population history signal of human craniometric traits presents the same resolution as a neutral genetic system dependent on no more than 20 loci.

Population genetic analysis of large sequence polymorphisms in Plasmodium falciparum blood-stage antigens

Plasmodium falciparum, the causative agent of human malaria, invades host erythrocytes using several proteins on the surface of the invasive merozoite, which have been proposed as potential vaccine candidates. Members of the multi-gene PfRh family are surface antigens that have been shown to play a central role in directing merozoites to alternative erythrocyte receptors for invasion. Recently, we identified a large structural polymorphism, a 0.58 Kb deletion, in the C-terminal region of the PfRh2b gene, present at a high frequency in parasite populations from Senegal. We hypothesize that this region is a target of humoral immunity. Here, by analyzing 371 P. falciparum isolates we show that this major allele is present at varying frequencies in different populations within Senegal, Africa, and throughout the world. For allelic dimorphisms in the asexual stage antigens, Msp-2 and EBA-175, we find minimal geographic differentiation among parasite populations from Senegal and other African localities, suggesting extensive gene flow among these populations and/or immune-mediated frequency-dependent balancing selection. In contrast, we observe a higher level of inter-population divergence (as measured by F(st)) for the PfRh2b deletion, similar to that observed for SNPs from the sexual stage Pfs45/48 loci, which is postulated to be under directional selection. We confirm that the region containing the PfRh2b polymorphism is a target of humoral immune responses by demonstrating antibody reactivity of endemic sera. Our analysis of inter-population divergence suggests that in contrast to the large allelic dimorphisms in EBA-175 and Msp-2, the presence or absence of the large PfRh2b deletion may not elicit frequency-dependent immune selection, but may be under positive immune selection, having important implications for the development of these proteins as vaccine candidates. (C) 2009 Elsevier B.V. All rights reserved.