The PNarec method for detection of ancient recombinations through phylogenetic network analysis

Recombinations are known to disrupt bifurcating tree structure of gene genealogies. Although recently occurred recombinations are easily detectable by using conventional methods, recombinations may have occurred at any time. We devised a new method for detecting ancient recombinations through phylogenetic network analysis, and detected five ancient recombinations in gibbon ABO blood group genes [Kitano et al., 2009. Mol. Phylogenet. Evol., 51, 465–471]. We present applications of this method, now named as “PNarec”, to various virus sequences as well as HLA genes.     

The performance of phylogenetic algorithms in estimating haplotype genealogies with migration

Genealogies estimated from haplotypic genetic data play a prominent role in various biological disciplines in general and in phylogenetics, population genetics and phylogeography in particular. Several software packages have specifically been developed for the purpose of reconstructing genealogies from closely related, and hence, highly similar haplotype sequence data. Here, we use simulated data sets to test the performance of traditional phylogenetic algorithms, neighbour-joining, maximum parsimony and maximum likelihood in estimating genealogies from nonrecombining haplotypic genetic data. We demonstrate that these methods are suitable for constructing genealogies from sets of closely related DNA sequences with or without migration. As genealogies based on phylogenetic reconstructions are fully resolved, but not necessarily bifurcating, and without reticulations, these approaches outperform widespread 'network' constructing methods. In our simulations of coalescent scenarios involving panmictic, symmetric and asymmetric migration, we found that phylogenetic reconstruction methods performed well, while the statistical parsimony approach as implemented in TCS performed poorly. Overall, parsimony as implemented in the PHYLIP package performed slightly better than other methods. We further point out that we are not making the case that widespread 'network' constructing methods are bad, but that traditional phylogenetic tree finding methods are applicable to haplotypic data and exhibit reasonable performance with respect to accuracy and robustness. We also discuss some of the problems of converting a tree to a haplotype genealogy, in particular that it is nonunique.     

Ancestral Stories of Ghanaian Bimoba Reflect Millennia-Old Genetic Lineages

Oral history and oral genealogies are mechanisms of collective memory and a main cultural heritage of many populations without a writing system. In the effort to analytically address the correspondence between genetic data and historical genealogies, anthropologists hypothesised that genealogies evolve through time, ultimately containing three parts: literal – where the most recent ancestry is truthfully represented; intended – where ancestry is inferred and reflects political relations among groups; and mythical – that does not represent current social reality. While numerous studies discuss oral genealogies, to our knowledge no genetic studies have been able to investigate to what extent genetic relatedness corresponds to the literal and intended parts of oral genealogies. We report on the correspondence between genetic data and oral genealogies among Bimoba males in a single village in North-Eastern Ghana. We compared the pairwise mismatch distribution of Y chromosome short tandem repeat (Y-STR) haplotypes among all lineages present in this village to the self-reported (oral) relatedness. We found that Bimoba are able to correctly identify unrelated individuals in 92% of the cases. In contrast, they are able to correctly identify related individuals only in 38% of the cases, which can be explained by three processes: (1) the compression of genealogies, leading to increasing inaccuracy with increasing genealogical distance, (2) inclusions into the lineage from intended relations such as clan co-option or adoptions, and (3) false paternities, which in this study were found to have a minor effect on the correspondence between genetic data and oral genealogies. In addition, we observed that 70% of unrelated pairs have from six to eight Y-STR differences, a diversification peak which we attribute to an ancient West African expansion dating around 9454 years ago. We conclude that, despite all caveats, oral genealogies are reflecting ancient lineages more accurately than previously thought.     

Variance in intrinsic rates of growth among free-ranging rhesus monkey groups

Differential rates of intrinsic growth for the population of Macaca mulatta on Cayo Santiago partitioned by social group and dominance rank of genealogies indicate that the potential for increase is not uniformly distributed throughout the population. In the period from 1973 to 1974, high-ranking genealogies were growing at a faster rate than low-ranking genealogies. Large differences in r among the social groups indicate the possible existence of demographic, genetic, or social differences between groups. A random resampling procedure was employed to assess the statistical significance of differences in the intrinsic rate of growth among the 5 natural social groups and the 3 partitions formed by, respectively, lumping members of high-, middle-, and low-ranking genealogies across several social groups. Comparisons among social groups shows that there are significant differences in the rate of growth between Group J and Group M, and between Group J and Group F for the period from 1973 to 1974. Among dominance ranks of genealogies, significant differences in r were found between the partitions of the high- and middle-ranking genealogies. These findings suggest that differential reproductive success is influenced and maintained by underlying variations in the distribution of behavioral traits in the population.     

Methodology of reconstruction and preliminary analysis of 1533 genealogies of parma valley population (centuries XVI–XX)

The reconstruction of the genealogies and the detailed knowledge of the biological and kinship relationship linking the past and the present members of a population and their succession in time, can be a precious source of information for those who want to reconstruct and analyze biological and cultural mechanisms by which human populations evolve and adapt to environmental changes.The methods used for the reconstruction of the genealogies are described and an analysis of the results obtained is presented in order to test the validity of the techniques employed on the basis of the reliability of the results.Finally, a discussion of some possible lines of research derived from analysis of the data are presented, given that the use of genealogies, far from being restricted to the genealogies themselves, can offer a valid contribution to the analysis of the structure and evolution of human populations.     

Sampling HIV Intrahost Genealogies Based on a Model of Acute Stage CTL Response

Cytotoxic T lymphocytes (CTLs) play an important role in the immune response to HIV during the acute stage of infection, but the effect of CTLs on HIV intrahost genetic diversity is poorly understood. We introduce a model of CTL attack during the acute stage. Assuming this model, we develop a method to sample HIV intrahost genealogies. Using our sampling approach, we characterize the evolutionary forces that shape HIV genealogies. In particular, we show that early mutation events can have significant impact on HIV genealogies and that certain types of CTL attack are best at controlling HIV genetic diversity. Our sampler represents a first step toward using HIV genetic data to infer properties of CTL attack.     

Conditional gene genealogies under strong purifying selection

The ancestral selection graph, conditioned on the allelic types in the sample, is used to obtain a limiting gene genealogical process under strong selection. In an equilibrium, two-allele system with strong selection, neutral gene genealogies are predicted for random samples and for samples containing at most one unfavorable allele. Samples containing more than one unfavorable allele have gene genealogies that differ greatly from neutral predictions. However, they are related to neutral gene genealogies via the well-known Ewens sampling formula. Simulations show rapid convergence to limiting analytical predictions as the strength of selection increases. These results extend the idea of a soft selective sweep to deleterious alleles and have implications for the interpretation of polymorphism among disease-causing alleles in humans.     

Phylodynamic Inference for Structured Epidemiological Models

Coalescent theory is routinely used to estimate past population dynamics and demographic parameters from genealogies. While early work in coalescent theory only considered simple demographic models, advances in theory have allowed for increasingly complex demographic scenarios to be considered. The success of this approach has lead to coalescent-based inference methods being applied to populations with rapidly changing population dynamics, including pathogens like RNA viruses. However, fitting epidemiological models to genealogies via coalescent models remains a challenging task, because pathogen populations often exhibit complex, nonlinear dynamics and are structured by multiple factors. Moreover, it often becomes necessary to consider stochastic variation in population dynamics when fitting such complex models to real data. Using recently developed structured coalescent models that accommodate complex population dynamics and population structure, we develop a statistical framework for fitting stochastic epidemiological models to genealogies. By combining particle filtering methods with Bayesian Markov chain Monte Carlo methods, we are able to fit a wide class of stochastic, nonlinear epidemiological models with different forms of population structure to genealogies. We demonstrate our framework using two structured epidemiological models: a model with disease progression between multiple stages of infection and a two-population model reflecting spatial structure. We apply the multi-stage model to HIV genealogies and show that the proposed method can be used to estimate the stage-specific transmission rates and prevalence of HIV. Finally, using the two-population model we explore how much information about population structure is contained in genealogies and what sample sizes are necessary to reliably infer parameters like migration rates.     

Oscillatory flow and gas transport through a symmetrical bifurcation

Axial gas transport due to the interaction between radial mixing and radially nonuniform axial velocities is responsible for gas transport in thick airways during High-frequency oscillatory ventilation (HFO). Because the airways can be characterized by a bifurcating tube network, the secondary flow in the curved portion of a bifurcating tube contributes to cross-stream mixing. In this study the oscillatory flow and concentration fields through a single symmetrical airway bifurcating tube model were numerically analyzed by solving three-dimensional Navier-Stokes and mass concentration equations with the SIMPLER algorithm. The simulation conditions were for a Womersley number, alpha = 9.1 and Reynolds numbers in the parent tube between 200 and 1000, corresponding to Dn2/alpha 4 in the curved portion between 2 and 80, where Dn is Dean number. For comparison with the results from the bifurcating tube, we calculated the velocity and concentration fields for fully developed oscillatory flow through a curved tube with a curvature rate of 1/10, which is identical to the curved portion of the bifurcating tube. For Dn2/alpha 4 < or = 10 in the curved portion of the bifurcating tube, the flow divider and area changes dominate the axial gas transport, because the effective diffusivity is greater than in either a straight or curved tube, in spite of low secondary velocities. However, for Dn2/alpha 4 > or = 20, the gas transport characteristics in a bifurcation are similar to a curved tube because of the significant effect of secondary flow.     

AUGIST: inferring species trees while accommodating gene tree uncertainty

SUMMARY: AUGIST (accomodating uncertainty in genealogies while inferring species tress) is a new software package for inferring species trees while accommodating uncertainty in gene genealogies. It is written for the Mesquite software system and provides sampling procedures to incorporate uncertainty in gene tree reconstruction while providing confidence estimates for inferred species trees. AVAILABILITY: http://www.lycaenid.org/augist/     

Mathematical models and computer simulations of proliferation of human diploid fibroblast clones.

A mathematical model based on the simple concept of an oscillatory mechanism for regulation of cellular proliferation has been developed that describes the growth of clones of human diploid fibroblasts in vitro. Lineages of these cells have been obtained from time-lapse cinematographic sequences of proliferating clones. Computer simulations based upon the oscillator model have generated genealogies that behave as the experimentally-derived genealogies.     

Integrated thermodynamic analysis of electron bifurcating [FeFe]-hydrogenase to inform anaerobic metabolism and H2 production

Electron bifurcating, [FeFe]-hydrogenases are recently described members of the hydrogenase family and catalyze a combination of exergonic and endergonic electron exchanges between three carriers (2 ferredoxin_red⁻ + NAD(P)H + 3 H⁺ = 2 ferredoxin_ox + NAD(P)⁺ + 2 H₂). A thermodynamic analysis of the bifurcating, [FeFe]-hydrogenase reaction, using electron path-independent variables, quantified potential biological roles of the reaction without requiring enzyme details. The bifurcating [FeFe]-hydrogenase reaction, like all bifurcating reactions, can be written as a sum of two non-bifurcating reactions. Therefore, the thermodynamic properties of the bifurcating reaction can never exceed the properties of the individual, non-bifurcating, reactions. The bifurcating [FeFe]-hydrogenase reaction has three competitive properties: 1) enabling NAD(P)H-driven proton reduction at pH₂ higher than the concurrent operation of the two, non-bifurcating reactions, 2) oxidation of NAD(P)H and ferredoxin simultaneously in a 1:1 ratio, both are produced during typical glucose fermentations, and 3) enhanced energy conservation (~10 kJ mol⁻¹ H₂) relative to concurrent operation of the two, non-bifurcating reactions. Our analysis demonstrated ferredoxin E°′ largely determines the sensitivity of the bifurcating reaction to pH₂, modulation of the reduced/oxidized electron carrier ratios contributed less to equilibria shifts. Hydrogenase thermodynamics data were integrated with typical and non-typical glycolysis pathways to evaluate achieving the ‘Thauer limit’ (4 H₂ per glucose) as a function of temperature and pH₂. For instance, the bifurcating [FeFe]-hydrogenase reaction permits the Thauer limit at 60 °C if pH ₂ ≤ ~10 mbar. The results also predict Archaea, expressing a non-typical glycolysis pathway, would not benefit from a bifurcating [FeFe]-hydrogenase reaction; interestingly, no Archaea have been observed experimentally with a [FeFe]-hydrogenase enzyme.     

Sequence diversity in the tetraploid Zea perennis and the closely related diploid Z. diploperennis: insights from four nuclear loci

Polyploidy has been an extremely common phenomenon in the evolutionary history of angiosperms. Despite this there are few data available to evaluate the effects of polyploidy on genetic diversity and to compare the relative effects of drift and selection in polyploids and related diploids. We investigated DNA sequence diversity at four nuclear loci (adh1, glb1, c1, and waxy) from the tetraploid Zea perennis and the closely related diploid Z. diploperennis. Contrary to expectations, we detected no strong evidence for greater genetic diversity in the tetraploid, or for consistent differences in the effects of either drift or selection between the tetraploid and the diploid. Our failure to find greater genetic diversity in Z. perennis may result from its relatively recent origin or demographic factors associated with its origin. In addition to comparing genetic diversity in the two species, we constructed genealogies to infer the evolutionary origin of Z. perennis. Although these genealogies are equivocal regarding the mode of origin, several aspects of these genealogies support an autotetraploid origin. Consistent with previous molecular data the genealogies do not, however, support the division of Zea into two sections, the section Zea and the section Luxuriantes.     

Branching,blending, and the evolution of cultural similarities and differences among human populations

It has been claimed that blending processes such as trade and exchange have always been more important in the evolution of cultural similarities and differences among human populations than the branching process of population fissioning. In this paper, we report the results of a novel comparative study designed to shed light on this claim. We fitted the bifurcating tree model that biologists use to represent the relationships of species to 21 biological data sets that have been used to reconstruct the relationships of species and/or higher level taxa and to 21 cultural data sets. We then compared the average fit between the biological data sets and the model with the average fit between the cultural data sets and the model. Given that the biological data sets can be confidently assumed to have been structured by speciation, which is a branching process, our assumption was that, if cultural evolution is dominated by blending processes, the fit between the bifurcating tree model and the cultural data sets should be significantly worse than the fit between the bifurcating tree model and the biological data sets. Conversely, if cultural evolution is dominated by branching processes, the fit between the bifurcating tree model and the cultural data sets should be no worse than the fit between the bifurcating tree model and the biological data sets. We found that the average fit between the cultural data sets and the bifurcating tree model was not significantly different from the fit between the biological data sets and the bifurcating tree model. This indicates that the cultural data sets are not less tree-like than are the biological data sets. As such, our analysis does not support the suggestion that blending processes have always been more important than branching processes in cultural evolution. We conclude from this that, rather than deciding how cultural evolution has proceeded a priori, researchers need to ascertain which model or combination of models is relevant in a particular case and why.     

Genealogies as Culture and Biology: a Tokelau Case Study

It has become dogma among cultural anthropologists that genealogies are primarily political documents which do not necessarily give reliable accounts of actual biological relationships. This paper examines this assertion in the light of social and serological evidence from one small Polynesian society. It is shown that, within certain limits, Tokelau genealogies do give accurate accounts of biological relationships, and provide a sound basis for interdisciplinary studies which cross the interface between biological and social systems.     

PATTERNS OF DESCENT IN CLONAL LINEAGES AND THEIR MULTILOCUS FINGERPRINTS ARE RESOLVED WITH COMBINED GENE GENEALOGIES

Clonal lineages in the filamentous ascomycete (fungi) Sclerotinia sclerotiorum were determined by analysis of genealogies of four loci: the intergenic spacer of the nuclear ribosomal repeat (IGS; approximately 4 kb), the translation elongation factor (EF-1α; approximately 300 bp), an anonymous region (44.11; approximately 700 bp), and the calmodulin gene (CAL; approximately 400 bp). Three of the four loci are physically unlinked. The combined analysis of the four loci provided the best estimate of phylogeny, which is consistent with a pattern of some recombination among clonal lineages against a background of predominant clonality. Comparison of gene genealogies with a phylogeny inferred from DNA fingerprints and a combined phylogeny of the entire dataset identified convergent or parallel changes in fingerprints. Analysis of the entire data matrix allowed us to resolve patterns of descent among clonal lineages that could not be inferred from fingerprints alone and to discern recent episodes of divergence that were not detected in gene genealogies. Prerequisites for applying this approach to other systems are a haploid context for inferring multiple gene genealogies (such as the mitochondrial genome) that indicate limited recombination and another data matrix that identifies recently evolved genotypes.     

TREES SIFTER 1.0: an approximate method to estimate the time to the most recent common ancestor of a sample of DNA sequences

trees sifter 1.0 implements an approximate method to estimate the time to the most recent common ancestor (TMRCA) of a set of DNA sequences, using population evolution modelling. In essence, the program simulates genealogies with a user‐defined model of coalescence of lineages, and then compares each simulated genealogy to the genealogy inferred from the real data, through two summary statistics: (i) the number of mutations on the genealogy (M_n), and (ii) the number of different sequence types (alleles) observed (K_n). The simulated genealogies are then submitted to a rejection algorithm that keeps only those that are the most likely to have generated the observed sequence data. At the end of the process, the accepted genealogies can be used to estimate the posterior probability distribution of the TMRCA.     

Low nonpaternity rate in an old Afrikaner family

Extrapair paternity is a crucial parameter for evolutionary explanations of reproductive behavior. Early studies and human testis size suggest that human males secure/suffer frequent extrapair paternity. If these high rates are indeed true, it brings into question studies that use genealogies to infer human life history and the history of diseases since the recorded genealogies do not reflect paths of genetic inheritance. We measure the rate of nonpaternity in an old Afrikaner family in South Africa by comparing Y-chromosome short tandem repeats to the genealogy of males. In this population, the nonpaternity rate was 0.73%. This low rate is observed in other studies that matched genealogies to genetic markers and more recent studies that also find estimates below 1%. It may be that imposed religious morals have led to reduced extrapair activities in some historic populations. We also found that the mutation rate is high for this family, but is unrelated to age at conception.     

The reductive half-reaction of two bifurcating electron-transferring flavoproteins: Evidence for changes in flavin reduction potentials mediated by specific conformational changes

The EtfAB components of two bifurcating flavoprotein systems, the crotonyl-CoA-dependent NADH:ferredoxin oxidoreductase from the bacterium Megasphaera elsdenii and the menaquinone-dependent NADH:ferredoxin oxidoreductase from the archaeon Pyrobaculum aerophilum, have been investigated. With both proteins, we find that removal of the electron-transferring flavin adenine dinucleotide (FAD) moiety from both proteins results in an uncrossing of the reduction potentials of the remaining bifurcating FAD; this significantly stabilizes the otherwise very unstable semiquinone state, which accumulates over the course of reductive titrations with sodium dithionite. Furthermore, reduction of both EtfABs depleted of their electron-transferring FAD by NADH was monophasic with a hyperbolic dependence of reaction rate on the concentration of NADH. On the other hand, NADH reduction of the replete proteins containing the electron-transferring FAD was multiphasic, consisting of a fast phase comparable to that seen with the depleted proteins followed by an intermediate phase that involves significant accumulation of FAD⋅⁻, again reflecting uncrossing of the half-potentials of the bifurcating FAD. This is then followed by a slow phase that represents the slow reduction of the electron-transferring FAD to FADH⁻, with reduction of the now fully reoxidized bifurcating FAD by a second equivalent of NADH. We suggest that the crossing and uncrossing of the reduction half-potentials of the bifurcating FAD is due to specific conformational changes that have been structurally characterized.     

Detection and isolation of nuclear haplotypes by PCR-SSCP

SSCP (single-strand conformational polymorphism) is used widely in the field of human biomedicine, but its potential as a population genetics tool for the recovery of nuclear gene genealogies remains to be realized. We describe and illustrate a use for SSCP in the physical isolation of nuclear haplotypes that circumvents several difficulties associated with more conventional cloning procedures. The DNA sequence can be determined directly from the isolated haplotypes and used for phylogenetic inference. SSCP provides a convenient first step toward generating nuclear genealogies for population studies.