Statistical phylogeography

While studies of phylogeography and speciation in the past have largely focused on the documentation or detection of significant patterns of population genetic structure, the emerging field of statistical phylogeography aims to infer the history and processes underlying that structure, and to provide objective, rather than ad hoc explanations. Methods for parameter estimation are now commonly used to make inferences about demographic past. Although these approaches are well developed statistically, they typically pay little attention to geographical history. In contrast, methods that seek to reconstruct phylogeographic history are able to consider many alternative geographical scenarios, but are primarily nonstatistical, making inferences about particular biological processes without explicit reference to stochastically derived expectations. We advocate the merging of these two traditions so that statistical phylogeographic methods can provide an accurate representation of the past, consider a diverse array of processes, and yet yield a statistical estimate of that history. We discuss various conceptual issues associated with statistical phylogeographic inferences, considering especially the stochasticity of population genetic processes and assessing the confidence of phylogeographic conclusions. To this end, we present some empirical examples that utilize a statistical phylogeographic approach, and then by contrasting results from a coalescent-based approach to those from Templeton's nested cladistic analysis (NCA), we illustrate the importance of assessing error. Because NCA does not assess error in its inferences about historical processes or contemporary gene flow, we performed a small-scale study using simulated data to examine how our conclusions might be affected by such unconsidered errors. NCA did not identify the processes used to simulate the data, confusing among deterministic processes and the stochastic sorting of gene lineages. There is as yet insufficient justification of NCA's ability to accurately infer or distinguish among alternative processes. We close with a discussion of some unresolved problems of current statistical phylogeographic methods to propose areas in need of future development.     

Investigating the evolutionary history of the Pacific Northwest mesic forest ecosystem: hypothesis testing within a comparative phylogeographic framework

We examine the evolution of mesic forest ecosystems in the Pacific Northwest of North America using a statistical phylogeography approach in four animal and two plant lineages. Three a priori hypotheses, which explain the disjunction in the mesic forest ecosystem with either recent dispersal or ancient vicariance, are tested with phylogenetic and coalescent methods. We find strong support in three amphibian lineages (Ascaphus spp., and Dicampton spp., and Plethodon vandykei and P. idahoensis) for deep divergence between coastal and inland populations, as predicted by the ancient vicariance hypothesis. Unlike the amphibians, the disjunction in other Pacific Northwest lineages is likely due to recent dispersal along a northern route. Topological and population divergence tests support the northern dispersal hypothesis in the water vole (Microtus richardsoni) and northern dispersal has some support in both the dusky willow (Salix melanopsis) and whitebark pine (Pinus albicaulis). These analyses demonstrate that genetic data sampled from across an ecosystem can provide insight into the evolution of ecological communities and suggest that the advantages of a statistical phylogeographic approach are most pronounced in comparisons across multiple taxa in a particular ecosystem. Genetic patterns in organisms as diverse as willows and salamanders can be used to test general regional hypotheses, providing a consistent metric for comparison among members of an ecosystem with disparate life-history traits.     

Integrating GIS-based environmental data into evolutionary biology

Many evolutionary processes are influenced by environmental variation over space and time, including genetic divergence among populations, speciation and evolutionary change in morphology, physiology and behaviour. Yet, evolutionary biologists have generally not taken advantage of the extensive environmental data available from geographic information systems (GIS). For example, studies of phylogeography, speciation and character evolution often ignore or use only crude proxies for environmental variation (e.g. latitude and distance between populations). Here, we describe how the integration of GIS-based environmental data, along with new spatial tools, can transform evolutionary studies and reveal new insights into the ecological causes of evolutionary patterns.     

The burgeoning field of statistical phylogeography

In the newly emerging field of statistical phylogeography, consideration of the stochastic nature of genetic processes and explicit reference to theoretical expectations under various models has dramatically transformed how historical processes are studied. Rather than being restricted to ad hoc explanations for observed patterns of genetic variation, assessments about the underlying evolutionary processes are now based on statistical tests of various hypotheses, as well as estimates of the parameters specified by the models. A wide range of demographical and biogeographical processes can be accommodated by these new analytical approaches, providing biologically more realistic models. Because of these advances, statistical phylogeography can provide unprecedented insights about a species' history, including decisive information about the factors that shape patterns of genetic variation, species distributions, and speciation. However, to improve our understanding of such processes, a critical examination and appreciation of the inherent difficulties of historical inference and challenges specific to testing phylogeographical hypotheses are essential. As the field of statistical phylogeography continues to take shape many difficulties have been resolved. Nonetheless, careful attention to the complexities of testing historical hypotheses and further theoretical developments are essential to improving the accuracy of our conclusions about a species' history.     

Environmental DNA phylogeography: Successful reconstruction of phylogeographic patterns of multiple fish species from cups of water

Phylogeography is an integrative field of science linking micro- and macro-evolutionary processes, contributing to the inference of vicariance, dispersal, speciation, and other population-level processes. Phylogeographic surveys usually require considerable effort and time to obtain numerous samples from many geographical sites covering the distribution range of target species; this associated high cost limits their application. Recently, environmental DNA (eDNA) analysis has been useful not only for detecting species but also for assessing genetic diversity; hence, there has been growing interest in its application to phylogeography. As the first step of eDNA-based phylogeography, we examined (1) data screening procedures suitable for phylogeography and (2) whether the results obtained from eDNA analysis accurately reflect known phylogeographic patterns. For these purposes, we performed quantitative eDNA metabarcoding using group-specific primer sets in five freshwater fish species belonging to two taxonomic groups from a total of 94 water samples collected from western Japan. As a result, three-step data screening based on the DNA copy number of each haplotype detected successfully eliminated suspected false positive haplotypes. Furthermore, eDNA analysis could almost perfectly reconstruct the phylogenetic and phylogeographic patterns obtained for all target species with the conventional method. Despite existing limitations and future challenges, eDNA-based phylogeography can significantly reduce survey time and effort and is applicable for simultaneous analysis of multiple species in single water samples. eDNA-based phylogeography has the potential to revolutionize phylogeography.     

Concept, design and implementation of a cardiovascular gene-centric 50 k SNP array for large-scale genomic association studies

A wealth of genetic associations for cardiovascular and metabolic phenotypes in humans has been accumulating over the last decade, in particular a large number of loci derived from recent genome wide association studies (GWAS). True complex disease-associated loci often exert modest effects, so their delineation currently requires integration of diverse phenotypic data from large studies to ensure robust meta-analyses. We have designed a gene-centric 50 K single nucleotide polymorphism (SNP) array to assess potentially relevant loci across a range of cardiovascular, metabolic and inflammatory syndromes. The array utilizes a "cosmopolitan" tagging approach to capture the genetic diversity across approximately 2,000 loci in populations represented in the HapMap and SeattleSNPs projects. The array content is informed by GWAS of vascular and inflammatory disease, expression quantitative trait loci implicated in atherosclerosis, pathway based approaches and comprehensive literature searching. The custom flexibility of the array platform facilitated interrogation of loci at differing stringencies, according to a gene prioritization strategy that allows saturation of high priority loci with a greater density of markers than the existing GWAS tools, particularly in African HapMap samples. We also demonstrate that the IBC array can be used to complement GWAS, increasing coverage in high priority CVD-related loci across all major HapMap populations. DNA from over 200,000 extensively phenotyped individuals will be genotyped with this array with a significant portion of the generated data being released into the academic domain facilitating in silico replication attempts, analyses of rare variants and cross-cohort meta-analyses in diverse populations. These datasets will also facilitate more robust secondary analyses, such as explorations with alternative genetic models, epistasis and gene-environment interactions.     

Twenty years of phylogeography: the state of the field and the challenges for the Southern Hemisphere

Phylogeography is a young, vigorous and integrative field of study that uses genetic data to understand the history of populations. This field has recently expanded into many areas of biology and also into several historical disciplines of Earth sciences. In this review, I present a numerical synthesis of the phylogeography literature based on an examination of over 3000 articles published during the first 20 years of the field (i.e. from 1987 to 2006). Information from several topics needed to evaluate the progress, tendencies and deficiencies of the field is summarized for 10 major groups of organisms and at a global scale. The topics include the geography of phylogeographic surveys, comparative nature of studies, temporal scales and major environments investigated, and genetic markers used. I also identify disparities in research productivity between the developing and the developed world, and propose ways to reduce some of the challenges faced by phylogeographers from less affluent countries. Phylogeography has experienced explosive growth in recent years fuelled by developments in DNA technology, theory and statistical analysis. I argue that the intellectual maturation of the field will eventually depend not only on these recent developments, but also on syntheses of comparative information across different regions of the globe. For this to become a reality, many empirical phylogeographic surveys in regions of the Southern Hemisphere (and in developing countries of the Northern Hemisphere) are needed. I expect the information and views presented here will assist in promoting international collaborative work in phylogeography and in guiding research efforts at both regional and global levels.     

分子系统地理学及其应用

分子系统地理学是20世纪70年代中期伴随着对线粒体DNA的认识而开始酝酿发展的,本文回顾了该学科自诞生以来的发展简史,阐述了其研究内容,着重从3个方面介绍了该领域在其它相关学科中的研究进展,总结了该学科存在的问题,并提出重点应解决的3个问题：1）将细胞器基因与遗传信息更为丰富的核基因相结合;2）合生理论在非平衡种群中的发展应用;3）提高对分化时间估计的精确性。     

Congruence, consensus, and the comparative phylogeography of codistributed species in California

Comparative phylogeography has emerged as a means of understanding the spatial patterns of genetic divergence of codistributed species. However, researchers are often frustrated because of the lack of appropriate statistical tests to assess concordancy of multiple phylogeographic trees. We develop a method for testing congruence across multiple species and synthesizing the data into a regional supertree. Nine phylogeographic data sets of species with different life histories and ecologies were statistically compared using maximum agreement subtrees (MAST) and showed a high degree of concordancy. A supertree combining the different phylogeographic trees was then computed using matrix representation with parsimony, and the groups defined by this supertree were tested against climatic data to investigate a potential mechanism driving divergence. Our data suggest that species and genetic lineages in California are shaped by climatic regimes. The supertree method in combination with MAST represents a new approach to test congruence hypotheses and detect common geographic signals in comparative phylogeography.     

Distinguishing between hot-spots and melting-pots of genetic diversity using haplotype connectivity

We introduce a method to help identify how the genetic diversity of a species within a geographic region might have arisen. This problem appears, for example, in the context of identifying refugia in phylogeography, and in the conservation of biodiversity where it is a factor in nature reserve selection. Complementing current methods for measuring genetic diversity, we analyze pairwise distances between the haplotypes of a species found in a geographic region and derive a quantity, called haplotype connectivity, that aims to capture how divergent the haplotypes are relative to one another. We propose using haplotype connectivity to indicate whether, for geographic regions that harbor a highly diverse collection of haplotypes, diversity evolved inside a region over a long period of time (a "hot-spot") or is the result of a more recent mixture (a "melting-pot"). We describe how the haplotype connectivity for a collection of haplotypes can be computed efficiently and briefly discuss some related optimization problems that arise in this context. We illustrate the applicability of our method using two previously published data sets of a species of beetle from the genus Brachyderes and a species of tree from the genus Pinus.     

Genetic diversity in the European wild boar Sus scrofa: phylogeography,population structure and wild x domestic hybridization

• 1 Despite the vast literature on genetic variation in the domestic pig Sus scrofa, little is known about genetic differentiation in wild boar populations.
• 2 Here we present an up‐to‐date review of published data on the past and recent history of the European wild boar, its genetic diversity and the spatial distribution of genetic variation throughout the continent.
• 3 The phylogeography of the species seems to be shaped mostly by past large‐scale events (like postglacial recolonization) rather than by more recent human manipulation. Genetic differentiation is observed both on a continental and a regional scale, and non‐intuitive barriers to gene flow occur.
• 4 From an indirect estimate, hybridization between wild boar and domestic pigs is seemingly a minor source of genetic variation for wild boar populations, yet risks are still linked to the release of captive hybrids in some areas.
• 5 Finally, we present future perspectives concerning the development of powerful molecular tools and their possible application to the study and management of this species.

     

Analyses of genetic ancestry enable key insights for molecular ecology

Gene flow and recombination in admixed populations produce genomes that are mosaic combinations of chromosome segments inherited from different source populations, that is, chromosome segments with different genetic ancestries. The statistical problem of estimating genetic ancestry from DNA sequence data has been widely studied, and analyses of genetic ancestry have facilitated research in molecular ecology and ecological genetics. In this review, we describe and compare different model‐based statistical methods used to infer genetic ancestry. We describe the conceptual and mathematical structure of these models and highlight some of their key differences and shared features. We then discuss recent empirical studies that use estimates of genetic ancestry to analyse population histories, the nature and genetic basis of species boundaries, and the genetic architecture of traits. These diverse studies demonstrate the breadth of applications that rely on genetic ancestry estimates and typify the genomics‐enabled research that is becoming increasingly common in molecular ecology. We conclude by identifying key research areas where future studies might further advance this field.     

Genetic Landscapes GIS Toolbox: tools to map patterns of genetic divergence and diversity

The Landscape Genetics GIS Toolbox contains tools that run in the Geographic Information System software, ArcGIS^®, to map genetic landscapes and to summarize multiple genetic landscapes as average and variance surfaces. These tools can be used to visualize the distribution of genetic diversity across geographic space and to study associations between patterns of genetic diversity and geographic features or other geo‐referenced environmental data sets. Together, these tools create genetic landscape surfaces directly from tables containing genetic distance or diversity data and sample location coordinates, greatly reducing the complexity of building and analyzing these raster surfaces in a Geographic Information System.     

Genetic engineering approaches to improve posttranslational modification of biopharmaceuticals in different production platforms

The number of approved biopharmaceuticals, where product quality attributes remain of major importance, is increasing steadily. Within the available variety of expression hosts, the production of biopharmaceuticals faces diverse limitations with respect to posttranslational modifications (PTM), while different biopharmaceuticals demand different forms and specifications of PTMs for proper functionality. With the growing toolbox of genetic engineering technologies, it is now possible to address general as well as host- or biopharmaceutical-specific product quality obstacles. In this review, we present diverse expression systems derived from mammalians, bacteria, yeast, plants, and insects as well as available genetic engineering tools. We focus on genes for knockout/knockdown and overexpression for meaningful approaches to improve biopharmaceutical PTMs and discuss their applicability as well as future trends in the field.     

Putting the "landscape" in landscape genetics

Landscape genetics has emerged as a new research area that integrates population genetics, landscape ecology and spatial statistics. Researchers in this field can combine the high resolution of genetic markers with spatial data and a variety of statistical methods to evaluate the role that landscape variables play in shaping genetic diversity and population structure. While interest in this research area is growing rapidly, our ability to fully utilize landscape data, test explicit hypotheses and truly integrate these diverse disciplines has lagged behind. Part of the current challenge in the development of the field of landscape genetics is bridging the communication and knowledge gap between these highly specific and technical disciplines. The goal of this review is to help bridge this gap by exposing geneticists to terminology, sampling methods and analysis techniques widely used in landscape ecology and spatial statistics but rarely addressed in the genetics literature. We offer a definition for the term "landscape genetics", provide an overview of the landscape genetics literature, give guidelines for appropriate sampling design and useful analysis techniques, and discuss future directions in the field. We hope, this review will stimulate increased dialog and enhance interdisciplinary collaborations advancing this exciting new field.     

Single-cell microbiology: tools, technologies, and applications.

The field of microbiology has traditionally been concerned with and focused on studies at the population level. Information on how cells respond to their environment, interact with each other, or undergo complex processes such as cellular differentiation or gene expression has been obtained mostly by inference from population-level data. Individual microorganisms, even those in supposedly "clonal" populations, may differ widely from each other in terms of their genetic composition, physiology, biochemistry, or behavior. This genetic and phenotypic heterogeneity has important practical consequences for a number of human interests, including antibiotic or biocide resistance, the productivity and stability of industrial fermentations, the efficacy of food preservatives, and the potential of pathogens to cause disease. New appreciation of the importance of cellular heterogeneity, coupled with recent advances in technology, has driven the development of new tools and techniques for the study of individual microbial cells. Because observations made at the single-cell level are not subject to the "averaging" effects characteristic of bulk-phase, population-level methods, they offer the unique capacity to observe discrete microbiological phenomena unavailable using traditional approaches. As a result, scientists have been able to characterize microorganisms, their activities, and their interactions at unprecedented levels of detail.     

When GIS zooms in: spatio-genetic maps of multipaternity in<Emphasis Type="Italic"> Armadillidium vulgare</Emphasis>

Geographic information system (GIS) tools are designed to illustrate, analyse and integrate geographic or spatial data, usually on a macroscopic scale. By contrast, genetic tools focus on a microscopic scale. Because in reality, landscapes have no predefined scale, our original study aims to develop a new approach, combining both cartographic and genetic approaches to explore microscopic landscapes. For this, we focused on Armadillidium vulgare, a terrestrial isopod model in which evolutionary pressures imposed by terrestrial life have led to the development of internal fertilisation and, consequently, to associated physiological changes. Among these, the emergence of internal receptacles, found in many taxa ranging from mammals to arthropods, allowed females to store sperm from several partners, enabling multipaternity. Among arthropods, terrestrial isopods like the polygynandrous A. vulgare present a female structure, the marsupium, in which fertilised eggs migrate and develop into mancae (larval stage). To test our innovative combined approach, we proposed different males to four independent females, and at the end of incubation in the marsupium, we mapped (using GIS methods) and genotyped (using 12 microsatellite markers) all the incubated mancae. This methodology permitted to obtain spatio-genetic maps describing heterozygosity and spatial distribution of mancae and of multipaternity within the marsupial landscape. We discussed the interest of this kind of multidisciplinary approach which could improve in this case our understanding of sexual selection mechanisms in this terrestrial crustacean. Beyond the interesting model-focused insights, the main challenge of this study was the transfer of GIS techniques to a microscopic scale and our results appear so as pioneers rendering GIS tools available for studies involving imagery whatever their study scale.     

Phylogeography: spanning the ecology‐evolution continuum

Synthesis of ecological and evolutionary concepts and tools has led to improved understanding of how diversification, dispersal, community assembly, long‐term coexistence and extinction shape patterns of biological diversity. Phylogeography, with its focus on Quaternary interactions within and between populations, can help elucidate the processes acting between the evolutionary time‐scales on which species arise and the ecological time‐scales on which members of an assemblage interact with each other and their environment. Still, it has yet to be widely incorporated in that synthesis. Here, we highlight three areas where integration of phylogeography with ecological and evolutionary approaches can provide new insights into key questions. First, phylogeography can help clarify the roles of isolation, niche conservatism and environmental stability in generating patterns of alpha‐ and beta‐diversity. Second, phylogeography can help isolate the effects of Quaternary dispersal limitation from other factors driving community assembly and spatial turnover. Third, phylogeography can help identify key processes leading to and resulting from extinction events, including the population dynamics of species range reduction and its effects on the strength and temporal flexibility of networks of species interactions. We conclude with an outlook on the data‐gathering protocols necessary for this collaborative, interdisciplinary research agenda.     

The Relative Numbers of Different Genes in Exponential Microbial Cultures

It is shown that the results of the marker frequency analysis of Sueoka and Yoshikawa (1965) can be derived as very good approximations from a model where the rigid assumptions of their analysis are relaxed to take into account statistical variations in the timing of cell events. It is further shown that the expression for the amount of DNA per cell can be approximated by an elementary exponential function of the growth rate, and this result facilitates genetic mapping by DNA hybridization techniques. An analysis of recent data on gene frequencies in Escherichia coli corroborates a model of symmetric, bidirectional chromosome replication with a replication time of approximately thirty minutes.