DNA Ligases: Progress and Prospects

DNA ligases seal 5′-PO₄ and 3′-OH polynucleotide ends via three nucleotidyl transfer steps involving ligase-adenylate and DNA-adenylate intermediates. DNA ligases are essential guardians of genomic integrity, and ligase dysfunction underlies human genetic disease syndromes. Crystal structures of DNA ligases bound to nucleotide and nucleic acid substrates have illuminated how ligase reaction chemistry is catalyzed, how ligases recognize damaged DNA ends, and how protein domain movements and active-site remodeling are used to choreograph the end-joining pathway. Although a shared feature of DNA ligases is their envelopment of the nicked duplex as a C-shaped protein clamp, they accomplish this feat by using remarkably different accessory structural modules and domain topologies. As structural, biochemical, and phylogenetic insights coalesce, we can expect advances on several fronts, including (i) pharmacological targeting of ligases for antibacterial and anticancer therapies and (ii) the discovery and design of new strand-sealing enzymes with unique substrate specificities.     

Depicting the Tree of Life: the Philosophical and Historical Roots of Evolutionary Tree Diagrams

It is a popularly held view that Darwin was the first author to draw a phylogenetic tree diagram. However, as is the case with most popular beliefs, this one also does not hold true. Firstly, Darwin never called his diagram of common descent a tree. Secondly, even before Darwin, tree diagrams were used by a variety of philosophical, religious, and secular scholars to depict phenomena such as “logical relationships,” “affiliations,” “genealogical descent,” “affinity,” and “historical relatedness” between the elements portrayed on the tree. Moreover, historically, tree diagrams themselves can be grouped into a larger class of diagrams that were drawn to depict natural and/or divine order in the world. In this paper, we trace the historical roots and cultural meanings of these tree diagrams. It will be demonstrated that tree diagrams as we know them are the outgrowth of ancient philosophical attempts to find the “true order” of the world, and to map the world “as it is” (ontologically), according to its true essence. This philosophical idea would begin a fascinating journey throughout Western European history. It lies at the foundation of the famous “scala naturae,” as well as religious and secular genealogical thinking, especially in regard to divine, familial (kinship), and linguistic pedigrees that were often depicted by tree images. These scala naturae would fuse with genealogical, pedigree thinking, and the trees that were the result of this blend would, from the nineteenth century onward, also include the element of time. The recognition of time would eventually lead to the recognition of evolution as a fact of nature, and subsequently, tree iconographies would come to represent exclusively the evolutionary descent of species.     

生命条形码与生命之树

生命条形码和生命之树的研究与应用在近十年内备受关注,成为生命科学研究领域的两个热点。本文综述了生命条形码和生命之树的概念来源、研究现状、面临问题与解决方案,并对其发展前景进行了展望。生命之树概念的形成有着悠久的历史渊源,DNA条形码的提出和实施则只有十年的历史,两者均得益于测序技术和生物信息技术的蓬勃发展;但两者的目的不同,生命条形码技术旨在实现对物种的快速鉴定,而生命之树研究的主要目的则是重建生命世界的起源和进化历史以及各生物类群之间的亲缘关系,因此应根据两者不同的目标任务而采取相应的发展思路和顶层设计。本文针对目前生命条形码和生命之树研究领域遇到的瓶颈和问题进行了阐述,并提出了相应的解决方案。最后,作者建议我国学者抓住机遇．与多个领域的学者和工程技术人员广泛合作,推动DNA条形码鉴定技术和生命之树理论研究的快速发展。     

Synergy of Energy and Semiosis: Cooperation Climbs the Tree of Life

The course of biological evolution is regarded by many authors as an ascending path toward higher levels of variety, complexity and integration. There are similar but partly conflicting accounts of the nature and causes of this ascending course. With the aim of reaching a unified conception I start by summarily reviewing three notable examples. These are, in their latest presentations, those of Hoffmeyer and Stjernfelt 2015, Szathmáry 2015, and Lane 2015a. Comparison of their commonalities and divergences, combined with further reflections, leads to the following views: 1) cooperation (synergy) between preexistent traits and processes is the primary determinant in the emergence of evolutionary novelty; 2) cooperation is a triadic relation similar to semiosis (while semiosis is a particular form of cooperation); 3) regulation, the key element of both metabolism and replication, results from the cooperation of energetic and semiotic causation; 4) conceptual generalization (as in scientific reasoning) and concrete generalization (as in biological evolution) are fruits of cooperation. Conceptual generalizations spring from the cooperation of ideas. I believe these realizations supply essential elements for a unified view of the ascent of biological evolution towards higher levels of organization. Some of these conceptions are also applicable to similar ascending trajectories through the stages of cultural and technological evolution.     

Calibrating the Tree of Life: fossils, molecules and evolutionary timescales

Background

Molecular dating has gained ever-increasing interest since the molecular clock hypothesis was proposed in the 1960s. Molecular dating provides detailed temporal frameworks for divergence events in phylogenetic trees, allowing diverse evolutionary questions to be addressed. The key aspect of the molecular clock hypothesis, namely that differences in DNA or protein sequence between two species are proportional to the time elapsed since they diverged, was soon shown to be untenable. Other approaches were proposed to take into account rate heterogeneity among lineages, but the calibration process, by which relative times are transformed into absolute ages, has received little attention until recently. New methods have now been proposed to resolve potential sources of error associated with the calibration of phylogenetic trees, particularly those involving use of the fossil record.

Scope and Conclusions

The use of the fossil record as a source of independent information in the calibration process is the main focus of this paper; other sources of calibration information are also discussed. Particularly error-prone aspects of fossil calibration are identified, such as fossil dating, the phylogenetic placement of the fossil and the incompleteness of the fossil record. Methods proposed to tackle one or more of these potential error sources are discussed (e.g. fossil cross-validation, prior distribution of calibration points and confidence intervals on the fossil record). In conclusion, the fossil record remains the most reliable source of information for the calibration of phylogenetic trees, although associated assumptions and potential bias must be taken into account.     

The Tree versus the Forest: The Fungal Tree of Life and the Topological Diversity within the Yeast Phylome

A recurrent topic in phylogenomics is the combination of various sequence alignments to reconstruct a tree that describes the evolutionary relationships within a group of species. However, such approach has been criticized for not being able to properly represent the topological diversity found among gene trees. To evaluate the representativeness of species trees based on concatenated alignments, we reconstruct several fungal species trees and compare them with the complete collection of phylogenies of genes encoded in the Saccharomyces cerevisiae genome. We found that, despite high levels of among-gene topological variation, the species trees do represent widely supported phylogenetic relationships. Most topological discrepancies between gene and species trees are concentrated in certain conflicting nodes. We propose to map such information on the species tree so that it accounts for the levels of congruence across the genome. We identified the lack of sufficient accuracy of current alignment and phylogenetic methods as an important source for the topological diversity encountered among gene trees. Finally, we discuss the implications of the high levels of topological variation for phylogeny-based orthology prediction strategies.     

Mapping of Bancroftian Filariasis in Cameroon: Prospects for Elimination

BackgroundLymphatic filariasis (LF) is one of the most debilitating neglected tropical diseases (NTDs). It still presents as an important public health problem in many countries in the tropics. In Cameroon, where many NTDs are endemic, only scant data describing the situation regarding LF epidemiology was available. The aim of this study was to describe the current situation regarding LF infection in Cameroon, and to map this infection and accurately delineate areas where mass drug administration (MDA) was required.MethodologyThe endemicity status and distribution of LF was assessed in eight of the ten Regions of Cameroon by a rapid-format card test for detection of W. bancrofti antigen (immunochromatographic test, ICT). The baseline data required to monitor the effectiveness of MDA was collected by assessing microfilariaemia in nocturnal calibrated thick blood smears in sentinel sites selected in the health districts where ICT positivity rate was ≥ 1%.Conclusion/significanceICT card test results showed that LF was endemic in all the Regions and in about 90% of the health districts surveyed. All of these health districts qualified for MDA (i.e. ICT positivity rate ≥ 1%). Microfilariaemia data collected as part of this study provided the national program with baseline data (sentinel sites) necessary to measure the impact of MDA on the endemicity level and transmission of LF important for the 2020 deadline for global elimination.     

Assembling the Fungal Tree of Life: constructing the structural and biochemical database

A major goal of the Assembling the Fungal Tree of Life project is to create a searchable database of selected ultrastructural and biochemical characters from published and new data for use in phylogenetic and other analyses. While developing this database such issues as evaluating specimen fixation quality in published micrographs, organizing data to accommodate characters that were dependent on location and developmental stage, and requiring accountability of data contributors were addressed. Character states for three traits, septal pore apparatus, nuclear division and spindle pole body cycle, are illustrated, and character states are resolved with maximum parsimony and plotted on a summary cladogram of known phylogenetic relationships of the Fungi. The analysis illustrates the inherent phylogenetic signal of these characters, the paucity of comparable characters and character states in subcellular studies and the challenges in establishing a comprehensive structural and biochemical database of the Fungi.     

生命之树与进化模式:导言

One and half centuries ago, Charles Darwin (1859) presented overwhelming evidence and argued that all life on the earth shared common descent, and "from so simple a beginning endless forms most beautiful and most wonderful have been, and are being evolved". Ernst Haeckel (1886) and several of his contemporaries attempted to trace the pattern of descent among all extant and extinct forms in what Darwin referred to as "the great Tree of Life". Ever since then, systematists and evolutionary biologists have been exploring morphological, cytogenetic, chemical, developmental and molecular characters, and actively developing theories and methods to infer phylogenetic relationships among organisms from these characters. This endeavor has been especially stimulated by the rise of molecular biology and the emergence of computer science over the past 50 years. At the beginning of the 21st century, we are presented with an unprecedented opportunity to reconstruct the entire Tree of Life, and further, to study evolutionary processes and mechanisms in the context of a robust phylogenetic framework.     

Rocks and clocks: calibrating the Tree of Life using fossils and molecules

A great tradition in macroevolution and systematics has been the ritual squabbling between palaeontologists and molecular biologists. But, because both sides were talking past each other, they could never agree. Practitioners in both fields should play to their strengths and work together: palaeontologists can provide minimum constraints on branching points in the Tree of Life with considerable precision, and estimate the extent of unrecorded prehistory. Molecular tree analysts have remarkable modelling tools in their armoury to convert multiple minimum age constraints into meaningful dated trees. As we discuss here, work should now focus on establishing reasonable, dated trees that satisfy rigorous assessment of the available fossils and careful consideration of molecular tree methods: rocks and clocks together are an unbeatable combination. Reliably dated trees provide, for the first time, the opportunity to explore wider questions in macroevolution.     

Space, time, form: viewing the Tree of Life

There are numerous ways to display a phylogenetic tree, which is reflected in the diversity of software tools available to phylogenetists. Displaying very large trees continues to be a challenge, made ever harder as increasing computing power enables researchers to construct ever-larger trees. At the same time, computing technology is enabling novel visualisations, ranging from geophylogenies embedded on digital globes to touch-screen interfaces that enable greater interaction with evolutionary trees. In this review, I survey recent developments in phylogenetic visualisation, highlighting successful (and less successful) approaches and sketching some future directions.