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A note to the reader

This journey in the collaborative publishing has started with the unreasonable request from a well-known publisher to make us pay 20,000 euros for an open access book that we (the editors), would have had to handle from A to Z (choose the chapters, find the authors, get the contracts signed, format the manuscript etc ...). It did not seem right, so we asked the colleagues that already had shown interest in writing a chapter for our book, to trust us. They did, and with the help of the HAL team and Christine Bibal, and some knowledge of LaTeX, here we are. Proud to present you our collective effort, licensed under CC BY-NC-ND 4.0.

Enjoy it freely.


Molecular phylogenetics was born in the middle of the 20th century, when the advent of protein and DNA sequencing offered a novel way to study the evolutionary relationships between living organisms. The first 50 years of the discipline can be seen as a long quest for resolving power. The goal – reconstructing the tree of life – seemed to be unreachable, the methods were heavily debated, and the data limiting. Maybe for these reasons, even the relevance of the whole approach was repeatedly questioned, as part of the so-called molecules versus morphology debate. Controversies often crystalized around long-standing conundrums, such as the origin of land plants, the diversification of placental mammals, or the prokaryote/eukaryote divide. Some of these questions were resolved as gene and species samples increased in size. Over the years, molecular phylogenetics has gradually evolved from a brilliant, revolutionary idea to a mature research field centred on the problem of reliably building trees.

This logical progression was abruptly interrupted in the late 2000s. High-throughput sequencing arose and the field suddenly moved into something entirely different. Access to genome-scale data profoundly reshaped the methodological challenges, while opening an amazing range of new application perspectives. Phylogenetics left the realm of systematics to occupy a central place in one of the most exciting research fields of this century – genomics. This is what this book is about: how we do trees, and what we do with trees, in the current phylogenomic era.

One obvious, practical consequence of the transition to genome-scale data is that the most widely used tree-building methods, which are based on probabilistic models of sequence evolution, require intensive algorithmic optimization to be applicable to current datasets. This problem is considered in Part 1 of the book, which includes a general introduction to Markov models (Chapter 1.1) and a detailed description of how to optimally design and implement Maximum Likelihood (Chapter 1.2) and Bayesian (Chapter 1.4) phylogenetic inference methods. The importance of the computational aspects of modern phylogenomics is such that efficient software development is a major activity of numerous research groups in the field. We acknowledge this and have included seven "How to" chapters presenting recent updates of major phylogenomic tools – RAxML (Chapter 1.3), PhyloBayes (Chapter 1.5), MACSE (Chapter 2.3), Bgee (Chapter 4.3), RevBayes (Chapter 5.2), Beagle (Chapter 5.4), and BPP (Chapter 5.6).

Genome-scale data sets are so large that statistical power, which had been the main limiting factor of phylogenetic inference during previous decades, is no longer a major issue. Massive data sets instead tend to amplify the signal they deliver – be it biological or artefactual – so that bias and inconsistency, instead of sampling variance, are the main problems with phylogenetic inference in the genomic era. Part 2 covers the issues of data  quality and model adequacy in phylogenomics. Chapter 2.1 provides an overview of current practice and makes recommendations on how to avoid the more common biases. Two chapters review the challenges and limitations of two key steps of phylogenomic analysis pipelines, sequence alignment (Chapter 2.2) and orthology prediction (Chapter 2.4), which largely determine the reliability of downstream inferences. The performance of tree building methods is also the subject of Chapter 2.5, in which a new approach is introduced to assess the quality of gene trees based on their ability to correctly predict ancestral gene order.

Analyses of multiple genes typically recover multiple, distinct trees. Maybe the biggest conceptual advance induced by the phylogenetic to phylogenomic transition is the suggestion that one should not simply aim to reconstruct “the” species tree, but rather to be prepared to make sense of forests of gene trees. Chapter 3.1 reviews the numerous reasons why gene trees can differ from each other and from the species tree, and what the implications are for phylogenetic inference. Chapter 3.2 focuses on gene trees/species trees reconciliation methods that account for gene duplication/loss and horizontal gene transfer among lineages. Incomplete lineage sorting is another major source of phylogenetic incongruence among loci, which recently gained attention and is covered by Chapter 3.3. Chapter 3.4 concludes this part by taking a user’s perspective and examining the pros and cons of concatenation versus separate analysis of gene sequence alignments.

Modern genomics is comparative and phylogenetic methods are key to a wide range of questions and analyses relevant to the study of molecular evolution. This is covered by Part 4. We argue that genome annotation, either structural or functional, can only be properly achieved in a phylogenetic context. Chapters 4.1 and 4.2 review the power of these approaches and their connections with the study of gene function. Molecular substitution rates play a key role in our understanding of the prevalence of nearly neutral versus adaptive molecular evolution, and the influence of species traits on genome dynamics (Chapter 4.4). The analysis of substitution rates, and particularly the detection of positive selection, requires sophisticated methods and models of coding sequence evolution (Chapter 4.5). Phylogenomics also offers a unique opportunity to explore evolutionary convergence at a molecular level, thus addressing the long-standing question of predictability versus contingency in evolution (Chapter 4.6).

The development of phylogenomics, as reviewed in Parts 1 through 4, has resulted in a powerful conceptual and methodological corpus, which is often reused for addressing problems of interest to biologists from other fields. Part 5 illustrates this application potential via three selected examples. Chapter 5.1 addresses the link between phylogenomics and palaeontology; i.e., how to optimally combine molecular and fossil data for estimating divergence times. Chapter 5.3 emphasizes the importance of the phylogenomic approach in virology and its potential to trace the origin and spread of infectious diseases in space and time. Finally, Chapter 5.5 recalls why phylogenomic methods and the multi-species coalescent model are key in addressing the problem of species delimitation – one of the major goals of taxonomy.

It is hard to predict where phylogenomics as a discipline will stand in even 10 years. Maybe a novel technological revolution will bring it to yet another level? We strongly believe, however, that tree thinking will remain pivotal in the treatment and interpretation of the deluge of genomic data to come. Perhaps a prefiguration of the future of our field is provided by the daily monitoring of the current Covid-19 outbreak via the phylogenetic analysis of coronavirus genomic data in quasi real time – a topic of major societal importance, contemporary to the publication of this book, in which phylogenomics is instrumental in helping to fight disease.

The digital version of the book, and of its individual chapters, are accessible for free and are distributed under licensed under a Creative Commons Attribution-NonCommercial- NoDerivatives 4.0 International license (CC BY-NC-ND 4.0). Hard copies can be printed on demand and profits, if any, will be directly re-invested in academia. The book was entirely designed, written, edited and distributed without the services of a professional publisher. The editors would like to thank all the authors for their tremendous contributions and enthusiastic participation to this collective effort. We are grateful to David Manley, Christine Bibal and the HAL platform for their help in editing/distributing this book.  

The scientific publishers

Celine Scornavacca, Frédéric Delsuc, Nicolas Galtier

A book completely handled by researchers.

No publisher has been paid.



Université de Montepellier CNRS    Inria

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