Johannes Jaeger

University of Vienna | UniWien · Dept of Philosophy

What is the prospect of developing artificial general intelligence (AGI)? I investigate this question by systematically comparing living and algorithmic systems, with a special focus on the notion of "agency." There are three fundamental differences to consider: (1) Living systems are autopoietic, that is, self-manufacturing, and therefore able to...

The origin of RNA interference (RNAi) is usually explained by a defense-based hypothesis, in which RNAi evolved as a defense against transposable elements (TEs) and RNA viruses and was already present in the last eukaryotic common ancestor (LECA). However, since RNA antisense regulation and double-stranded RNAs (dsRNAs) are ancient and widespread p...

At first sight, the empirical study of ontogenesis and the theoretical study of organismal agency seem to have little in common. In this chapter, we discuss why this initial impression is incorrect. First of all, ontogenesis and agency are indirectly connected at the level of the whole organism, since they are co-dependent on the peculiar organizat...

Humanity is currently confronted with a series of profound existential crises. Beneath it all lies a crisis of meaning, of being able to make sense of the world. If we are to overcome this situation, we need robust scientific knowledge of the world and our place within it. However, science is facing a number of serious challenges to meet these need...

Artificial intelligence has made tremendous advances since its inception about seventy years ago. Self-driving cars, programs beating experts at complex games, and smart robots capable of assisting people that need care are just some among the successful examples of machine intelligence. This kind of progress might entice us to envision a society p...

Artificial intelligence has made tremendous advances since its inception about seventy years ago. Self-driving cars, programs beating experts at complex games, and smart robots capable of assisting people that need care are just some among the successful examples of machine intelligence. This kind of progress might entice us to envision a society p...

An organism’s phenotype can be thought of as consisting of a set of discrete traits, able to evolve relatively independently of each other. This implies that the developmental processes generating these traits—the underlying genotype-phenotype map—must also be functionally organised in a modular manner. The genotype-phenotype map lies at the heart...

Comparative biology builds up systematic knowledge of the diversity of life, across evolutionary lineages and levels of organization, starting with evidence from a sparse sample of model organisms. In developmental biology, a key obstacle to the growth of comparative approaches is that the concept of homology is not very well defined for levels of...

Modularity is an essential feature of any adaptive complex system. Phenotypic traits are modules in the sense that they have a distinguishable structure or function, which can vary (quasi-)independently from its context. Since all phenotypic traits are the product of some underlying regulatory dynamics, the generative processes that constitute the...

We present a progress report on our efforts to establish a new research program for evolutionary systems biology, based on reverse engineering and in silico evolution. The aim is a mechanistic understanding of the genotype-phenotype map and its evolution. Our review focuses on the case study of the gap gene network in dipteran insects (flies and mi...

This chapter examines the deep connections between biological organization, agency, and evolution by natural selection. Using Griesemer’s account of the re- producer, I argue that the basic unit of evolution is not a genetic replicator, but a complex hierarchical life cycle. Understanding the self-maintaining and self-proliferating properties of ev...

Modularity is an essential feature of any adaptive complex system. Phenotypic traits are modules in the sense that they have a distinguishable structure or function, which can vary (quasi-)independently from its context. Since all phenotypic traits are the product of some underlying regulatory dynamics, the generative processes that constitute the...

An organism’s phenotype can be thought of as consisting of a set of discrete traits, able to evolve relatively independently of each other. This implies that the developmental processes generating these traits—the underlying genotype-phenotype map—must also be functionally organised in a modular manner. The genotype-phenotype map lies at the heart...

Evolution does not act on particular stages in the life of an organism. Instead, it alters developmental processes and life cycles in response to environmental conditions to bring about phenotypic change. The structure of these processes determines evolvability, the capacity of organisms to adapt. These structures are intrinsically dynamic. The org...

This manuscript is a chapter in the book "Evolutionary Systems Biology: Advances, Questions, and Opportunities" to be published with Springer-Nature.

The logic of genetic discovery has changed little over time, but the focus of biology is shifting from simple genotype-phenotype relationships to complex metabolic, physiological, developmental , and behavioral traits. In light of this, we reexamine the traditional reductionist view of individual genes as privileged difference-making causes of phen...

Explanation in terms of gene regulatory networks (GRNs) has become standard practice in evolutionary developmental biology (evo-devo). In this paper, we argue that GRNs fail to provide a robust, mechanistic, and dynamic understanding of the developmental processes underlying the genotype-phenotype map. Explanations based on GRNs are limited by thre...

The existence of discrete phenotypic traits suggests that the complex regulatory processes which produce them are functionally modular. These processes are usually represented by networks. Only modular networks can be partitioned into intelligible subcircuits able to evolve relatively independently. Traditionally, functional modularity is approxima...

The authors, an artist, a mathematician and a biologist, describe their collaboration examining the potential of drawing to further the understanding of biological processes. As a case study, this article considers C.H. Waddington's powerful visual representation of the “epigenetic landscape,” whose purpose is to unify research in genetics, embryol...

There is much talk about information in biology. In developmental biology, this takes the form of "positional information," especially in the context of morphogen-based pattern formation. Unfortunately, the concept of "information" is rarely defined in any precise manner. Here, we provide two alternative interpretations of "positional information,"...

For us to understand complex regulatory networks and their evolution, they must be modular, at least to some degree. Only modular networks can be partitioned into tractable subcircuits, able to evolve without causing detrimental pleiotropic effects. Traditionally, functional modularity is approximated by detection of modularity in the regulatory st...

Gap genes are involved in segment determination during early development of the vinegar fly Drosophila melanogaster and other dipteran insects (flies, midges and mosquitoes). They are expressed in overlapping domains along the antero-posterior (A–P) axis of the blastoderm embryo. While gap domains cover the entire length of the A–P axis in Drosophi...

Cuticle preparations of late-stage RNA-depleted embryos for Ca-gt RNAi and Ca-tal RNAi

ELife digest For a single fertilized egg to become an animal with many millions of cells, complex networks of genes must control the different stages of development. These gene networks create all the patterns needed to form different parts of the body. Changes to these patterns can create new species, with different sizes, body shapes, colors and...

Insects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum, use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster, determine all segments simultaneously through a hierarchical cascade of gene...

Damped oscillator mechanism predicts high levels of Kr and Hb in the abdominal region upon hb overexpression. We use our model (A) and the static-Bcd model from [23] (B) to simulate 20 trajectories, with initial Hb concentrations ranging from 0 to 200 (arbitrary units). This mimics increasing levels of hb overexpression. Phase portraits are shown f...

Values of the parameters in the nonautonomous gap gene circuit model. Model equations are shown in the Materials and methods section. Values of promoter thresholds were fixed to −2.5 during optimization. (PDF)

Additional information on diffusion-less models and model fitting, plus a glossary of dynamical systems terms. (PDF)

The effect of Cad concentration on the geometry of the flow. Unfolded, two-dimensional projections of the Kr-Kni and Kni-Gt planes are shown, as in Fig 4C–4E in the main paper, for all time classes (C12 indicating the onset of cleavage cycle C13 at t = 0). A, B. Plots with colored arrows indicate flow in a simulation with WT levels of Cad (A) or Ca...

Rotating three-dimensional projection of the nonautonomous trajectories for every other nucleus between 53% and 71% A–P position. A static version of this graph is shown in Fig 2C of the main paper. Axes represent Kr (green), Kni (red), and Gt (blue) protein concentrations (in arbitrary units). Colored points on trajectories are marking their progr...

Canalizing properties of the gap gene damped oscillator. We simulate the nonautonomous diffusion-less circuit in the nucleus at 59% A–P position with Kni concentration fixed to zero (A, B), as in Fig 3A and 3B in the main manuscript, fixed to 10 (A′, B′) and fixed to 50 (A″, B″), and a set of initial conditions that are regularly distributed on the...

Spatiotemporal pattern of gt mRNA in wild-type versus cadmat mutants. Laterally aligned embryos are shown (anterior is to the left, dorsal on top), stained by enzymatic (colorimetric) in situ hybridization for gt (blue), and also the pair-rule gene eve (red), in the case of cadmat embryos. Embryos are shown at cleavage cycle 13 (C13), and cleavage...

Rotating three-dimensional projection of the time-variable phase portrait for the nucleus at 59% A–P position. A static version of this graph is shown in Fig 2B of the main paper. Axes represent Kr (green), Kni (red), and Gt (blue) protein concentrations (in arbitrary units). Hb is not present in this nucleus. Spiral sinks are represented by cylind...

Gap and maternal coordinate gene expression data used for model solution and fitting. This spreadsheet contains three parts: (1) gap gene data against which the model is fit; (2) initial values of Hb (maternal Hb expression). All other gap genes have zero concentrations at t = 0; (3) expression of maternal genes and terminal gap genes used as exter...

Gap genes are involved in segment determination during early development of the vinegar fly Drosophila melanogaster and other dipteran insects (flies, midges, and mosquitoes). They are expressed in overlapping domains along the antero-posterior (A–P) axis of the blastoderm embryo. While gap domains cover the entire length of the A–P axis in Drosoph...

Evolution of morphogenesis is generally associated with changes in genetic regulation. Here we report evidence indicating that dorsal closure, a conserved morphogenetic process in dipterans, evolved as the consequence of rearrangements in epithelial organization rather than signaling regulation. In Drosophila melanogaster , dorsal closure consists...

“While we do not necessarily need strictly hypothesis-driven investigation, thoughtful, curiosity-driven research is a must. If we continue the way we are currently going, we run the danger of ending up with massive mountains of big data that nobody can interpret. Systems biology should not reinforce this trend, but rather provide new ways for maki...

Insects determine their body segments in two different ways. Short-germband insects, such as the flour beetle Tribolium castaneum , use a molecular clock to establish segments sequentially. In contrast, long-germband insects, such as the vinegar fly Drosophila melanogaster , determine all segments simultaneously through a hierarchical cascade of ge...

Background Bone morphogenetic proteins (BMPs) are of central importance for dorsal–ventral (DV) axis specification. They are core components of a signalling cascade that includes the BMP ligand decapentaplegic (DPP) and its antagonist short gastrulation (SOG) in Drosophila melanogaster. These components are very ancient, with orthologs involved in...

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster. Gap genes are...

Dynamical systems concepts. (A) Features of phase space in autonomous dynamical systems. (B) Categorisation of transient, non-autonomous dynamics. (PNG)

The three most commonly observed patterning defects in fully non-autonomous diffusion-less gap gene circuits. Commonly observed defects in fully autonomous D. melanogaster gap gene circuits fitted to data without diffusion. Circuits showing any of these gross patterning defects were excluded from further analysis, even if their RMS score was low. A...

Values of the parameters in the non-autonomous gap gene circuit model. Model equations are shown in the Models and Methods section. (PDF)

Pattern formation during development is a highly dynamic process. In spite of this, few experimental and modelling approaches take into account the explicit time-dependence of the rules governing regulatory systems. We address this problem by studying dynamic morphogen interpretation by the gap gene network in Drosophila melanogaster . Gap genes ar...

Developmental gene networks implement the dynamic regulatory mechanisms that pattern and shape the organism. Over evolutionary time, the wiring of these networks changes, yet the patterning outcome is often preserved, a phenomenon known as "system drift." System drift is illustrated by the gap gene network-involved in segmental patterning-in dipter...

Understanding eukaryotic transcriptional regulation and its role in development and pattern formation is one of the big challenges in biology today. Most attempts at tackling this problem either focus on the molecular details of transcription factor binding, or aim at genome-wide prediction of expression patterns from sequence through bioinformatic...

Studying the dynamics of networks rather than the individual components is essential for our understanding of complex regulatory phenomena. Only by adopting process philosophy as the appropriate conceptual framework can the true potential of systems biology be realized.

Developmental gene networks implement the dynamic regulatory mechanisms that pattern and shape the organism. Over evolutionary time, the wiring of these networks changes, yet the patterning outcome is often preserved, a phenomenon known as “system drift”. System drift is illustrated by the gap gene network—involved in segmental patterning—in dipter...

Gap genes are involved in segment determination during early development in dipteran insects (flies, midges, and mosquitoes). We carried out a systematic quantitative comparative analysis of the gap gene network across different dipteran species. Our work provides mechanistic insights into the evolution of this pattern-forming network. As a central...

Axis specification and segment determination in dipteran insects are an excellent model system for comparative analyses of gene network evolution. Antero-posterior polarity of the embryo is established through systems of maternal morphogen gradients. In Drosophila melanogaster, the anterior system acts through opposing gradients of Bicoid (Bcd) and...

In a recent opinion piece, Denis Duboule has claimed that the increasing shift towards systems biology is driving evolutionary and developmental biology apart, and that a true reunification of these two disciplines within the framework of evolutionary developmental biology (EvoDevo) may easily take another 100 years. He identifies methodological, e...

RNAi dataset. DOI: http://dx.doi.org/10.7554/eLife.04785.021

Boundary positions/shifts and domain widths/overlaps contain tables with numerical comparisons of expression data between M. abdita and D. melanogaster. (A) Comparison of expression data between M. abdita and D. melanogaster: gap domain boundary positions. (B) Comparison of expression data between M. abdita and D. melanogaster: gap domain widths. (...

Megaselia segmentation gene expression. DOI: http://dx.doi.org/10.7554/eLife.04785.020

Maternal co-ordinate and terminal gap gene mRNA expression dataset for M. abdita. This file contains a table with numbers of embryos in our dataset for maternal co-ordinate and terminal gap gene mRNA expression in M. abdita. DOI: http://dx.doi.org/10.7554/eLife.04785.018

We present SuperFly (http://superfly.crg.eu), a relational database for quantified spatio-temporal expression data of segmentation genes during early development in different species of dipteran insects (flies, midges and mosquitoes). SuperFly has a special focus on emerging non-drosophilid model systems. The database currently includes data of hig...

Dynamic modelling is one of the cornerstones of systems biology. Many research efforts are currently being invested in the development and exploitation of large-scale kinetic models. The associated problems of parameter estimation (model calibration) and optimal experimental design are particularly challenging. The community has already developed m...

Understanding the developmental and evolutionary dynamics of regulatory networks is essential if we are to explain the non-random distribution of phenotypes among the diversity of organismic forms. Here, we present a comparative analysis of one of the best understood developmental gene regulatory networks today: the gap gene network involved in ear...

In this paper, we illustrate how dynamical systems theory can provide a unifying conceptual framework for evolution of biological regulatory systems. Our argument is that the genotype–phenotype map can be characterized by the phase portrait of the underlying regulatory process. The features of this portrait – such as attractors with associated basi...

Waddington's epigenetic landscape is an intuitive metaphor for the developmental and evolutionary potential of biological regulatory processes. It emphasises time-dependence and transient behaviour. Nowadays, we can derive this landscape by modelling a specific regulatory network as a dynamical system and calculating its so-called potential surface...

Evolutionary systems biology (ESB) aims to integrate methods from systems biology and evolutionary biology to go beyond the current limitations in both fields. This article clarifies some conceptual difficulties of this integration project, and shows how they can be overcome. The main challenge we consider involves the integration of evolutionary b...

Comparative studies of developmental processes are one of the main approaches to evolutionary developmental biology (evo-devo). Over recent years, there has been a shift of focus from the comparative study of particular regulatory genes to the level of whole gene networks. Reverse-engineering methods can be used to computationally reconstitute and...

Model organisms, such as Drosophila melanogaster, provide powerful experimental tools for the study of development. However, approaches using model systems need to be complemented by comparative studies for us to gain a deeper understanding of the functional properties and evolution of developmental processes. New model organisms need to be establi...

Model organisms, such as Drosophila melanogaster, allow us to address a wide range of biological questions with experimental rigour. However, studies in model species need to be complemented by comparative studies if we are to fully understand the functional properties and evolutionary history of developmental processes. The establishment of new mo...

Author Summary The analysis of pattern-forming gene networks is largely focussed on transcriptional regulation. However, post-transcriptional events, such as translation and regulation of protein stability also play important roles in the establishment of protein expression patterns and levels. In this study, we use a reverse-engineering approach—f...

Amino acid alignment used for phylogenetic analysis

Bayesian phylogenetic analysis of BMP sequences