During the last decade, understanding the causes of phenotypic diversification has become one of the most puzzling topics of today’s biology (Romero et al., 2012). A major motivation of current evolutionary biology is to identify the genetic basis of interspecific phenotypic variation. This obviously includes the study of the pronounced phenotypic shifts that have accumulated in humans since our lineage diverged from the common ancestor with chimpanzees (Khaitovich et al., 2006) five to seven million years ago (Glazko and Nei, 2003). Over the past century, evolutionary geneticists have thus focused on identifying the genetic basis of this famous phenotypic diversification event. Surprisingly, it appeared that the genetic distance between humans and chimpanzees is possibly too small to account for their substantial organismal differences (King and Wilson, 1975) and it has therefore been suggested that evolutionary changes in anatomy and behaviour might have been triggered through regulatory evolution rather than through variations in coding sequences (King and Wilson, 1975). Large-scale studies of gene expression evolution over longer evolutionary distances are now possible as a result of the increasing number of available sequenced transcriptomes. Extensive comparative surveys demonstrate that variation in gene expression patterns play a key role in the evolution of morphological differences (Brawand et al., 2011; Necsulea and Kaessmann, 2014; Romero et al., 2012). Nevertheless, the evolutionary dynamics of gene expression has so far mainly been studied between species that diverged long ago, whereas comparatively little is known about how gene expression evolves during rapid organismal diversification. Adaptive radiation, which is defined as the rapid proliferation of eco-morphological diversity within an organismal lineage on the basis of accelerated adaptation to distinct ecological niches (Gavrilets and Losos, 2009; Schluter, 2000), can be responsible for extremely rapid morphological diversification (Berner and Salzburger, 2015). One of the most striking examples of adaptive radiation is found in East African Lake Tanganyika, where hundreds of cichlid fish species have evolved within a few million years only (Berner and Salzburger, 2015; Salzburger, 2018; Salzburger and Meyer, 2004). Cichlids occupy a great variety of ecological niches (Berner and Salzburger, 2015; Ronco et al., 2019; Salzburger, 2018) and are drastically diverse in many phenotypic traits (Berner and Salzburger, 2015; Salzburger, 2018). The cichlids’ impressive ability to rapidly diversify and adapt to new environments has been documented multiple times and in different geographic regions (Crispo and Chapman, 2010; Härer et al., 2017; Muschick et al., 2011) and extensive efforts have been made to identify and explain the genetic basis underlying and allowing such remarkable events (Brawand et al., 2014). Several molecular mechanisms (e.g. excess of gene duplication, expression divergence associated with transposable element insertions, accelerated coding sequence evolution) have been associated with rapid diversification in cichlids (Brawand et al., 2014). A particularly promising candidate factor is gene expression regulation (Brawand et al., 2014). It has been shown at several occasions that gene expression variations account for important phenotypic shifts observed among cichlids (Colombo et al., 2013; Henning et al., 2013; Hofmann et al., 2009; Santos et al., 2016, 2014), including the differential expression of opsin genes for adaptation of the senses to different light environments (Carleton and Kocher, 2001; Hofmann et al., 2009; Seehausen et al., 2008). And yet, it is not fully understood how intrinsic factors and external events interplay to promote this exceptional phenotypic diversity (Losos, 2010; Salzburger, 2018, 2009; Seehausen, 2007; Yoder et al., 2010). The main goal of this thesis is to retrace the evolutionary history of the Tanganyikan cichlids from different perspectives (genomic, transcriptomic and ecology) and extend the current knowledge of how selection acts on an entire biological system. It is an integrative approach in which I combined bioinformatic and experimental methods to understand the inception of such an impressive evolutionary process at the level of the transcriptome. This thesis is developed along two axes. The first part of the thesis (Chapter 1-6) is dedicated to an in-depth exploration of the entire Lake Tanganyikan cichlid radiation (~250 species). By focusing on the species flock as a whole, this survey provides a unique opportunity to gain insights into the causes and triggers, the progression and the resultant communities of an adaptive radiation. The first chapter entitled “The evolution of gene expression levels during rapid organismal diversification” focuses on understanding to what extend gene expression evolution has contributed to the rapid evolution of the astonishing diversity of cichlids in Lake Tanganyika. For a comprehensive analysis, we sequenced the transcriptomes of six organs from 73 emblematic cichlid species representing all the different Tanganyikan cichlid lineages (Ronco et al., 2019). We selected six organs involved in ecological (lowerpharyngeal jaw (LPJ), liver, gills) and behavioural (brain, testis, ovary) important traits known to be very diverse in cichlids (Fig.1) (Baldo et al., 2011; Böhne et al., 2013; Schneider et al., 2014). By comparing gene expression patterns across the species tree, we investigated the rate of gene expression evolution among organs, lineage and transcriptome parts (coding vs. non-coding) and studied the difference in the degree of expression specificity among organs and lineages. The second chapter entitled “Tempo and mode of sex chromosome turnovers in an adaptive radiation” focuses on another component of speciation, namely the evolution of sex chromosome systems. In several large animal clades, sex chromosomes are conserved and shared across many species, whereas other clades undergo frequent sex chromosome turnovers leading to an uneven distribution of sex chromosome diversity (Bachtrog et al., 2014). In particular, many fish families feature young sex chromosomes and experience rapid turnovers (Kitano and Peichel, 2012). East African cichlids recently emerged as a model to study the evolutionary dynamics of sex determination (Gammerdinger et al., 2018). As we collected male and female specimens for each species of cichlids (Chapter 1 and chapter 4), we use expression (Chapter 1) and genomic (Chapter 4) data to investigate sex chromosome evolution in the Tanganyikan cichlids. We aimed at identifying new sex chromosome systems and at providing a better understanding of when and how new sex chromosomes evolve in a short evolutionary framework by focusing on a case of explosive speciation accompanied by spectacular phenotypic diversity. In the third chapter which is entitled “The transcriptional basis of adaptive diversification in the lower pharyngeal jaw bone of cichlid fishes”, we focused on the association between gene expression and the morphology of an important trophic trait of cichlid fishes, the lower pharyngeal jaw (LPJ) (Gunter and Meyer, 2014; Muschick et al., 2012, 2011; Schneider et al., 2014). To gain new insights on how gene expression modulates LPJ morphology at a higher taxonomic level, we correlated gene expression levels (see Chapter 1 for more details) of 71 cichlid species – covering the entire spectrum of the eco-morphological and genetic diversity of the Lake Tanganyika cichlid adaptive radiation – with their LPJ morphology (see Chapter 4 for more details). With this approach, we aimed at identifying genes and functional categories involved in the LPJ morphological divergence observed across the Lake Tanganyika cichlid adaptive radiation but also at measuring how much gene expression levels support those important morphological divergence. Chapter 4 is entitled “Drivers, dynamics and progression of a massive adaptive radiation in African cichlid fish” and focuses on the in-depth investigation of nearly the entire taxonomic diversity of the Tanganyika cichlid adaptive radiation. Based on whole genome sequencing, multivariate morphological measurements of several important trophic traits (e.g. body shape and LPJ) and ecological indicators (e.g. stable isotopes), this chapter focused on bringing new insights on how genetic change is associated with phenotypic and ecological diversity and trace back patterns of eco-morphological evolution through the phylogenetic history of the radiation. Chapter 5 is entitled “Community assembly patterns and niche evolution in the species-flock of cichlid fishes from East African Lake Tanganyika” and focuses on characterizing the community structure and the niche evolution of the adaptive radiation of Lake Tanganyika cichlids. To study underwater communities, point-combination transect (PCT) (Widmer et al., 2019) was used allowing the investigation of habitat differentiation and co-occurrence across almost the entire radiation. Chapter 6 “Does eDNA within sediments reflect local cichlid assemblages in Lake Tanganyika?” explores the applicability of environmental DNA (eDNA) being used to asses the cichlid fish diversity at various sites at Lake Tanganyika (Klymus et al., 2017; Lobo et al., 2017; Thomsen and Willerslev, 2015). Compared with PCT data (Chapter 5), chapter 6 compiled an ideal data set for proof of concept of PCT and discusses the validity of eDNA as a tool for future community assessments in cichlids. The second part of this thesis focuses on a very central concept of adaptive radiation: adaptation to new ecological niches (Gavrilets and Losos, 2009; Schluter, 2000). When encountering ecological opportunities, species during an adaptive radiation rapidly adapt and diversify to fill available niches (Gavrilets and Losos, 2009; Schluter, 2000). This part of the thesis investigates the transcriptomic basis of adaptation to different environments in one particular cichlid species, the East African haplochromine Astatotilapia burtoni (Chapter 7-8). This fish has adapted to lake and river environments and different pairs of lake-stream populations, representing different stages of the “speciation continuum”, can be found around Lake Tanganyika (Pauquet et al., 2018; Theis et al., 2014). Over the past decades, A. burtoni has been established as a cichlid model system to study many key questions in ecology and evolutionary biology (behaviour (Theis et al., 2012), neuronal processes (Huffman et al., 2015), sex determination (Böhne et al., 2016; Göppert et al., 2016; Heule et al., 2014; Roberts et al., 2016), pigmentation (Santos et al., 2014), genomics and speciation (Brawand et al., 2014; Pauquet et al., 2018; Salzburger, 2018). As a consequence, A. burtoni is also an emerging system in developmental biology (Heule and Salzburger, 2011; Woltering et al., 2018), which is greatly facilitated by the availability of a reference genome (Brawand et al., 2014). This genome, however, remains fragmented (scaffold level assembly) and with poorer annotations as compared to the most widely used cichlid reference genome, the one of the Nile tilapia Oreochromis niloticus, which has been assembled to the chromosome level (Brawand et al., 2014; Conte et al., 2017). Chapter 7 “Time matters! Developmental shift in gene expression between the head and the trunk region of the cichlid fish Astatotilapia burtoni” investigates gene expression throughout development in A. burtoni. Combining RNA-sequencing from different developmental time points as well as integrating adult gene expression data, we aimed at creating new genome annotations for this established cichlid model system. Using the newly constructed comprehensive reference transcriptome, we investigated differential gene expression and gene expression dynamics through time and across different body parts. In the last chapter of the thesis, which is entitled “From river to lake: Gene expression remodelling and immune response during adaptation to new environments” we focus on adaptive phenotypic plasticity to different environments in A. burtoni. We aimed at characterizing this plasticity by describing gene expression and microbiota communities of lake and stream ecotypes in the wild, and describing how they change when exposed to environmental changes. The seven chapters of this thesis are followed by an overall discussion, which quotes all chapters’ results and brings into perspective how such an integrative project allows addressing key questions in evolutionary biology. I would like to note that all the chapters presented in this thesis are the results of valuable collaborations. My personal contribution to each chapter is described in the “Author Contributions” section of each chapter.