Mapping epigenetic divergence in the massive radiation of Lake Malawi cichlid fishes.

Epigenetic variation modulates gene expression and can be heritable. However, knowledge of the contribution of epigenetic divergence to adaptive diversification in nature remains limited. The massive evolutionary radiation of Lake Malawi cichlid fishes displaying extensive phenotypic diversity despite extremely low sequence divergence is an excellent system to study the epigenomic contribution to adaptation. Here, we present a comparative genome-wide methylome and transcriptome study, focussing on liver and muscle tissues in phenotypically divergent cichlid species. In both tissues we find substantial methylome divergence among species. Differentially methylated regions (DMR), enriched in evolutionary young transposons, are associated with transcription changes of ecologically-relevant genes related to energy expenditure and lipid metabolism, pointing to a link between dietary ecology and methylome divergence. Unexpectedly, half of all species-specific DMRs are shared across tissues and are enriched in developmental genes, likely reflecting distinct epigenetic developmental programmes. Our study reveals substantial methylome divergence in closely-related cichlid fishes and represents a resource to study the role of epigenetics in species diversification

Lateral line system diversification during the early stages of ecological speciation in cichlid fish

Background: The mechanosensory lateral line system is an important sensory modality in fishes, informing multiple behaviours related to survival including finding food and navigating in dark environments. Given its ecological importance, we may expect lateral line morphology to be under disruptive selection early in the ecological speciation process. Here we quantify the lateral line system morphology of two ecomorphs of the cichlid fish Astatotilapia calliptera in crater Lake Masoko that have diverged from common ancestry within the past 1,000 years. Results: Based on geometric morphometric analyses of CT scans, we show that the zooplanktivorous benthic ecomorph that dominates the deeper waters of the lake has large cranial lateral line canal pores, relative to those of the nearshore invertebrate-feeding littoral ecomorph found in the shallower waters. In contrast, fluorescence imaging revealed no evidence for divergence between ecomorphs in the number of either superficial or canal neuromasts. We illustrate the magnitude of the variation we observe in Lake Masoko A. calliptera in the context of the neighbouring Lake Malawi mega-radiation that comprises over 700 species. Conclusions: These results provide the first evidence of divergence in this often-overlooked sensory modality in the early stages of ecological speciation, suggesting that it may have a role in the broader adaptive radiation process

Author Correction: Evolutionary divergence of novel open reading frames in cichlids speciation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.</jats:p

Evolutionary divergence of novel open reading frames in cichlids speciation

Funder: DBT-Cambridge LectureshipFunder: Wellcome Trust Senior Investigator AwardAbstract: Novel open reading frames (nORFs) with coding potential may arise from noncoding DNA. Not much is known about their emergence, functional role, fixation in a population or contribution to adaptive radiation. Cichlids fishes exhibit extensive phenotypic diversification and speciation. Encounters with new environments alone are not sufficient to explain this striking diversity of cichlid radiation because other taxa coexistent with the Cichlidae demonstrate lower species richness. Wagner et al. analyzed cichlid diversification in 46 African lakes and reported that both extrinsic environmental factors and intrinsic lineage-specific traits related to sexual selection have strongly influenced the cichlid radiation, which indicates the existence of unknown molecular mechanisms responsible for rapid phenotypic diversification, such as emergence of novel open reading frames (nORFs). In this study, we integrated transcriptomic and proteomic signatures from two tissues of two cichlids species, identified nORFs and performed evolutionary analysis on these nORF regions. Our results suggest that the time scale of speciation of the two species and evolutionary divergence of these nORF genomic regions are similar and indicate a potential role for these nORFs in speciation of the cichlid fishes

Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.

Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.RCUK Cancer Research UK ERC H2020 Wellcome Trus

Epigenetic variability and inheritance in East African cichlid fishes

The hundreds of cichlid species forming part of the radiation of East African Lakes show a remarkable diversity of phenotypic and ecological adaptation. Despite this, recent studies highlighted that genetic diversity within the radiation is among the lowest ever observed in vertebrates. Such a high phenotype/genotype diversity ratio makes cichlids a promising system to investigate the role of genetics and, for the first time at a species level, epigenetics in the context of adaptation and convergent evolution. Yet, the molecular mechanisms and, in particular, any epigenetic aspects underlying such phenotypic diversity and speciation success remain largely unknown. Here, I focus on whole-genome DNA methylation (methylome), a heritable and dynamic epigenetic mark that has been reported to be responsible for rapid and transmissible changes in phenotype in plants and mammals. In light with phenotypic plasticity related to diet adaptation, I hypothesise that the liver methylome may affect liver function and thus be related to diet. I thus performed sequencing of liver tissues of different cichlid species presenting distinct eco-morphological and trophic adaptation from both Lake Malawi and crater lake Massoko, Tanzania. The main results reveal striking differences in methylome at conserved underlying DNA sequences – some variation shared in cichlids of both lakes. Furthermore, I observe an enrichment for methylome variation in transposable elements (TE) and promoter regions. Remarkably, most of the variation (ca 80%) common to fishes from both lakes are located in TEs and is, in part, correlated with differential expression levels at some key metabolic and developmental genes in liver. This suggests a possible conserved role of TE-related methylome in the adaptation of liver function. Furthermore, I generated inter-species hybrids to investigate the inheritance of DNAme variation in cichlids. The liver methylome of F1 hybrids, although mostly resembling parental methylomes, exhibited some level of divergence, suggesting unique DNAme patterns in hybrid offspring and possible transgressive segregation. I conclude there might be a conserved crosstalk between the local environment and methylome in different natural populations of cichlids. The results presented in this thesis postulate an important role of natural DNA methylation variation in promoting adaptive phenotypic diversification in divergent habitats during the early stages of speciation.Wellcome Genetics Society Wolfson College, Cambridge Universit

Early life stress in fathers improves behavioural flexibility in their offspring

Traumatic experiences in childhood can alter behavioural responses and increase the risk for psychopathologies across life, not only in the exposed individuals but also in their progeny. In some conditions, such experiences can however be beneficial and facilitate the appraisal of adverse environments later in life. Here we expose newborn mice to unpredictable maternal separation combined with unpredictable maternal stress (MSUS) for 2 weeks and assess the impact on behaviour in the offspring when adult. We show that MSUS in male mice favours goal-directed behaviours and behavioural flexibility in the adult offspring. This effect is accompanied by epigenetic changes involving histone post-translational modifications at the ​mineralocorticoid receptor (​MR) gene and decreased ​MR expression in the hippocampus. Mimicking these changes pharmacologically in vivo reproduces the behavioural phenotype. These findings highlight the beneficial impact that early adverse experiences can have in adulthood, and the implication of epigenetic modes of gene regulation

Lateral line system diversification during the early stages of ecological speciation in cichlid fish.

Acknowledgements: We thank Mary Kishe and Asilatu Shechonge at TAFIRI Dar es Salaam for their assistance with fieldwork planning and logistics, Joseph Masore at TAFIRI Kyela for help in the field, Zacharia J. Mwampwani for logistical support, and Thomas Masero and Charles Malela for assistance with capturing fish. We thank Richard Durbin, Hannah Munby, Bettina Fischer, Eric Miska and Tyler Linderoth for fieldwork support and whole-genome sequence data associated with genetic assignment of fish. We thank Alan Hudson for the spectrophotometry data. We are grateful to Elizabeth G. Martin-Silverstone and Thomas Davies for their expertise and guidance with CT scanning and associated software. We thank Julie Johnson for cichlid fish illustrations. Thanks to Julia Day and Stephen Montgomery for useful discussions. Duncan Edgley was supported by a NERC GW4+ Doctoral Training Partnership studentship from the Natural Environment Research Council [NE/L002434/1]. Sampling permission was issued by the Tanzania Commission for Science and Technology, permit number 2019-549-NA-2019-357.BACKGROUND: The mechanosensory lateral line system is an important sensory modality in fishes, informing multiple behaviours related to survival including finding food and navigating in dark environments. Given its ecological importance, we may expect lateral line morphology to be under disruptive selection early in the ecological speciation process. Here we quantify the lateral line system morphology of two ecomorphs of the cichlid fish Astatotilapia calliptera in crater Lake Masoko that have diverged from common ancestry within the past 1,000 years. RESULTS: Based on geometric morphometric analyses of CT scans, we show that the zooplanktivorous benthic ecomorph that dominates the deeper waters of the lake has large cranial lateral line canal pores, relative to those of the nearshore invertebrate-feeding littoral ecomorph found in the shallower waters. In contrast, fluorescence imaging revealed no evidence for divergence between ecomorphs in the number of either superficial or canal neuromasts. We illustrate the magnitude of the variation we observe in Lake Masoko A. calliptera in the context of the neighbouring Lake Malawi mega-radiation that comprises over 700 species. CONCLUSIONS: These results provide the first evidence of divergence in this often-overlooked sensory modality in the early stages of ecological speciation, suggesting that it may have a role in the broader adaptive radiation process