Spatial Transcriptomics of Nematodes Identifies Sperm Cells as a Source of Genomic Novelty and Rapid Evolution

Abstract Divergence of gene function and expression during development can give rise to phenotypic differences at the level of cells, tissues, organs, and ultimately whole organisms. To gain insights into the evolution of gene expression and novel genes at spatial resolution, we compared the spatially resolved transcriptomes of two distantly related nematodes, Caenorhabditis elegans and Pristionchus pacificus, that diverged 60–90 Ma. The spatial transcriptomes of adult worms show little evidence for strong conservation at the level of single genes. Instead, regional expression is largely driven by recent duplication and emergence of novel genes. Estimation of gene ages across anatomical structures revealed an enrichment of novel genes in sperm-related regions. This provides first evidence in nematodes for the “out of testis” hypothesis that has been previously postulated based on studies in Drosophila and mammals. “Out of testis” genes represent a mix of products of pervasive transcription as well as fast evolving members of ancient gene families. Strikingly, numerous novel genes have known functions during meiosis in Caenorhabditis elegans indicating that even universal processes such as meiosis may be targets of rapid evolution. Our study highlights the importance of novel genes in generating phenotypic diversity and explicitly characterizes gene origination in sperm-related regions. Furthermore, it proposes new functions for previously uncharacterized genes and establishes the spatial transcriptome of Pristionchus pacificus as a catalog for future studies on the evolution of gene expression and function.

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Inter-species comparison of the orientation algorithm directing larval chemotaxis in the genus Drosophila

10.1101/2021.09.17.460740 ◽

2021 ◽

Author(s):

Elie Fink ◽

Matthieu Louis

Keyword(s):

Neural Circuits ◽

Rapid Evolution ◽

Structure And Function ◽

Olfactory Behavior ◽

Species Comparison ◽

Closely Related Species ◽

Genetic Studies ◽

Phenotypic Differences ◽

Peripheral Olfactory System ◽

And Function

Animals differ in their appearances and behaviors. While many genetic studies have addressed the origins of phenotypic differences between fly species, we are still lacking a quantitative assessment of the variability in the way different fly species behave. We tackled this question in one of the most robust behaviors displayed by Drosophila: chemotaxis. At the larval stage, Drosophila melanogaster navigate odor gradients by combining four sensorimotor routines in a multilayered algorithm: a modulation of the overall locomotor speed and turn rate; a bias in turning during down-gradient motion; a bias in turning toward the gradient; the local curl of trajectories toward the gradient ("weathervaning"). Using high-resolution tracking and behavioral quantification, we characterized the olfactory behavior of eight closely related species of the Drosophila group in response to 19 ecologically-relevant odors. Significant changes are observed in the receptive field of each species, which is consistent with the rapid evolution of the peripheral olfactory system. Our results reveal substantial inter-species variability in the algorithms directing larval chemotaxis. While the basic sensorimotor routines are shared, their parametric arrangements can vary dramatically across species. The present analysis sets the stage for deciphering the evolutionary relationships between the structure and function of neural circuits directing orientation behaviors in Drosophila.

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Exploring the Caenorhabditis elegans and Drosophila melanogaster genomes to understand neuropeptide and peptidase function

Biochemical Society Transactions ◽

10.1042/bst0280464 ◽

2000 ◽

Vol 28 (4) ◽

pp. 464-469 ◽

Cited By ~ 12

Author(s):

D. Coates ◽

R. Siviter ◽

R. E. Isaac

Keyword(s):

Drosophila Melanogaster ◽

Caenorhabditis Elegans ◽

Comparative Studies ◽

Gene Families ◽

Human Condition ◽

Form And Function ◽

And Function ◽

The Human Condition

Comparison of peptidase gene families in the newly released Drosophila melanogaster and Caenorhabditis elegans genomes highlights important differences in peptidase distributions with relevance to the evolution of both form and function in these two organisms and can help to identify the most appropriate model when using comparative studies relevant to the human condition.

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Individual differences in frontolimbic circuitry and anxiety emerge with adolescent changes in endocannabinoid signaling across species

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1600013113 ◽

2016 ◽

Vol 113 (16) ◽

pp. 4500-4505 ◽

Cited By ~ 27

Author(s):

Dylan G. Gee ◽

Robert N. Fetcho ◽

Deqiang Jing ◽

Anfei Li ◽

Charles E. Glatt ◽

...

Keyword(s):

Gene Expression ◽

Anxiety Disorders ◽

Neural Circuit ◽

Fatty Acid Amide Hydrolase ◽

Acid Amide ◽

Genetic Alterations ◽

Phenotypic Differences ◽

Brain Circuitry ◽

Amide Hydrolase ◽

And Function

Anxiety disorders peak in incidence during adolescence, a developmental window that is marked by dynamic changes in gene expression, endocannabinoid signaling, and frontolimbic circuitry. We tested whether genetic alterations in endocannabinoid signaling related to a common polymorphism in fatty acid amide hydrolase (FAAH), which alters endocannabinoid anandamide (AEA) levels, would impact the development of frontolimbic circuitry implicated in anxiety disorders. In a pediatric imaging sample of over 1,000 3- to 21-y-olds, we show effects of the FAAH genotype specific to frontolimbic connectivity that emerge by ∼12 y of age and are paralleled by changes in anxiety-related behavior. Using a knock-in mouse model of the FAAH polymorphism that controls for genetic and environmental backgrounds, we confirm phenotypic differences in frontoamygdala circuitry and anxiety-related behavior by postnatal day 45 (P45), when AEA levels begin to decrease, and also, at P75 but not before. These results, which converge across species and level of analysis, highlight the importance of underlying developmental neurobiology in the emergence of genetic effects on brain circuitry and function. Moreover, the results have important implications for the identification of risk for disease and precise targeting of treatments to the biological state of the developing brain as a function of developmental changes in gene expression and neural circuit maturation.

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Molecular topography of an entire nervous system

10.1101/2020.12.15.422897 ◽

2020 ◽

Author(s):

Seth R Taylor ◽

Gabriel Santpere ◽

Alexis Weinreb ◽

Alec Barrett ◽

Molly B. Reilly ◽

...

Keyword(s):

Gene Expression ◽

Nervous System ◽

Web Application ◽

Gene Families ◽

Regulatory Elements ◽

Individual Neuron ◽

Specific Gene ◽

C Elegans ◽

Underlying Mechanisms ◽

And Function

SummaryNervous systems are constructed from a deep repertoire of neuron types but the underlying gene expression programs that specify individual neuron identities are poorly understood. To address this deficit, we have produced an expression profile of all 302 neurons of the C. elegans nervous system that matches the single cell resolution of its anatomy and wiring diagram. Our results suggest that individual neuron classes can be solely identified by combinatorial expression of specific gene families. For example, each neuron class expresses unique codes of ∼23 neuropeptide-encoding genes and ∼36 neuropeptide receptors thus pointing to an expansive “wireless” signaling network. To demonstrate the utility of this uniquely comprehensive gene expression catalog, we used computational approaches to (1) identify cis-regulatory elements for neuron-specific gene expression across the nervous system and (2) reveal adhesion proteins with potential roles in synaptic specificity and process placement. These data are available at cengen.org and can be interrogated at the web application CengenApp. We expect that this neuron-specific directory of gene expression will spur investigations of underlying mechanisms that define anatomy, connectivity and function throughout the C. elegans nervous system.

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Divergent gene expression in the conserved dauer stage of the nematodes Pristionchus pacificus and Caenorhabditis elegans

BMC Genomics ◽

10.1186/1471-2164-13-254 ◽

2012 ◽

Vol 13 (1) ◽

pp. 254 ◽

Cited By ~ 26

Author(s):

Amit Sinha ◽

Ralf J Sommer ◽

Christoph Dieterich

Keyword(s):

Gene Expression ◽

Caenorhabditis Elegans ◽

Pristionchus Pacificus ◽

Divergent Gene

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Adaptive noise

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2013.1104 ◽

2013 ◽

Vol 280 (1767) ◽

pp. 20131104 ◽

Cited By ~ 50

Author(s):

Mark Viney ◽

Sarah E. Reece

Keyword(s):

Gene Expression ◽

Gene Networks ◽

Phenotypic Diversity ◽

Biological Systems ◽

Bet Hedging ◽

Hedging Strategy ◽

Phenotypic Differences ◽

Fitness Benefits ◽

Adaptive Noise ◽

Noise In Gene Expression

In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise and that noise may be adaptive. For example, gene networks can generate bistable states resulting in phenotypic diversity and switching among individual cells of a genotype, which may be a bet hedging strategy. Here, we review the sources of noise in gene expression, the extent to which noise in biological systems may be adaptive and suggest that applying evolutionary rigour to the study of noise is necessary to fully understand organismal phenotypes.

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Splotch: Robust estimation of aligned spatial temporal gene expression data

10.1101/757096 ◽

2019 ◽

Cited By ~ 2

Author(s):

Tarmo Äijö ◽

Silas Maniatis ◽

Sanja Vickovic ◽

Kristy Kang ◽

Miguel Cuevas ◽

...

Keyword(s):

Gene Expression ◽

Expression Data ◽

Rna Seq ◽

Computational Framework ◽

Temporal Gene Expression ◽

Tissue Sections ◽

Spatially Resolved ◽

Transcriptomics Data ◽

Approaches To Study ◽

And Function

AbstractSpatial genomics technologies enable new approaches to study how cells interact and function in intact multicellular environments but present a host of technical and computational challenges. Here we describe Splotch, a novel computational framework for the analysis of spatially resolved transcriptomics data. Splotch aligns transcriptomics data from multiple tissue sections and timepoints to generate improved posterior estimates of gene expression. We demonstrate alignment of a large corpus of single-cell RNA-seq data into an automatically generated spatial-temporal coordinate and study optimal design for spatial transcriptomics experiments.

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Epigenetic Profiling Identifies Novel Genes for Ascending Aortic Aneurysm Formation with Bicuspid Aortic Valves

The Heart Surgery Forum ◽

10.1532/hsf.1247 ◽

2015 ◽

Vol 18 (4) ◽

pp. 134 ◽

Cited By ~ 12

Author(s):

Asad A Shah

Keyword(s):

Gene Expression ◽

Aortic Aneurysm ◽

Methylation Status ◽

Aortic Aneurysms ◽

Aortic Valves ◽

Ascending Aortic Aneurysm ◽

Novel Genes ◽

Aneurysm Formation ◽

Aortic Replacement ◽

Bicuspid Aortic Valves

Background: Bicuspid aortic valves predispose to ascending aortic aneurysms, but the mechanisms underlying this aortopathy remain incompletely characterized. We sought to identify epigenetic pathways predisposing to aneurysm formation in bicuspid patients.Methods: Ascending aortic aneurysm tissue samples were collected at the time of aortic replacement in subjects with bicuspid and trileaflet aortic valves. Genome-wide DNA methylation status was determined on DNA from tissue using the Illumina 450K methylation chip, and gene expression was profiled on the same samples using Illumina Whole-Genome DASL arrays. Gene methylation and expression were compared between bicuspid and trileaflet individuals using an unadjusted Wilcoxon rank sum test. Results: Twenty-seven probes in 9 genes showed significant differential methylation and expression (P<5.5x10-4). The top gene was protein tyrosine phosphatase, non-receptor type 22 (PTPN22), which was hypermethylated (delta beta range: +15.4 to +16.0%) and underexpressed (log 2 gene expression intensity: bicuspid 5.1 vs. trileaflet 7.9, P=2x10-5) in bicuspid patients, as compared to tricuspid patients. Numerous genes involved in cardiovascular development were also differentially methylated, but not differentially expressed, including ACTA2 (4 probes, delta beta range: -10.0 to -22.9%), which when mutated causes the syndrome of familial thoracic aortic aneurysms and dissectionsConclusions: Using an integrated, unbiased genomic approach, we have identified novel genes associated with ascending aortic aneurysms in patients with bicuspid aortic valves, modulated through epigenetic mechanisms. The top gene was PTPN22, which is involved in T-cell receptor signaling and associated with various immune disorders. These differences highlight novel potential mechanisms of aneurysm development in the bicuspid population.

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