Epigenetic Priming by Hypomethylation Enhances the Immunogenic Potential of Tolinapant in T-cell Lymphoma.

Programmed cell death mechanisms are important for the regulation of tumor development and progression. Evasion of and resistance to apoptosis are significant factors in tumorigenesis and drug resistance. Bypassing apoptotic pathways and eliciting another form of regulated cell death, namely necroptosis, an immunogenic cell death (ICD), may override apoptotic resistance. Here, we present the mechanistic rationale for combining tolinapant, an antagonist of the inhibitor of apoptosis proteins (IAP), with decitabine, a hypomethylating agent (HMA), in T-cell lymphoma (TCL). Tolinapant treatment alone of TCL cells in vitro and in syngeneic in vivo models demonstrated that ICD markers can be upregulated, and we have shown that epigenetic priming with decitabine further enhances this effect. The clinical relevance of ICD markers was confirmed by the direct measurement of plasma proteins from patients with peripheral TCL treated with tolinapant. We showed increased levels of necroptosis in TCL lines, along with the expression of cancer-specific antigens (such as cancer testis antigens) and increases in genes involved in IFN signaling induced by HMA treatment, together deliver a strong adaptive immune response to the tumor. These results highlight the potential of a decitabine and tolinapant combination for TCL and could lead to clinical evaluation. SIGNIFICANCE: The IAP antagonist tolinapant can induce necroptosis, a key immune-activating event, in TCL. Combination with DNA hypomethylation enhances tolinapant sensitivity and primes resistant cells by re-expressing necrosome proteins. In addition, this combination leads to increases in genes involved in IFN signaling and neoantigen expression, providing further molecular rationale for this novel therapeutic option.

Molecular phylogeny of the threadfin fishes (Polynemidae) using ultraconserved elements.

Threadfins (Teleostei: Polynemidae) are a group of fishes named for their elongated and threadlike pectoral-fin rays. These fishes are commonly found in the world's tropical and subtropical waters, and are an economically important group for people living in these regions, with more than 100,000 t harvested in recent years. However, we do not have a detailed understanding of polynemid evolutionary history such that these fishes can be monitored, managed and conserved as an important tropical food source. Recent studies hypothesize at least one genus of threadfins is polyphyletic, and no studies have focused on generating a hypothesis of relationship for the Polynemidae using DNA sequences. In this study, we analyse a genomic dataset of ultraconserved-element and mitochondrial loci to construct a phylogeny of the Polynemidae. We recover the threadfins as a clade sister to flatfishes, with the most taxonomically rich genus, Polydactylus, being resolved as polyphyletic. When comparing our dataset to data from previous studies, we find that a few recent broad-scale phylogenies of fishes have incorporated mislabelled, misidentified or chimeric terminals into their analyses, impacting the relationships of threadfins they recover. We highlight these problematic sequences, providing revised identifications based on the data sequenced in this study. We then discuss the intrarelationships of threadfins, highlighting morphological or ecological characters that support the clades we recover.

Antagonism of inhibitors of apoptosis proteins reveals a novel, immune response-based therapeutic approach for T-cell lymphoma.

Tolinapant (ASTX660) is a potent, nonpeptidomimetic antagonist of cellular inhibitor of apoptosis proteins 1 and 2 (cIAP1/2) and X-linked IAP, which is currently being evaluated in a phase 2 study in T-cell lymphoma (TCL) patients. Tolinapant has demonstrated evidence of single-agent clinical activity in relapsed/refractory peripheral TCL and cutaneous TCL. To investigate the mechanism of action underlying the single-agent activity observed in the clinic, we have used a comprehensive translational approach integrating in vitro and in vivo models of TCL confirmed by data from human tumor biopsies. Here, we show that tolinapant acts as an efficacious immunomodulatory molecule capable of inducing complete tumor regression in a syngeneic model of TCL exclusively in the presence of an intact immune system. These findings were confirmed in samples from our ongoing clinical study showing that tolinapant treatment can induce changes in gene expression and cytokine profile consistent with immune modulation. Mechanistically, we show that tolinapant can activate both the adaptive and the innate arms of the immune system through the induction of immunogenic forms of cell death. In summary, we describe a novel role for IAP antagonists as immunomodulatory molecules capable of promoting a robust antitumor immune response in TCL.

Anatomy and evolution of bioluminescent organs in the slimeheads (Teleostei: Trachichthyidae).

Bacterial bioluminescent organs in fishes have a diverse range of tissues of origin, patterns of compartmentalization, and associated light-conducting structures. The morphology of the perianal, bacterial bioluminescent organ of Aulotrachichthys prosthemius was described previously, but the light organ in other species of slimeheads, family Trachichthyidae, is poorly known. Here, we describe the anatomy of the bioluminescent organs in trachichthyids and places the evolution of this light-producing system in the context of a new phylogeny of the Trachichthyoidei to test the hypothesis that bioluminescence evolved twice in the suborder and that the light-producing component derives from the perianal ectoderm. We use gross and histological examination to provide the first description of the bioluminescent organ of Paratrachichthys and four additional species of Aulotrachichthys. Observations also strongly suggest the presence of a perianal bioluminescent organ in Sorosichthys ananasa. The updated phylogeny of the Trachichthyoidei is the first to combine morphological and DNA-sequence (11-gene fragments) evidence, and supports a monophyletic Trachichthyidae with component subfamilies Hoplostethinae and Trachichthyinae, supporting continued recognition of the family Anoplogastridae. All bioluminescent trachichthyoids share a similar bioluminescent-organ structure with elongate chambers filled with bacteria and connected to collecting ducts that, in turn, connect to superficial ducts that lead to and have lining epithelia continuous with the epidermis. In the context of the phylogeny, the bioluminescent organ of trachichthyids is inferred to have evolved as an elaboration of the proctodeum in the ancestor of Aulotrachichthys, Paratrachichthys, and Sorosichthys independently from the structurally similar cephalic bioluminescent organs in Anomalopidae and Monocentridae.

The evolution of specialized dentition in the deep-sea lanternfishes (Myctophiformes).

The evolution of heterodonty, the possession of varied tooth morphologies on the jaws of animals, has been relatively unexplored in ray-finned fishes compared to terrestrial vertebrates, and to an even lesser degree in deep-sea fish lineages. Lanternfishes (Myctophiformes) are an abundant and species-rich group endemic to deep-sea pelagic habitats. In this study, we document the presence of heterodonty on the oral jaws of lanternfishes, identifying differing anatomical and positional variations of dentition. We survey the anatomical variation in tooth morphology on the oral jaws of 114 lanternfish species across 37 genera and integrate our findings with a hypothesis of evolutionary relationships of lanternfishes to infer the number of times heterodonty evolved in this lineage. Our results indicate that heterodonty evolved at least six separate times on the oral jaws of lanternfishes, occurring as variable tooth morphologies in combination with villiform teeth. These combinations of tooth types include villiform plus hooked teeth, villiform plus hooked and recurved teeth, villiform plus spade, tricuspid, and hooked teeth, and villiform plus caniniform teeth. The reoccurring evolution of hooked teeth on the premaxilla and dentary in lanternfishes suggests heterodonty may serve an important functional role in their pelagic deep-sea environment. Hooked teeth could aid in securing and retaining prey in the oral cavity and allow for species to specialize on differing food resources, vital attributes for organisms living in open-ocean habitats.

Salamanders and other amphibians are aglow with biofluorescence.

Biofluorescence is the absorption of electromagnetic radiation (light) at one wavelength followed by its reemission at a lower energy and longer wavelength by a living organism. Previous studies have documented the widespread presence of biofluorescence in some animals, including cnidarians, arthropods, and cartilaginous and ray-finned fishes. Many studies on biofluorescence have focused on marine animals (cnidarians, cartilaginous and ray-finned fishes) but we know comparatively little about the presence of biofluorescence in tetrapods. We show for the first time that biofluorescence is widespread across Amphibia, with a focus on salamanders (Caudata), which are a diverse group with a primarily Holarctic distribution. We find that biofluorescence is not restricted to any particular family of salamanders, there is striking variation in their fluorescent patterning, and the primary wavelengths emitted in response to blue excitation light are within the spectrum of green light. Widespread biofluorescence across the amphibian radiation is a previously undocumented phenomenon that could have significant ramifications for the ecology and evolution of these diverse and declining vertebrates. Our results provide a roadmap for future studies on the characterization of molecular mechanisms of biofluorescence in amphibians, as well as directions for investigations into the potential impact of biofluorescence on the visual ecology and behavior of biofluorescent amphibians.

The first evidence of intrinsic epidermal bioluminescence within ray-finned fishes in the linebelly swallower Pseudoscopelus sagamianus (Chiasmodontidae).

External and histological examination of the photophores of the linebelly swallower Pseudoscopelus sagamianus reveal three epidermal layers of cells that form the light-producing and light-transmitting components of the photophores. Photophores among the examined photophore tracts are not significantly different in structure but the presence of mucous cells in the superficial layers of the photophore suggest continued function of the epidermal photophore in contributing to the mucous coat. This is the first evidence of intrinsic bioluminescence in primarily epidermal photophores reported in ray-finned fishes.

Morphology and evolution of bioluminescent organs in the glowbellies (Percomorpha: Acropomatidae) with comments on the taxonomy and phylogeny of Acropomatiformes.

Bioluminescent organs have evolved many times within teleost fishes and exhibit a wide range of complexity and anatomical derivation. Although some bioluminescent organs have been studied in detail, the morphology of the bacterial light organs in glowbellies (Acropoma) is largely unknown. This study describes the anatomy of the bioluminescent organs in Haneda's Glowbelly (Acropoma hanedai) and the Glowbelly (Acropoma japonicum) and places the evolution of this light-producing system in the context of a new phylogeny of glowbellies and their relatives. Gross and histological examination of the bioluminescent organs indicate that they are derived from perianal ectodermal tissue, likely originating from the developmental proctodeum, contrary to at least one prior suggestion that the bioluminescent organ in Acropoma is of endodermal intestinal derivation. Additionally, anterior bioluminescent organ development in both species is associated with lateral spreading of the bacteria-containing arms of the bioluminescent organ from an initial median structure. In the context of a 16-gene molecular phylogeny, the bioluminescent organ in Acropoma is shown to have evolved within the Acropomatidae in the ancestor of Acropoma. Further, ancestral-states reconstruction demonstrates that the bioluminescent organs in Acropoma evolved independently from the light organs in related howellid and epigonid taxa which have esophageal or intestinally derived bioluminescent organs. Across the acropomatiforms, our reconstructions indicate that bioluminescent organs evolved independently four or five times. Based on the inferred phylogeny of the order where Acropoma and Doederleinia were separated from other traditional acropomatids, the familial taxonomy of the Acropomatidae was modified such that the previously described Malakichthyidae and Synagropidae were recognized. We also morphologically diagnose and describe the family Lateolabracidae.

Light in the darkness: New perspective on lanternfish relationships and classification using genomic and morphological data.

Massive parallel sequencing allows scientists to gather DNA sequences composed of millions of base pairs that can be combined into large datasets and analyzed to infer organismal relationships at a genome-wide scale in non-model organisms. Although the use of these large datasets is becoming more widespread, little to no work has been done in estimating phylogenetic relationships using UCEs in deep-sea fishes. Among deep-sea animals, the 257 species of lanternfishes (Myctophiformes) are among the most important open-ocean lineages, representing half of all mesopelagic vertebrate biomass. With this relative abundance, they are key members of the midwater food web where they feed on smaller invertebrates and fishes in addition to being a primary prey item for other open-ocean animals. Understanding the evolution and relationships of midwater organisms generally, and this dominant group of fishes in particular, is necessary for understanding and preserving the underexplored deep-sea ecosystem. Despite substantial congruence in the evolutionary relationships among deep-sea lanternfishes at higher classification levels in previous studies, the relationships among tribes, genera, and species within Myctophidae often conflict across phylogenetic studies or lack resolution and support. Herein we provide the first genome-scale phylogenetic analysis of lanternfishes, and we integrate these data from across the nuclear genome with additional protein-coding gene sequences and morphological data to further test evolutionary relationships among lanternfishes. Our phylogenetic hypotheses of relationships among lanternfishes are entirely congruent across a diversity of analyses that vary in methods, taxonomic sampling, and data analyzed. Within the Myctophiformes, the Neoscopelidae is inferred to be monophyletic and sister to a monophyletic Myctophidae. The current classification of lanternfishes is incongruent with our phylogenetic tree, so we recommend revisions that retain much of the traditional tribal structure and recognize five subfamilies instead of the traditional two subfamilies. The revised monophyletic taxonomy of myctophids includes the elevation of three former lampanyctine tribes to subfamilies. A restricted Lampanyctinae was recovered sister to Notolychninae. These two clades together were recovered as the sister group to the Gymnoscopelinae. Combined, these three subfamilies were recovered as the sister group to a clade composed of a monophyletic Diaphinae sister to the traditional Myctophinae. Our results corroborate recent multilocus molecular studies that infer a polyphyletic Myctophum in Myctophinae, and a para- or polyphyletic Lampanyctus and Nannobrachium within Lampanyctinae. We resurrect Dasyscopelus and Ctenoscopelus for the independent clades traditionally classified as species of Myctophum, and we place Nannobrachium into the synonymy of Lampanyctus.

A high-resolution mRNA expression time course of embryonic development in zebrafish.

We have produced an mRNA expression time course of zebrafish development across 18 time points from 1 cell to 5 days post-fertilisation sampling individual and pools of embryos. Using poly(A) pulldown stranded RNA-seq and a 3' end transcript counting method we characterise temporal expression profiles of 23,642 genes. We identify temporal and functional transcript co-variance that associates 5024 unnamed genes with distinct developmental time points. Specifically, a class of over 100 previously uncharacterised zinc finger domain containing genes, located on the long arm of chromosome 4, is expressed in a sharp peak during zygotic genome activation. In addition, the data reveal new genes and transcripts, differential use of exons and previously unidentified 3' ends across development, new primary microRNAs and temporal divergence of gene paralogues generated in the teleost genome duplication. To make this dataset a useful baseline reference, the data can be browsed and downloaded at Expression Atlas and Ensembl.

Mirnovo: genome-free prediction of microRNAs from small RNA sequencing data and single-cells using decision forests.

The discovery of microRNAs (miRNAs) remains an important problem, particularly given the growth of high-throughput sequencing, cell sorting and single cell biology. While a large number of miRNAs have already been annotated, there may well be large numbers of miRNAs that are expressed in very particular cell types and remain elusive. Sequencing allows us to quickly and accurately identify the expression of known miRNAs from small RNA-Seq data. The biogenesis of miRNAs leads to very specific characteristics observed in their sequences. In brief, miRNAs usually have a well-defined 5' end and a more flexible 3' end with the possibility of 3' tailing events, such as uridylation. Previous approaches to the prediction of novel miRNAs usually involve the analysis of structural features of miRNA precursor hairpin sequences obtained from genome sequence. We surmised that it may be possible to identify miRNAs by using these biogenesis features observed directly from sequenced reads, solely or in addition to structural analysis from genome data. To this end, we have developed mirnovo, a machine learning based algorithm, which is able to identify known and novel miRNAs in animals and plants directly from small RNA-Seq data, with or without a reference genome. This method performs comparably to existing tools, however is simpler to use with reduced run time. Its performance and accuracy has been tested on multiple datasets, including species with poorly assembled genomes, RNaseIII (Drosha and/or Dicer) deficient samples and single cells (at both embryonic and adult stage).

The taxonomic placement of three fossil Fundulus species and the timing of divergence within the North American topminnows (Teleostei: Fundulidae).

The fossils species †Fundulus detillae, †F. lariversi, and †F. nevadensis from localities in the western United States are represented by well-preserved material with date estimations. We combined morphological data for these fossil taxa with morphological and DNA-sequence data to conduct a phylogenetic analysis and a tip-based divergence-time estimation for the family Fundulidae. The resultant phylogeny is largely concordant with the prior total-evidence phylogeny. The fossil species do not form a monophyletic group, and do not represent a discrete western radiation of Fundulus as previously proposed. The genus Fundulus diverged into subgeneric clades likely in the Eocene or Oligocene (mean age 34.6 mya, 53-23 mya), and all subgeneric and most species-group clades had evolved by the middle Miocene. †Fundulus lariversi is a member of subgenus Fundulus in which all extant species are found only in eastern North America, demonstrating that fundulids had a complicated biogeographic history. We confirmed †Fundulus detillae as a member of the subgenus Plancterus. †F. nevadensis is not classified in a subgenus but likely is related to the subgenera Plancterus and Wileyichthys.

Transposon-driven transcription is a conserved feature of vertebrate spermatogenesis and transcript evolution.

Spermatogenesis is associated with major and unique changes to chromosomes and chromatin. Here, we sought to understand the impact of these changes on spermatogenic transcriptomes. We show that long terminal repeats (LTRs) of specific mouse endogenous retroviruses (ERVs) drive the expression of many long non-coding transcripts (lncRNA). This process occurs post-mitotically predominantly in spermatocytes and round spermatids. We demonstrate that this transposon-driven lncRNA expression is a conserved feature of vertebrate spermatogenesis. We propose that transposon promoters are a mechanism by which the genome can explore novel transcriptional substrates, increasing evolutionary plasticity and allowing for the genesis of novel coding and non-coding genes. Accordingly, we show that a small fraction of these novel ERV-driven transcripts encode short open reading frames that produce detectable peptides. Finally, we find that distinct ERV elements from the same subfamilies act as differentially activated promoters in a tissue-specific context. In summary, we demonstrate that LTRs can act as tissue-specific promoters and contribute to post-mitotic spermatogenic transcriptome diversity.

Large-scale analysis of microRNA expression, epi-transcriptomic features and biogenesis.

MicroRNAs are important genetic regulators in both animals and plants. They have a range of functions spanning development, differentiation, growth, metabolism and disease. The advent of next-generation sequencing technologies has made it a relatively straightforward task to detect these molecules and their relative expression via sequencing. There are a large number of published studies with deposited datasets. However, there are currently few resources that capitalize on these data to better understand the features, distribution and biogenesis of miRNAs. Herein, we focus on Human and Mouse for which the majority of data are available. We reanalyse sequencing data from 461 samples into a coordinated catalog of microRNA expression. We use this to perform large-scale analyses of miRNA function and biogenesis. These analyses include global expression comparison, co-expression of miRNA clusters and the prediction of miRNA strand-specificity and underlying constraints. Additionally, we report for the first time a global analysis of miRNA epi-transcriptomic modifications and assess their prevalence across tissues, samples and families. Finally, we report a list of potentially mis-annotated miRNAs in miRBase based on their aggregated modification profiles. The results have been collated into a comprehensive online repository of miRNA expression and features such as modifications and RNA editing events, which is available at: http://wwwdev.ebi.ac.uk/enright-dev/miratlas. We believe these findings will further contribute to our understanding of miRNA function in animals and benefit the miRNA community in general.

Evolution of Venomous Cartilaginous and Ray-Finned Fishes.

Venom and its associated delivery systems have evolved in numerous animal groups ranging from jellyfishes to spiders, lizards, shrews, and the male platypus. Building off new data and previously published anatomical and molecular studies, we explore the evolution of and variation within venomous fishes. We show the results of the first multi-locus, ordinal-level phylogenetic analysis of cartilaginous (Chondrichthyes) and ray-finned (Actinopterygii) fishes that hypothesizes 18 independent evolutions of this specialization. Ancestral-states reconstruction indicates that among the 2386-2962 extant venomous fishes, envenomed structures have evolved four times in cartilaginous fishes, once in eels (Anguilliformes), once in catfishes (Siluriformes), and 12 times in spiny-rayed fishes (Acanthomorpha). From our anatomical studies and phylogenetic reconstruction, we show that dorsal spines are the most common envenomed structures (∼95% of venomous fish species and 15 independent evolutions). In addition to envenomed spines, fishes have also evolved venomous fangs (2% of venomous fish species, two independent evolutions), cleithral spines (2% of venomous fish species, one independent evolution), and opercular or subopercular spines (1% of venomous fish species, three independent evolutions).

Repeated and Widespread Evolution of Bioluminescence in Marine Fishes.

Bioluminescence is primarily a marine phenomenon with 80% of metazoan bioluminescent genera occurring in the world's oceans. Here we show that bioluminescence has evolved repeatedly and is phylogenetically widespread across ray-finned fishes. We recover 27 independent evolutionary events of bioluminescence, all among marine fish lineages. This finding indicates that bioluminescence has evolved many more times than previously hypothesized across fishes and the tree of life. Our exploration of the macroevolutionary patterns of bioluminescent lineages indicates that the present day diversity of some inshore and deep-sea bioluminescent fish lineages that use bioluminescence for communication, feeding, and reproduction exhibit exceptional species richness given clade age. We show that exceptional species richness occurs particularly in deep-sea fishes with intrinsic bioluminescent systems and both shallow water and deep-sea lineages with luminescent systems used for communication.

Biofluorescence in Catsharks (Scyliorhinidae): Fundamental Description and Relevance for Elasmobranch Visual Ecology.

Biofluorescence has recently been found to be widespread in marine fishes, including sharks. Catsharks, such as the Swell Shark (Cephaloscyllium ventriosum) from the eastern Pacific and the Chain Catshark (Scyliorhinus retifer) from the western Atlantic, are known to exhibit bright green fluorescence. We examined the spectral sensitivity and visual characteristics of these reclusive sharks, while also considering the fluorescent properties of their skin. Spectral absorbance of the photoreceptor cells in these sharks revealed the presence of a single visual pigment in each species. Cephaloscyllium ventriosum exhibited a maximum absorbance of 484 ± 3 nm and an absorbance range at half maximum (λ1/2max) of 440-540 nm, whereas for S. retifer maximum absorbance was 488 ± 3 nm with the same absorbance range. Using the photoreceptor properties derived here, a "shark eye" camera was designed and developed that yielded contrast information on areas where fluorescence is anatomically distributed on the shark, as seen from other sharks' eyes of these two species. Phylogenetic investigations indicate that biofluorescence has evolved at least three times in cartilaginous fishes. The repeated evolution of biofluorescence in elasmobranchs, coupled with a visual adaptation to detect it; and evidence that biofluorescence creates greater luminosity contrast with the surrounding background, highlights the potential importance of biofluorescence in elasmobranch behavior and biology.

The first report of luminescent liver tissue in fishes: evolution and structure of bioluminescent organs in the deep-sea naked barracudinas (Aulopiformes: Lestidiidae).

Bioluminescent organs that provide ventral camouflage are common among fishes in the meso-bathypelagic zones of the deep sea. However, the anatomical structures that have been modified to produce light vary substantially among different groups of fishes. Although the anatomical structure and evolutionary derivation of some of these organs have been well studied, the light organs of the naked barracudinas have received little scientific attention. This study describes the anatomy and evolution of bioluminescent organs in the Lestidiidae (naked barracudinas) in the context of a new phylogeny of barracudinas and closely related alepisauroid fishes. Gross and histological examination of bioluminescent organs or homologous structures from preserved museum specimens indicate that the ventral light organ is derived from hepatopancreatic tissue and that the antorbital spot in Lestrolepis is, in fact, a second dermal light organ. In the context of the phylogeny generated from DNA-sequence data from eight gene fragments (7 nuclear and 1 mitochondrial), a complex liver with a narrow ventral strand running along the ventral midline evolves first in the Lestidiidae. The ventral hepatopancreatic tissue later evolves into a ventral bioluminescent organ in the ancestor of Lestidium and Lestrolepis with the lineage leading to the genus Lestrolepis evolving a dermal antorbital bioluminescent organ, likely for light-intensity matching. This is the first described hepatopancreatic bioluminescent organ in fishes.

Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells.

The idea that stem cell therapies work only via cell replacement is challenged by the observation of consistent intercellular molecule exchange between the graft and the host. Here we defined a mechanism of cellular signaling by which neural stem/precursor cells (NPCs) communicate with the microenvironment via extracellular vesicles (EVs), and we elucidated its molecular signature and function. We observed cytokine-regulated pathways that sort proteins and mRNAs into EVs. We described induction of interferon gamma (IFN-γ) pathway in NPCs exposed to proinflammatory cytokines that is mirrored in EVs. We showed that IFN-γ bound to EVs through Ifngr1 activates Stat1 in target cells. Finally, we demonstrated that endogenous Stat1 and Ifngr1 in target cells are indispensable to sustain the activation of Stat1 signaling by EV-associated IFN-γ/Ifngr1 complexes. Our study identifies a mechanism of cellular signaling regulated by EV-associated IFN-γ/Ifngr1 complexes, which grafted stem cells may use to communicate with the host immune system.

Species-specific bioluminescence facilitates speciation in the deep sea.

The vast darkness of the deep sea is an environment with few obvious genetic isolating barriers, and little is known regarding the macroevolutionary processes that have shaped present-day biodiversity in this habitat. Bioluminescence, the production and emission of light from a living organism through a chemical reaction, is thought to occur in approximately 80 % of the eukaryotic life that inhabits the deep sea (water depth greater than 200 m). In this study, we show, for the first time, that deep-sea fishes that possess species-specific bioluminescent structures (e.g., lanternfishes, dragonfishes) are diversifying into new species at a more rapid rate than deep-sea fishes that utilize bioluminescence in ways that would not promote isolation of populations (e.g., camouflage, predation). This work adds to our understanding of how life thrives and evolution shaped present-day biodiversity in the deep sea, the largest and arguably least explored habitat on earth.