In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for ...improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research.
Sexual dimorphism is one of the most pervasive and diverse features of animal morphology, physiology, and behavior. Despite the generality of the phenomenon itself, the mechanisms controlling how sex ...is determined differ considerably among various organismic groups, have evolved repeatedly and independently, and the underlying molecular pathways can change quickly during evolution. Even within closely related groups of organisms for which the development of gonads on the morphological, histological, and cell biological level is undistinguishable, the molecular control and the regulation of the factors involved in sex determination and gonad differentiation can be substantially different. The biological meaning of the high molecular plasticity of an otherwise common developmental program is unknown. While comparative studies suggest that the downstream effectors of sex‐determining pathways tend to be more stable than the triggering mechanisms at the top, it is still unclear how conserved the downstream networks are and how all components work together. After many years of stasis, when the molecular basis of sex determination was amenable only in the few classical model organisms (fly, worm, mouse), recently, sex‐determining genes from several animal species have been identified and new studies have elucidated some novel regulatory interactions and biological functions of the downstream network, particularly in vertebrates. These data have considerably changed our classical perception of a simple linear developmental cascade that makes the decision for the embryo to develop as male or female, and how it evolves.
This review assesses recent insight into the molecular mechanisms and plasticity of sex determination and their evolution across a wide range of species.
A plethora of corroborative genetic studies led to the view that, across the animal kingdom, the gene-regulatory cascades triggering sexual development bear little resemblance to each other. As a ...result, the common emerging picture is that the genes at the top of the cascade are not conserved, whereas the downstream genes have homologues in a much broader spectrum of species. Among these downstream effectors, a gene family involved in sex differentiation in organisms as phylogenetically divergent as corals, Caenorhabditis elegans, Drosophila, frogs, fish, birds and mammals is the dmrt gene family. Despite the attention that Dmrt1 factors have received, to date it has not been elucidated how Dmrt1s mediate their activities and putative downstream targets have yet to be characterized. However, a remarkable amount of descriptive expression data has been gathered in a large variety of fish, particularly with respect to early gonadal differentiation and sex change. This minireview aims at distilling the current knowledge of fish dmrt1s, in terms of expression and regulation. It is shown how gonadal identities correlate with dimorphic dmrt1 expression in gonochoristic and hermaphroditic fish species. It is also described how sex steroid hormones affect gonadal identity and dmrt1 expression. Emphasis is also given to recent findings dealing with transcriptional, post-transcriptional, post-translational and functional regulations of the dmrt1a/dmrt1bY gene pair in medaka.
Lessons from an unusual vertebrate sex-determining gene Bertho, Sylvain; Herpin, Amaury; Schartl, Manfred ...
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
08/2021, Letnik:
376, Številka:
1832
Journal Article
Recenzirano
Odprti dostop
So far, very few sex-determining genes have been identified in vertebrates and most of them, the so-called ‘usual suspects’, evolved from genes which fulfil essential functions during sexual ...development and are thus already tightly linked to the process that they now govern. The single exception to this ‘usual suspects’ rule in vertebrates so far is the conserved salmonid sex-determining gene,
sdY
(sexually dimorphic on the Y chromosome), that evolved from a gene known to be involved in regulation of the immune response. It is contained in a jumping sex locus that has been transposed or translocated into different ancestral autosomes during the evolution of salmonids. This special feature of
sdY
, i.e. being inserted in a ‘jumping sex locus’, could explain how salmonid sex chromosomes remain young and undifferentiated to escape degeneration. Recent knowledge on the mechanism of action of
sdY
demonstrates that it triggers its sex-determining action by deregulating oestrogen synthesis that is a conserved and crucial pathway for ovarian differentiation in vertebrates. This result suggests that
sdY
has evolved to cope with a pre-existing sex differentiation regulatory network. Therefore, ‘limited options’ for the emergence of new master sex-determining genes could be more constrained by their need to tightly interact with a conserved sex differentiation regulatory network rather than by being themselves ‘usual suspects’, already inside this sex regulatory network.
This article is part of the theme issue ‘Challenging the paradigm in sex chromosome evolution: empirical and theoretical insights with a focus on vertebrates (Part I)’.
Platyfish and swordtails of the genus Xiphophorus provide a well-established model for melanoma research and have become well known for this feature. Recently, modelling approaches for other human ...diseases in Xiphophorus have been developed or are emerging. This Review provides a comprehensive summary of these models and discusses how findings from basic biological and molecular studies and their translation to medical research demonstrate that Xiphophorus models have face, construct and predictive validity for studying a broad array of human diseases. These models can thus improve our understanding of disease mechanisms to benefit patients.
The Y and W chromosomes of mammals and birds are known to be small because most of their genetic content degenerated and were lost due to absence of recombination with the X or Z, respectively. Thus, ...a picture has emerged of ever-shrinking Ys and Ws that may finally even fade into disappearance. We review here the large amount of literature on sex chromosomes in vertebrate species and find by taking a closer look, particularly at the sex chromosomes of fishes, amphibians and reptiles where several groups have evolutionary younger chromosomes than those of mammals and birds, that the perception of sex chromosomes being doomed to size reduction is incomplete. Here, sex-determining mechanisms show a high turnover and new sex chromosomes appear repeatedly. In many species, Ys and Ws are larger than their X and Z counterparts. This brings up intriguing perspectives regarding the evolutionary dynamics of sex chromosomes. It can be concluded that, due to accumulation of repetitive DNA and transposons, the Y and W chromosomes can increase in size during the initial phase of their differentiation.
Lungfishes belong to lobe-fined fish (Sarcopterygii) that, in the Devonian period, 'conquered' the land and ultimately gave rise to all land vertebrates, including humans
. Here we determine the ...chromosome-quality genome of the Australian lungfish (Neoceratodus forsteri), which is known to have the largest genome of any animal. The vast size of this genome, which is about 14× larger than that of humans, is attributable mostly to huge intergenic regions and introns with high repeat content (around 90%), the components of which resemble those of tetrapods (comprising mainly long interspersed nuclear elements) more than they do those of ray-finned fish. The lungfish genome continues to expand independently (its transposable elements are still active), through mechanisms different to those of the enormous genomes of salamanders. The 17 fully assembled lungfish macrochromosomes maintain synteny to other vertebrate chromosomes, and all microchromosomes maintain conserved ancient homology with the ancestral vertebrate karyotype. Our phylogenomic analyses confirm previous reports that lungfish occupy a key evolutionary position as the closest living relatives to tetrapods
, underscoring the importance of lungfish for understanding innovations associated with terrestrialization. Lungfish preadaptations to living on land include the gain of limb-like expression in developmental genes such as hoxc13 and sall1 in their lobed fins. Increased rates of evolution and the duplication of genes associated with obligate air-breathing, such as lung surfactants and the expansion of odorant receptor gene families (which encode proteins involved in detecting airborne odours), contribute to the tetrapod-like biology of lungfishes. These findings advance our understanding of this major transition during vertebrate evolution.
Flatfish are unique amongst fishes because of their extreme asymmetric body shape with both eyes on the upside and full depigmentation on the bottom side. During metamorphosis a primarily bilateral ...symmetric larvae turns into the flat adult body. Analysis of the whole genome sequence of the Japanese flounder revealed that retinoic acid signalling is critically involved in several processes that underlie the morphogenetic changes during metamorphosis.
PDF
