Xenopus () (from Greek ξενος, xenos 'strange' + πους, pous 'foot', commonly known as the clawed frog) is a genus of highly aquatic frogs native to sub-Saharan Africa. Twenty species are currently described within it. The two best-known species of this genus are Xenopus laevis and Xenopus tropicalis, which are commonly studied as model organisms for developmental biology, cell biology, toxicology, neuroscience and for modelling human disease and birth defects.
The genus is also known for its allopolyploidy, with some species having up to 12 sets of chromosomes (all have undergone diploidization; the highest is ).
Characteristics
Xenopus laevis is a rather inactive creature. It is incredibly hearty and can live up to 15 years. At times the ponds that Xenopus laevis is found in dry up, compelling it, in the dry season, to burrow into the mud, leaving a tunnel for air. It may lie dormant for up to a year. If the pond dries up in the rainy season, Xenopus laevis may migrate long distances to another pond, maintaining hydration by the rains. It is an adept swimmer, swimming in all directions with ease. It is barely able to hop, but it is able to crawl. It spends most of its time underwater and comes to surface to breathe. Respiration is predominantly through its well-developed lungs; there is little cutaneous respiration.
Description
All species of Xenopus have flattened, somewhat egg-shaped and streamlined bodies, and very slippery skin (because of a protective mucus covering). The frog's skin is smooth, but with a lateral line sensory organ that has a stitch-like appearance. The frogs are all excellent swimmers and have powerful, fully webbed toes, though the fingers lack webbing. Three of the toes on each foot have conspicuous black claws.
The frog's eyes are on top of the head, looking upwards. The pupils are circular. They have no moveable eyelids, tongues (rather it is completely attached to the floor of the mouth) or eardrums (similarly to Pipa pipa, the common Suriname toad).
Unlike most amphibians, they have no haptoglobin in their blood.
Behaviour Xenopus species are entirely aquatic, though they have been observed migrating on land to nearby bodies of water during times of drought or in heavy rain. They are usually found in lakes, rivers, swamps, potholes in streams, and man-made reservoirs.
Adult frogs are usually both predators and scavengers, and since their tongues are unusable, the frogs use their small fore limbs to aid in the feeding process. Since they also lack vocal sacs, they make clicks (brief pulses of sound) underwater (again similar to Pipa pipa). Males establish a hierarchy of social dominance in which primarily one male has the right to make the advertisement call. The females of many species produce a release call, and Xenopus laevis females produce an additional call when sexually receptive and soon to lay eggs. The Xenopus species are also active during the twilight (or crepuscular) hours.
During breeding season, the males develop ridge-like nuptial pads (black in color) on their fingers to aid in grasping the female. The frogs' mating embrace is inguinal, meaning the male grasps the female around her waist.
Species
Extant species
Xenopus allofraseri Xenopus amieti (volcano clawed frog) Xenopus andrei (Andre's clawed frog) Xenopus borealis (Marsabit clawed frog) Xenopus boumbaensis (Mawa clawed frog) Xenopus calcaratus Xenopus clivii (Eritrea clawed frog) Xenopus epitropicalis (Cameroon clawed frog) Xenopus eysoole Xenopus fischbergi Xenopus fraseri (Fraser's platanna) Xenopus gilli (Cape platanna) Xenopus itombwensis Xenopus kobeli Xenopus laevis (African clawed frog or common platanna) Xenopus largeni (Largen's clawed frog) Xenopus lenduensis (Lendu Plateau clawed frog) Xenopus longipes (Lake Oku clawed frog) Xenopus mellotropicalis Xenopus muelleri (Müller's platanna) Xenopus parafraseri Xenopus petersii (Peters' platanna) Xenopus poweri Xenopus pygmaeus (Bouchia clawed frog) Xenopus ruwenzoriensis (Uganda clawed frog) Xenopus tropicalis (western clawed frog) Xenopus vestitus (Kivu clawed frog) Xenopus victorianus (Lake Victoria clawed frog) Xenopus wittei (De Witte's clawed frog)
Fossil species The following fossil species have been described:[ Xenopus] at Fossilworks.org †Xenopus arabiensis - Oligocene Yemen Volcanic Group, Yemen †Xenopus hasaunus †Xenopus romeri - Itaboraian Itaboraí Formation, Brazil †Xenopus stromeri cf. Xenopus sp. - Campanian - Los Alamitos Formation, Argentina Xenopus (Xenopus) sp. - Late Oligocene Nsungwe Formation, Tanzania Xenopus sp. - Miocene Morocco Xenopus sp. - Early Pleistocene Olduvai Formation, Tanzania
There are also numerous "molecular fossil" species known today only as extinct parents of living allopolyploid species.
Model organism for biological research Like many other frogs, they are often used in laboratory as research subjects. Xenopus embryos and eggs are a popular model system for a wide variety of biological studies. This animal is used because of its powerful combination of experimental tractability and close evolutionary relationship with humans, at least compared to many model organisms.
Xenopus has long been an important tool for in vivo studies in molecular, cell, and developmental biology of vertebrate animals. However, the wide breadth of Xenopus research stems from the additional fact that cell-free extracts made from Xenopus are a premier in vitro system for studies of fundamental aspects of cell and molecular biology. Thus, Xenopus is a vertebrate model system that allows for high-throughput in vivo analyses of gene function and high-throughput biochemistry. Furthermore, Xenopus oocytes are a leading system for studies of ion transport and channel physiology. Xenopus is also a unique system for analyses of genome evolution (espcially allopolyploidization and diploidization) in vertebrates, as different Xenopus species form a allo-ploidy series (2x, 4x, 8x, 12x) formed by interspecific hybridization. (For an overview of Xenopus phylogeny taking into account past hybridization events, see Figure 3 of Evans et al., 2015.)
In 1931, Lancelot Hogben noted that Xenopus laevis females ovulated when injected with the urine of pregnant women. This led to a pregnancy test that was later refined by South African researchers Hillel Abbe Shapiro and Harry Zwarenstein. A female Xenopus frog injected with a woman's urine was put in a jar with a little water. If eggs were in the water a day later it meant the woman was pregnant. Four years after the first Xenopus test, Zwarenstein's colleague, Dr Louis Bosman, reported that the test was accurate in more than 99% of cases.Diagnosis of Pregnancy, Louis P. Bosman, British Medical Journal 1937;2:939, 6 November 1937 From the 1930s to the 1950s, thousands of frogs were exported across the world for use in these pregnancy tests.
The of the Marine Biological Laboratory is an in vivo repository for transgenic and mutant strains and a training center.
Online Model Organism Database Xenbase is the Model Organism Database (MOD) for both Xenopus laevis and Xenopus tropicalis.
Investigation of human disease genes
All modes of Xenopus research (embryos, cell-free extracts, and oocytes) are commonly used in direct studies of human disease genes and to study the basic science underlying initiation and progression of cancer. Xenopus embryos for in vivo studies of human disease gene function: Xenopus embryos are large and easily manipulated, and moreover, thousands of embryos can be obtained in a single day. Indeed, Xenopus was the first vertebrate animal for which methods were developed to allow rapid analysis of gene function using misexpression (by mRNA injection). Injection of mRNA in Xenopus that led to the cloning of interferon. Moreover, the use of morpholino-antisense oligonucleotides for gene knockdowns in vertebrate embryos, which is now widely used, was first developed by Janet Heasman using Xenopus.
In recent years, these approaches have played in important role in studies of human disease genes. The mechanism of action for several genes mutated in human cystic kidney disorders (e.g. nephronophthisis) have been extensively studied in Xenopus embryos, shedding new light on the link between these disorders, ciliogenesis and Wnt signaling. Xenopus embryos have also provided a rapid test bed for validating newly discovered disease genes. For example, studies in Xenopus confirmed and elucidated the role of PYCR1 in cutis laxa with progeroid features.
Transgenic Xenopus for studying transcriptional regulation of human disease genes: Xenopus embryos develop rapidly, so transgenesis in Xenopus is a rapid and effective method for analyzing genomic regulatory sequences. In a recent study, mutations in the SMAD7 locus were revealed to associate with human colorectal cancer. The mutations lay in conserved, but noncoding sequences, suggesting these mutations impacted the patterns of SMAD7 transcription. To test this hypothesis, the authors used Xenopus transgenesis, and revealed this genomic region drove expression of GFP in the hindgut. Moreover, transgenics made with the mutant version of this region displayed substantially less expression in the hindgut.
Xenopus cell-free extracts for biochemical studies of proteins encoded by human disease genes: A unique advantage of the Xenopus system is that cytosolic extracts contain both soluble cytoplasmic and nuclear proteins (including chromatin proteins). This is in contrast to cellular extracts prepared from somatic cells with already distinct cellular compartments. Xenopus egg extracts have provided numerous insights into the basic biology of cells with particular impact on cell division and the DNA transactions associated with it (see below).
Studies in Xenopus egg extracts have also yielded critical insights into the mechanism of action of human disease genes associated with genetic instability and elevated cancer risk, such as ataxia telangiectasia, BRCA1 inherited breast and ovarian cancer, Nbs1 Nijmegen breakage syndrome, RecQL4 Rothmund-Thomson syndrome, c-Myc oncogene and FANC proteins (Fanconi anemia).
Xenopus oocytes for studies of gene expression and channel activity related to human disease: Yet another strength of Xenopus is the ability to rapidly and easily assay the activity of channel and transporter proteins using expression in oocytes. This application has also led to important insights into human disease, including studies related to trypanosome transmission, Epilepsy with ataxia and sensorineural deafness Catastrophic cardiac arrhythmia (Long-QT syndrome) and Megalencephalic leukoencephalopathy.
Gene editing by the CRISPR/CAS system has recently been demonstrated in Xenopus tropicalis and Xenopus laevis. This technique is being used to screen the effects of human disease genes in Xenopus and the system is sufficiently efficient to study the effects within the same embryos that have been manipulated.
Investigation of fundamental biological processes
Signal transduction: Xenopus embryos and cell-free extracts are widely used for basic research in signal transduction. In just the last few years, Xenopus embryos have provided crucial insights into the mechanisms of TGF-beta and Wnt signal transduction. For example, Xenopus embryos were used to identify the enzymes that control ubiquitination of Smad4, and to demonstrate direct links between TGF-beta superfamily signaling pathways and other important networks, such as the MAP kinase pathway and the Wnt pathway. Moreover, new methods using egg extracts revealed novel, important targets of the Wnt/GSK3 destruction complex.