In this experiment, labeled cells appeared in the retinal growth zones in both surface fish and cavefish during the BrdU pulse but could only be detected during the chase in surface fish. The results of these crosses show that eye degeneration is a multi-factorial trait. McCauley DW, Hixon E, Jeffery WR. The close phylogenetic relationship between Astyanax and zebrafish permits molecular techniques and resources to be shared between the two species. One is its very large size (36), which might be expected to render it a more frequent target for mutation. Pie: Piedras. Yamamoto Y, Byerly MS, Jackman WR, Jeffery WR. In addition, some genes could be mutated and directly affect eye development, whereas other genes could act downstream of the mutated genes and changes in their expression could indirectly mediate eye degeneration. Phylogenetic analysis using DNA sequences has been the major approach used to determine the relationships between cavefish populations. Second, some cavefish populations, including some of those with albinism, have also accumulated different mutations in the Mc1r gene causing reduced numbers of melanophores and melanin pigmentation due to defective MSH signaling. National Library of Medicine Thus, as in the case of eyes, different cavefish populations have distinctive melanophore and melanin phenotypes, supporting multiple independent origins of regressed pigmentation. RS: Ro Subterrneo. For example, shh is known to have possible effects on taste bud and forebrain development, which are enhanced in cavefish, as well as negative effects on eye development (32, 46, 67, 69). Evolution of pigment cell regression in the cavefish, Menuet A, Alunni A, Joly J-S, Jeffery WR, Rtaux S. Shh overexpression in, Mitchell RW, Russell WH, Elliot WR. As in all QTL studies, the challenge is to find the relevant gene(s) within the identified QTL. Inset: Mexico showing the northeastern region indicated in the sketch map (shaded rectangle) and the outlying Guerrero population (shaded sphere). Genetics of hair and skin color. Cavefish tyrosinase-positive albinism. For example, expression of the major eye regulatory gene pax6 is changed in Pachn, Los Sabinos, and Curva cavefish (56). Astyanax and zebrafish have the same chromosome number (2N = 50) and share extensive blocks of syntenic DNA sequences throughout their genomes. (c) Cave isopod, Monolistra bolei. A novel role for Mc1r in the parallel evolution of depigmentation in independent populations of the cavefish. (e, f) from Strickler et al. In contrast, the F2 generation shows a variety of eye sizes, ranging from nearly normal to almost as completely reduced as those of cavefish. Bottom. Ro Subterrneo cavefish, along with two other populations, are referred to as the Micos cluster. Central role for the lens in cavefish eye degeneration. about navigating our updated article layout. Pax6 directs optic cup development, whereas Pax2 and Vax1 control optic stalk development. The oca2 gene appears to be responsible for loss of melanin pigment in two cavefish populations, but the mutations are distinct, implying that Pachn and Molino evolved the albinism phenotype independently. The arrest in cavefish eye growth is probably a consequence of the dysfunction of a crucial regulatory component(s) in the developing eye. Thus, melanophore reduction is not due to the absence of pigment cell precursors or effects on their ability to select the proper migration pathway. First, surface fish colonized (or were entrapped in) caves, and their differential survival led to the formation of cave-adapted populations in which regressive evolution could have been initiated. Therefore, it is still possible that changes in their protein sequence might lead to altered functions and contribute to eye degeneration. (a) A Ro Subterrneo x Pachn F1 hybrid with large external eyes. and transmitted securely. (2002). (2003). Apoptosis was detected in several different eye tissues (Figure 5c,d). These genes could be regulatory genes functioning at or near the beginning of eye developmental pathways, subsidiary genes of various sorts within the framework of the pathways, or genes encoding enzymes or structural proteins that function at or near the end of the pathways. (a) Cave planarian. TPC: tyrosinase positive cells (melanophores). (b,d) Lens transplant side. will also be available for a limited time. Transplanted lenses behave autonomously: The cavefish lens died on schedule in the surface fish host, and the surface fish lens survived and grew in the cavefish host. The benefits of eye loss in the cave environment are also still a mystery but some reasonable ideas have been suggested. Evidence for multiple genetic lineages with similar eyeless phenotypes in the blind cavefish. Lens transplantation. (2003). Later, retinal and RPE (retinal pigment epithelium) cells also undergo apoptosis (58). A diverse group of animals, including members of most major phyla, have adapted to life in the perpetual darkness of caves. An anchored linkage map reveals eye and pigment candidate genes in Astyanax QTL and corresponding syntenic regions in Danio (zebrafish). It should be emphasized that the current data does not allow us to conclude unequivocally that either selection or neutral mutation is responsible for regressive evolution. The Astyanax surface fish Mc1r allele rescued pigmentation, but neither of the cavefish mutant alleles did so, suggesting that these changes account for loss of function in the two cavefish populations. HHS Vulnerability Disclosure, Help Another idea is that the genes involved in eye development are pleiotropic and have selectable effects on constructive traits. The Mc1r gene encodes a receptor for the melanogenesis regulating ligand MSH (45). Moritz OL, Molday RS.

The albinism gene is. A gene for mouse. Thus, a phenocopy of blind cavefish can be obtained in surface fish by increasing the levels of shh gene expression, demonstrating the key role for Shh signaling in eye degeneration. Surface fish larvae that developed from embryos with elevated Shh levels were missing an eye on one side of the head. In surface fish embryos, pax6 expression domains in the bilateral optic fields connect across the midline. From Yamamoto and Jeffery (2000) and Jeffery et al. (fj) Transplantation of a Pachn (g,h) or Los Sabinos (i, j) embryonic lens into the optic cup of a surface fish embryo after its own lens is removed causes retardation of eye development in adults. The .gov means its official. The molecular and cellular mechanisms of eye degeneration have been studied most extensively in Pachn cavefish. government site.

Sadoglu P, McKee A.

The spheres indicate the approximate position of caves with Astyanax cavefish. The next frontier in cavefish research will be to identify more of the genes and mutations involved in regressive evolution, especially those controlling the loss of eyes and reduction of melanophores, and from this information learn more about the forces that drove the evolution of these regressive phenotypes during adaptation of cavefish to perpetual darkness. This raises the possibility that some genes at the termini of development pathways may be affected during eye regression in Astyanax. To determine the identity of the brown locus within the QTL, the relevant Astyanax linkage group was anchored to the zebrafish physical genome, and a candidate gene approach based on genes with known melanogenic activity was applied. If so, this resembles tail loss in anural ascidian larvae, another well-known case of regressive evolution, in which muscle actin structural genes become nonfunctional via mutations in their coding regions, but earlier-expressed regulatory genes are still functional (28). Fairbank PD, Lee C, Ellis A, Hildebrand JD, Gross JM, Wallingford JB. The final phenotypes are similar (although not identical), suggesting that there are many different ways to produce the same phenotypes. Both mapping procedures identified multiple quantitative trait loci (QTL) for eye loss: three QTL from the RAPD analysis and 12 QTL from the more sensitive microsatellite analysis. Rasquin P. Progressive pigmentary regression in fishes associated with cave environments. Evolution of color patterns. Genetic analysis has shown that the regression in eyes and pigmentation occur independently (61), and thus these two recessive traits could be controlled by different evolutionary mechanisms. Retinal development is known to be dependent on a functional lens in teleosts (27), but the underlying mechanisms are poorly understood. Thus, a normal lens appears to protect the retina from apoptosis and sustain its growth. Dorsal views of the anterior neural plate showing shhA expression (blue) compared with dlx3, pax6, and pax2a markers. For example, the restoration of eyes by lens transplantation suggests that genes operating downstream of lens function are present and potentially active in cavefish (23, 66). Why is this?

Similar to eyes, in some cases complementation tests result in F1 hybrids with greater pigmentation (61, 64), which is suggestive of different genes, whereas in others there is noncomplementation, indicating that the same genes are involved (40, 64) (Figure 7c,d). There are no significant differences in the coding sequences of cavefish and surface fish A-crystallin (4), implying that the relevant mutation may be in a regulatory region. Thus, melanogenesis appears to be blocked at the step in which L-tyrosine is transferred into the melanosome. Thus, in studying the evolution of cave animals, the mechanism of trait loss can be directly linked to the environmental conditions that have produced it. The subject of this review, the cavefish Astyanax mexicanus, is one of the few cave animals that can be maintained and propagated in the laboratory (65). The shhA and shhB midline expression domains are expanded in Pachn, Chica, and Los Sabinos cavefish relative to surface fish (see Figure 8a,b for shhA in Pachn). Because of this deletion, the Pachn OCA2 protein would contain only a part of intron 23 and lack most of exon 24 (Figure 11). Thus, many different genes control eye degeneration. Cu: Curva. Nonetheless, the DNA sequence studies suggest at least two origins for Astyanax cavefish in northeastern Mexico, one in the Micos cluster and at least one other in the El Abra cluster, although this is likely a minimal estimate. For example, in the case of albinism it might be advantageous to block melanin formation at the level of L-tyrosine conversion to L-DOPA because this could shunt more L- tyrosine substrate into the branch pathway in which specialized neural cells produce the neural transmitter L-dopamine (Figure 10a), a possible prerequisite for behavioral changes in cavefish. The Guatemala, El Abra, and Micos clusters are indicated on the map. In contrast, the expression of some genes are changed in cavefish relative to surface fish. Yamamoto Y, Jeffery WR. It can be raised on a simple diet, spawns frequently and abundantly, and has a generation time of approximately 4 to 6 months. When shhA mRNA was injected into one side of a cleaving embryo, pax6 expression was downregulated in the corresponding optic field. Unfortunately, this is not the case. The wider gap between pax6-expressing optic fields in the cavefish neural plate provides a clue as to how eye degeneration might be controlled. (a) A summary of steps in which L-tyrosine is converted to melanin in the melanosome and dopamine in the cytoplasm showing the key roles of tyrosinase, other enzymes, and the presumed role of OCA2 as an L-tyrosine transporter. There are two major competing hypotheses to explain regressive evolution in Astyanax cavefish and other cave animals (9). Accordingly, linkage analysis in surface fish x Pachn or Molino pedigrees located a single albinism QTL(oca2) on the Astyanax microsatellite map (40) (Figure 9b). Genetic complementation analysis also supports multiple independent origins of cavefish populations and their regressive phenotypes. Genetic linkage analysis has identified 12 QTL that are directly involved in eye degeneration. Cavefish can be compared with their surface fish con-specifics in the same way mutants are compared with wild-type phenotypes. Second, the established cavefish populations spread horizontally and vertically underground, in some cases for relatively long distances, whilst continuing regressive evolution. Jeffery WR, Martasian DP. (c) From Protas et al. Yamamoto Y, Stock DW, Jeffery WR. The feature that makes Astyanax the white rat of cave animals is its suitability as a laboratory animal. To do this, the Astyanax microsatellite map was anchored to the zebrafish physical map (16). Our understanding of the evolutionary history of regressive traits comes from two kinds of data: (a) morphological comparisons between the various cavefish populations and (b) genetics. Rees JL. The https:// ensures that you are connecting to the The same defects are seen in Chica, Tinaja, Curva, and Los Sabinos cavefish (23). Therefore, Mc1r is another example of a single gene that is repeatedly targeted by different mutations to change a complex phenotype during parallel or convergent evolution.

For oca2, the answer may be related to properties of the gene itself or its potentially restricted function in melanogenesis. Members of the Micos cluster have more intense pigmentation than members of the El Abra and Guatemala clusters, some of which have evolved albinism (49). Just as remarkable are the convergent phenotypes that have evolved in these animals, namely the loss of eyes and pigmentation. These changes in the optic cup have impacts later in development, as evidenced by a degree of independence between lens and retinal degeneration in some cavefish populations (61, 62). Astyanax has three types of pigment cells: black melanophores, silver iridophores, and orange xanthophores. Thus, one of the most interesting questions in the evolutionary biology of cave animals is whether natural selection has a role in the evolution of regressive traits, and if not, what are the alternatives? In these experiments, a surface fish lens was transplanted into the Pachn or Los Sabinos optic cup, and reciprocally, a cavefish lens was transplanted into the surface fish optic cup. However, the embryonic lens starts to die several days before any other eye tissue, earmarking it for a possible regulatory role (21, 58). Sadoglu P. Mendelian inheritance in hybrids between the Mexican blind fish and their overground ancestors. A second gene that affects eye and body color in Mexican blind cavefish. The fact that Astyanax cavefish can arise independently is not surprising considering 86 cavefish species have been described in 19 teleost families (43). Thus, cavefish lens apoptosis may be controlled by the activation of proapoptotic factors and suppression of antiapoptotic factors. Importantly, lens apoptosis was also induced by shh overexpression in surface fish embryos (67). Early genetic studies showed that albinism is controlled by a single recessive gene in Pachn cavefish (49). The mechanisms of regressive evolution are poorly understood. Department of Biology, University of Maryland, College Park, Maryland 20742; eye degeneration, loss of pigmentation, albinism, development, genetics, Alunni A, Menuet A, Candal E, Pnigault J-B, Jeffery WR, Rtaux S. Developmental mechanisms for retinal degeneration in the blind cavefish, Behrens M, Wilkens H, Schmale H. Cloning of the A-crystallin genes of the blind cave form and the epigean form of. Comparative optic development in. Ja: Japons (albino). Cahn PH.

The lens controls cell survival in the retina: evidence from the blind cavefish.