Fish Fend Off Invading Germs With An Initial Response Similar To One Found In Humans

Since the human response to infection is highly complex, research to understand how people fight infection is facilitated by studying how similar processes occur in simpler organisms. Zebrafish are becoming an important model for human disease, since they are easily handled, maintained and manipulated and many fundamental processes between zebrafish and humans are conserved. In addition, the small zebrafish embryo is highly amenable to drug screening assays.

The functional similarity between the initial responses of zebrafish embryo and humans to infection suggests that the zebrafish embryo may be a valuable model for understanding early immune responses and identifying potential therapeutics for infection or immune mediated disease. However, the initial response of zebrafish to infection and how it compares to the human response is not well understood.
When humans first encounter germs, like viruses or bacteria, the first stage of a two-part inflammatory response is triggered, which is termed the innate immune response. During this early phase, proteins are made around the site of infection to initiate the body's defense system and to recruit circulating immune cells, which begins the inflammatory process. A family of proteins that are critical to instigating the immune response are the interferons (IFN), particularly IFN-γ.
Scientists now report that IFN-γ is also produced in zebrafish embryos when they are exposed to bacteria that cause disease in fish. These studies use developing zebrafish embryos whose response to infection is isolated to the innate immune response. Since the zebrafish embryo only demonstrates innate immunity, it allows for specific study of the effects of IFN-γ on these early events. This study demonstrates that both zebrafish and human IFN-γ proteins function in much the same way, despite having very distinct protein structures. In both zebrafish and humans, IFN-γ triggers the production of an array of proteins that rally the defense mechanisms of the infected cell and activate the immune system. They also found that compromising the ability of the zebrafish embryos to produce IFN-γ impairs the fish's ability to survive infection. Thus, the zebrafish embryo may provide a very simple model to understand the innate immune response.
Interestingly, large quantities of bacteria, which would cause septic shock -- a potentially fatal condition -- in humans, do not elicit the same response in zebrafish. This suggests that some key differences between the immune systems of zebrafish and humans may also provide insight into harmful events associated with inflammation.
The characterization of IFN-γ function in zebrafish is presented in an article appearing in the November/December 2009 issue of the new research journal, Disease Models & Mechanisms (DMM), published by The Company of Biologists, a non-profit based in Cambridge, UK.
Journal reference:
Dirk Sieger, Cornelia, David Neifer, Maria Leptin, Astrid van der Sar. The role of gamma interferon in innate immunity in the zebrafish embryo. Disease Models & Mechanisms, November/December 2009 DOI: http://dmm.biologists.org/
Adapted from materials provided by The Company of Biologists, via EurekAlert!, a service of AAAS.

Mutated Gene In Zebrafish Sheds Light On Blindness In Humans

Among zebrafish, the eyes have it. Inside them is a mosaic of light-sensitive cells whose structure and functions are nearly identical to those of humans. There, biologists at The Florida State University discovered a gene mutation that determines if the cells develop as rods (the photoreceptors responsible for dim-light vision) or as cones (the photoreceptors needed for color vision).Described in a paper published in the Proceedings of the National Academy of Sciences (PNAS), the landmark study of retinal development in zebrafish larvae and the genetic switch it has identified should shed new light on the molecular mechanisms underlying that development and, consequently, provide needed insight on inherited retinal diseases in humans.>From FSU's Department of Biological Science and Program in Neuroscience, doctoral candidate Karen Alvarez-Delfin (first author of the PNAS paper), postdoctoral fellow Ann Morris (second author), and Associate Professor James M. Fadool are the first scientists to identify the crucial function of a previously known gene called "tbx2b." The researchers have named the newfound allele (a different form of a gene) "lor" -- for "lots-of-rods" -- because the mutation results in too many rods and fewer ultraviolet cones than in the normal eye."Our goal is to generate animal models of inherited diseases of the eye and retina to understand the progression of disease and find more effective treatments for blindness," said Fadool, faculty advisor to Alvarez-Delfin and principal investigator for Morris's ongoing research. "We are excited about the mutation that Karen has identified because it is one of the few mutations in this clinically critical pathway that is responsible for cells developing into one photoreceptor subtype rather than another.""What is striking in this case is that the photoreceptor cell changes we observed in the retinas of zebrafish are opposite to the changes identified in Enhanced S-cone syndrome (ESCS), an inherited human retinal dystrophy in which the rods express genes usually only found in cones, eventually leading to blindness," Alvarez-Delfin said. "Equally surprising is that this study and others from our lab show that while alterations in photoreceptor development in the human and mouse eyes lead to retinal degeneration and blindness, they don't in zebrafish. Therefore, the work from our Florida State lab and with our collaborators at the University of Pennsylvania, Vanderbilt University and the University of Louisville should provide a model for better understanding the differences in outcomes between mammals and fish, and why the human mutation leads to degenerative disease."Morris calls the zebrafish an ideal genetic model for studies of development and disease. The common aquarium species are vertebrates, like humans. Their retinal organization and cell types are similar to those in humans. Zebrafish mature rapidly, and lay many eggs. The embryos are transparent, and they develop externally, unlike mammals, which develop in utero."This lets us study developmental processes such as the formation of tissues and organs in living animals," she said."From a developmental biology perspective, our research will help us unravel the competing signals necessary for generating the different photoreceptor cell types in their appropriate numbers and arrangement," Morris said. "The highly specialized nature of rods and cones may make them particularly vulnerable to inherited diseases and environmental damage in humans. Understanding the genetic processes of photoreceptor development could lead to clinical treatments for the millions of people affected by photoreceptor cell dystrophies such as retinitis pigmentosa and macular degeneration."The mosaic arrangement of photoreceptors in fish was first described more than 100 years ago, but the J. Fadool laboratory at Florida State was the first to successfully take advantage of the pattern to identify mutations affecting photoreceptor development and degeneration."Imagine a tile mosaic," Fadool said. "That is the kind of geometric pattern formed by the rod and cone photoreceptors in the zebrafish retina. This mosaic is similar to the pattern of a checkerboard but with four colors rather than two alternating in a square pattern. The red-, green-, blue-, and ultraviolet-sensitive cones are always arranged in a precise repeating pattern. Human retinas have a photoreceptor mosaic, too, but here the term is used loosely, because while the arrangement of the different photoreceptors is nonrandom, they don't form the geometric pattern observed in zebrafish."So how do we ask a fish if it has photoreceptor defects?" he asked.Fadool explained that because the mosaic pattern of zebrafish photoreceptors is so precise, mutations causing subtle alterations are easier to uncover than in retinas with a "messier" arrangement."Just as we can easily recognize a checkerboard mistakenly manufactured with some of the squares changed from black to red or with all-black squares, by using fluorescent labeling and fluorescence microscopes we can see similar changes in the pattern of the zebrafish photoreceptor mosaic," he said. "Karen showed that within the mosaic of the lots-of-rod fish, the position on the checkerboard normally occupied by a UV cone is replaced with a rod. The identity of the mutated gene is then discovered using a combination of classical genetics and genomic resources."Funding for the Fadool laboratory's zebrafish research comes in large part from a five-year grant totaling more than $1.7 million from the National Institutes of Health.Journal reference:Alvarez-Delfin et al. Tbx2b is required for ultraviolet photoreceptor cell specification during zebrafish retinal development. Proceedings of the National Academy of Sciences, 2009; 106 (6): 2023 DOI: 10.1073/pnas.0809439106 Source: Florida State University

Worm-like Marine Animal Providing Fresh Clues About Human Evolution

Research on the genome of a marine creature led by scientists at Scripps Institution of Oceanography at UC San Diego is shedding new light on a key area of the tree of life.

Linda Holland, a research biologist at Scripps Oceanography, and her colleagues from the United States, Europe and Asia, have deciphered and analyzed fundamental elements of the genetic makeup of a small, worm-like marine animal called amphioxus, also known as a lancelet.
Amphioxus is not widely known to the general public, but is gaining interest in scientific circles because of its position as one of the closest living invertebrate relatives of vertebrates. Although amphioxus split from vertebrates more than 520 million years ago, its genome holds tantalizing clues about evolution.
The research led by Holland is published in the July issue of the journal Genome Research. A corresponding research paper is published in the June 19 issue of Nature.
Holland and her colleagues studied the genes of the amphioxus species Branchiostoma floridae through samples obtained in recent years during field work off Tampa, Fla.
Because amphioxus is evolving slowly--its body plan remains similar to that of fossils from the Cambrian time--the animal serves as an intriguing comparison point for tracing how vertebrates have evolved and adapted. This includes new information about how vertebrates have employed old genes for new functions.
"We are finding that today's complicated vertebrate has not invented a lot of new genes to become complicated," said Holland, of the Marine Biology Research Division at Scripps Oceanography. "Amphioxus shows us that vertebrates have taken old genes and recombined them, changed their regulation and perhaps changed the gene function."
Originally discovered in the 1700s, amphioxus appears fish-like with a small tail fin and medial fins, but no paired ones. They spend most of their time burrowed in sand, with their snouts extended for filter feeding.
The human genome has only about 25 percent more genes than the amphioxus genome, according to Holland. During evolution, humans have duplicated genes for different functions. Such duplication has given humans and other vertebrates a much larger "toolkit" for making various structures that are absent in amphioxus, including cells for pigment and collagen type II-based cartilage, for example.
In the new research, Holland and her colleagues describe success in probing the roots of important functions such as immunity. While vertebrates have two types of immune systems--innate, which is a general first line of defense against pathogens, and adaptive, involving antibodies specific for particular pathogens--invertebrates like amphioxus have only innate immune systems. In amphioxus, several of these innate immune genes have been independently duplicated many times over. It may be that with a second line of defense, vertebrates, compared with invertebrates like amphioxus, are less reliant on innate immunity to ward off infection.
The neural crest cells of vertebrates are an excellent example of how "old" genes have acquired new functions. In all vertebrates, neural crest cells migrate from the developing neural tube throughout the body, giving rise to such structures as pigment cells, cartilage of the head and a number of other cell types. Although amphioxus has a brain and spinal cord and makes them using the same genes in the same way as vertebrates, amphioxus has no neural crest cells. Even so, amphioxus has all of the genes necessary for generating migratory neural crest cells; vertebrates have just put them together in new ways. It can be compared with a chef who takes basic leftovers in a refrigerator and whips up a fine gourmet dish.
"The take-home message from this sequencing is that the human and amphioxus genomes are very much alike," said Holland.
A collaborative effort of some 30 laboratories around the world solved the sequence of the amphioxus genome.
Further, deeper analyses between the amphioxus and human genomes in the years ahead will provide even more important clues about genetic evolution.
"All of this is just the tip of the iceberg," said Holland. "It will take a number of years for people to look in greater depth at the amphioxus and human genomes. In terms of figuring out what evolution has done and how it generally works, the amphioxus genome has really been a goldmine and will continue to be one in the years ahead."
In addition to Holland, coauthors of the Genome Research paper include: Ricard Albalat, Kaoru Azumi, Èlia Benito-Gutiérrez, Matthew J. Blow, Marianne Bronner-Fraser, Frederic Brunet, Thomas Butts, Simona Candiani, Pieter J. de Jong, Larry J. Dishaw, David E. K. Ferrier, Jordi Garcia-Fernàndez, Jeremy J. Gibson-Brown, Carmela Gissi, Adam Godzik, Finn Hallböök, Dan Hirose, Kazuyoshi Hosomichi, Tetsuro Ikuta, Hidetoshi Inoko, Masanori Kasahara, Jun Kasamatsu, Takeshi Kawashima, Ayuko Kimura, Masaaki Kobayashi, Zbynek Kozmik, Kaoru Kubokawa, Vincent Laudet, Gary W. Litman, Alice C. McHardy, Daniel Meulemans, Masaru Nonaka, Robert P. Olinski, Kazutoyo Osoegawa, Zeev Pancer, Len A. Pennacchio, Mario Pestarino, Jonathan P. Rast, Isidore Rigoutsos, Marc Robinson-Rechavi, Graeme Roch, Hidetoshi Saiga, Yasunori Sasakura, Masanobu Satake, Yutaka Satou, Michael Schubert, Nancy Sherwood, Takashi Shiina, Naohito Takatori, Javier Tello, Pavel Vopalensky, Shuichi Wada, Anlong Xu, Yuzhen Ye, Keita Yoshida, Fumiko Yoshizaki, Jr-Kai Yu, Qing Zhang, Christian M. Zmasek, Nicholas H. Putnam, Daniel S. Rokhsar, Noriyuki Satoh and Peter W. H. Holland.
Additional participants in the amphioxus genome project included Pieter de Jong and Kazutoyo Osoegawa of Children's Hospital Oakland (CHORI).
The research was funded by grants from the National Science Foundation (USA), National Institutes of Health (USA), the Wellcome Trust (UK), BBSRC (UK), MEXT (Japan), Center for Applied Genomics MSMT and Academy of Sciences (Czech Republic), and the 21th Century and Global COEs at Kyoto University (Japan), Ministerio de Educación y Ciencia (Spain), MIUR (Italy), FIRB 2001 BAU01WAFY, and from MENRT, CNRS and CRESCENDO, a European Union Integrated Project of FP6.
Adapted from materials provided by University of California - San Diego.

Zebrafish Provide Useful Screening Tool For Genes, Drugs That Protect Against Hearing Loss

A small striped fish is helping scientists understand what makes people susceptible to a common form of hearing loss, although, in this case, it's not the fish's ears that are of interest. In a new study researchers at the University of Washington have developed a research method that relies on a zebrafish's lateral line -- the faint line running down each side of a fish that enables it to sense its surroundings -- to quickly screen for genes and chemical compounds that protect against hearing loss from some medications

"The fish's lateral line contains sensory cells that are functionally similar to those found in the inner ear, except these are on the surface of the fish's body, making them more easily accessible," said James F. Battey, Jr., M.D., Ph.D., director of the NIDCD.* "This means that scientists can very efficiently analyze the sensory structures under different conditions to find out what is likely to cause damage to these structures and, conversely, what can protect them from damage."
When people are exposed to some antibiotics and chemotherapy agents, the sensory structures in the inner ear, called hair cells, can be irreversibly damaged, resulting in hearing loss and balance problems. Such medications are called ototoxic. People vary widely in their susceptibility to these agents as well as to damage caused by other chemical agents, loud sounds and aging.
To find out why this is so, senior scientists Edwin Rubel, Ph.D., David Raible, Ph.D. and their research team developed a screening strategy that uses hair cells in the lateral line of zebrafish larvae to signal how hair cells in a person's inner ear might respond under similar conditions. Hair cells are named for small bristly extensions, or stereocilia, jutting from their tops. Movement of fluid (triggered by sound vibrations in the inner ear or changes in water pressure in the fish's environment) causes the stereocilia to tilt to one side, generating an electrical impulse that travels to the brain.
The researchers first set out to identify genes that may be involved in how hair cells respond to ototoxic medicines. Using a chemical that causes random mutations in zebrafish, the researchers bred various fish families, with each family exhibiting a different set of mutations. The researchers then exposed five-day-old larval offspring to the drug neomycin, a type of antibiotic that damages these hair cells as well as those in the human inner ear. The larvae were then stained to determine if the hair cells were still intact. Fish that were resistant to damage were quickly identified as were those that were especially vulnerable.
Using genetic techniques, the group then examined the larvae's DNA, searching for segments that were closely tied to the desired property। In doing so, they zoomed in on five mutations--each located on different genes--that, when inherited from each parent, protected against hair cell damage. Further examination revealed that one of the identified genes corresponds to a gene that is also found in other vertebrates, including humans. Another five mutations were identified that offer protection under more complex genetic conditions.

Next, the team investigated whether they could identify chemical compounds that protect hair cells against ototoxic medicines. Using the same screening technique--exposing five-day-old zebrafish larvae to neomycin and later applying special stains to the hair cells--the researchers screened more than 10,000 compounds and narrowed them down to two similar chemicals that provide robust protection of hair cells against the neomycin. One of the compounds was later found to protect hair cells from a mouse's inner ear against the drug, indicating that the same compound may be protective for other mammals as well.
"One of the pluses about working with zebrafish is that, like other fish, they produce hundreds of offspring. We can look at lots of animals and we can look at many hair cells per animal, which means that we can get good quantitative data," said Dr. Raible.
The authors suggest that their research technique, which combines chemical screening with traditional genetic approaches, offers a fast and efficient way to identify potential drugs and drug targets that may one day provide therapies for people with hearing loss and balance disorders.
Journal reference: Owens KN, Santos F, Roberts B, Linbo T, Coffin AB, et al. (2008) Identification of Genetic and Chemical Modulators of Zebrafish Mechanosensory Hair Cell Death. PLoS Genet 4(2): e1000020. doi:10.1371/journal.pgen.1000020
*The study was funded in part by the National Institute on Deafness and Other Communication Disorders (NIDCD), one of the National Institutes of Health. Other sponsors of the study include the American Academy of Otolaryngology--Head and Neck Surgery Foundation, the University of Washington Royalty Research Fund and the V.M. Bloedel Hearing Research Center.
Adapted from materials provided by NIH/National Institute on Deafness and Other Communication Disorders.

Extracts Of Catfish Caught In Polluted Waters Cause Breast Cancer Cells To Multiply

Exposing estrogen-sensitive breast cancer cells to extracts of channel catfish caught in areas with heavy sewer and industrial waste causes the cells to multiply, according to a University of Pittsburgh study।

The study, which tested extracts from channel catfish caught in the Allegheny and Monongahela rivers near Pittsburgh, suggests that the fish, caught in areas of dense sewer overflows, contain substances that mimic the actions of estrogen, the female hormone. Since fish are sentinels of water quality, as the canary in the coal mine is a sentinel of air pollution, and can concentrate fat soluble chemicals from their habitats within their bodies, these results suggest that pharmaceutical estrogens and xeno-estrogenic chemicals, those that mimic estrogens in the body, may be making their way into the region's waterways.
"We believe there are vast quantities of pharmaceutical and xeno-estrogenic waste in outflows from sewage treatment plants and from sewer overflows, and that these chemicals end up concentrated and magnified in channel catfish from contaminated areas," said Conrad D. Volz, Dr.P.H., M.P.H., principal investigator, department of environmental and occupational health, University of Pittsburgh Graduate School of Public Health. Sewer overflows result from inadequate sewer infrastructure, which releases raw, untreated sewage directly into area rivers during wet weather, according to Dr. Volz. "In Pittsburgh alone, 16 billion gallons of raw, untreated sewage are deposited into area rivers every year with major implications for public health."
In the study, Dr. Volz and colleagues exposed extracts of catfish to estrogen-responsive and estrogen non-responsive human breast cancer cells. They found that catfish extracts caused the estrogen-responsive breast cancer cells to multiply by binding to and activating estrogen receptors -- the proteins within cells that render the cells sensitive to estrogen -- but had no effect on the estrogen negative cell line. Extracts of fish caught in areas heavily polluted by industrial and municipal wastes resulted in the greatest amount of cell growth. This growth occurred regardless of the sex of the fish.
According to Dr। Volz, the next step in this research is to identify the specific estrogenic chemicals and their sources in the local water and fish. "These findings have significant public health implications, since we drink water from the rivers where the fish were caught. Additionally, the consumption of river-caught fish, especially by semi-subsistence anglers, may increase their risks for endocrine-related health issues and developmental problems," said Dr. Volz.

This research was presented at the annual meeting of the American Public Health Association in Washington, D.C. at a special session on "Contaminants in Freshwater Fish: Toxicity, Sources and Risk Communication," on Nov. 7, 2007.
The study was funded by grants from the Highmark Foundation, the DSF Charitable Trust and the Heinz Endowments. Co-authors of the study include Yan Liu, Christopher Price, Mary Elm, Devra Davis, Ph.D., Maryann Donovan, Ph.D., and Patricia Eagon, Ph.D., all with the University of Pittsburgh.
Adapted from materials provided by University of Pittsburgh Schools of the Health Sciences, via EurekAlert!, a service of AAAS.

Skin Color Evolution In Fish And Humans Determined By Same Genetic Machinery

When humans began to migrate out of Africa about 100,000 years ago, their skin color gradually changed to adapt to their new environments. And when the last Ice Age ended about 10,000 years ago, marine ancestors of ocean-dwelling stickleback fish experienced dramatic changes in skin coloring as they colonized newly formed lakes and streams. New research shows that despite the vast evolutionary gulf between humans and the three-spined stickleback fish, the two species have adopted a common genetic strategy to acquire the skin pigmentation that would help each species thrive in their new environments.

The researchers, led by Howard Hughes Medical Institute investigator David Kingsley, published their findings in the December 14, 2007, issue of the journal Cell. Kingsley and first author Craig Miller are at the Stanford University School of Medicine, and other co-authors are from the University of Porto in Portugal, the University of British Columbia, the University of Chicago, and the Pennsylvania State University Further studies of stickleback, they say, may reveal other malleable pieces of genetic machinery both fish and humans have used for adaptation.
The stickleback has become a premier model organism for studying evolution because of its extraordinary evolutionary history, said Kingsley. "Sticklebacks have undergone one of the most recent and dramatic evolutionary radiations on earth," he said. When the last Ice Age ended, giant glaciers melted and created thousands of lakes and streams in North America, Europe, and Asia. These waters were colonized by the stickleback's marine ancestors, which subsequently adapted to life in freshwater. "This created a multitude of little evolutionary experiments, in which these isolated populations of fish adapted to the new food sources, predators, water color, and water temperature that they found in these new environments," Kingsley explained.
Among those adaptations were new colorations that helped the fish camouflage themselves, distinguish species, and attract mates in their new environments. Until now, however, scientists had not understood what genetic factors drove the changes in skin pigmentation.

Human populations have also undergone pigmentation changes as they have adapted to life in new environments. The ecological reasons for those changes may be quite different from the forces driving the evolution of pigmentation in sticklebacks, said Kingsley. As human populations migrated out of Africa into northern climates, the need for darker pigmentation necessary to protect against the intense tropical sun diminished. With skin that was more transparent to sunlight, humans were better able to produce sufficient vitamin D in their new climate.
To begin to understand the genetic basis of skin pigmentation changes in fish, Kingsley and his colleagues crossed stickleback species that had different pigmentation patterns and used genetic markers and the recently completed sequence map of the fish's genome to search for the mechanism regulating stickleback pigmentation. They searched for chromosome segments in the offspring that were always associated with inheritance of dark or light gills and skin. Through detailed mapping of one such segment, Kingsley and his colleagues found that a gene called Kitlg (short for "Kit ligand") was associated with pigmentation inheritance. Kitlg was an excellent candidate for regulating pigmentation because mutant forms of the corresponding gene in mice produce changes in fur color, said Kingsley.
The Kitlg gene is involved in a variety of biological processes, including germ cell development, pigment cell development, and hematopoiesis. Light-colored fish have regulatory mutations that reduce expression of the Kitlg gene in gills and skin, but that do not reduce the gene's function in other tissues. "By altering expression of this gene in one particular place in the body, the fish can fine tune the level of expression of that factor in some tissues but not others," said Kingsley. "That lets evolution produce a big local effect on a trait like color while preserving the other functions of the gene."
Humans also have a Kitlg gene, and Kingsley and his colleagues wondered if it played a role in regulating the pigmentation of human skin. One clue they had came from previous research by other groups that had revealed that the human Kitlg gene has undergone different changes among different human populations, suggesting that it is evolutionarily significant.
Kingsley and his colleagues tested whether the different human versions of the Kitlg gene are associated with changes in skin color. Humans with two copies of the African form of the Kitlg gene had darker skin color than people with one or two copies of the new Kitlg variant that is common in Europe and Asia.
Knowing that people had also adapted lighter skin when they migrated north, Kingsley wondered whether mutations in the same gene accounted for light pigmentation in people living in northern climes. In the north, where less sunlight reaches the ground, lighter coloring helps people absorb enough sunlight to produce vitamin D.Kingsley and his colleagues collected DNA from people with a variety of skin colors to look for alterations in the Kit ligand gene. Sure enough, people with lighter skin had an altered form of the gene. He said this gene isn’t alone in controlling a person’s skin color, but it does seem to account for about 20 percent of the differences in pigmentation between people of African and northern European descent.“It is the same genetic mechanism between organisms that are very different from each other,” Kingsley said. This gene is known to make a protein that plays a role in maintaining the melanocyte skin cells that control pigmentation.In terms of how evolution progresses, this gene would be a large ladle of dye that helps set the paint color apart from the original. Additional genetic changes account for the exact color of each person’s skin.
"Although multiple chromosomal regions contribute to the complex trait of pigmentation in both fish and humans, we have identified one gene that plays a central role in color changes in both species," said Kingsley.
"Since fish and humans look so different, people are often surprised that common mechanisms may extend across both organisms," he said. "But there are real parallels between the evolutionary history of sticklebacks and humans. Sticklebacks migrated out of the ocean into new environments about ten thousand years ago. And they breed about once every one or two years, giving them five thousand to ten thousand generations to adapt to new environments."
Although modern humans arose in Africa, they are thought to have migrated out of Africa in the last 100,000 years. "Humans breed about once every 20 years, giving them about 5,000 generations or so to emerge from an ancestral environment and colonize and adapt to new environments around the world," Kingsley added. "So despite the difference in total years, the underlying process is actually quite similar. Whether it be fish or humans, there were small migrating populations encountering new environments and evolving significant changes in some traits in a relatively short time. And the genetic mechanisms that can produce these changes may be so constrained that evolution will tend to use the same sorts of genes in different organisms."
Kingsley and his colleagues are now exploring the genetic basis of other evolved traits in the stickleback that could find a parallel in humans. "And given the degree to which evolutionary mechanisms appear to be shared between populations and organisms, we're optimistic about finding the particular genes that underlie other recent adaptations to changing environments in both fish and humans," he said.
Adapted from materials provided by Howard Hughes Medical Institute.

Conquest of land orgin in Shark genome

Scientists at the University of Florida have identified genetic activity in sharks required for the development of hands, feet, fingers and toes in limbed animals। The finding shows what was thought to be a relatively recent evolutionary innovation existed eons earlier than previously believed, potentially providing insight for scientists seeking ways to cure human birth defects.

When the first four-legged animals sprouted fingers and toes, they took an ancient genetic recipe and simply extended the cooking time, say University of Florida scientists writing in Wednesday's issue of the journal PLoS One.
Even sharks -- which have existed for more than half a billion years -- have the recipe for fingers in their genetic cookbook -- not to eat them, but to grow them.
While studying the mechanisms of development in shark embryos, UF scientists identified a spurt of genetic activity that is required for digit development in limbed animals.
Previous work suggested that the transition from fins to limbs involved the addition of a late phase of gene activity during embryonic development, something thought to be absent during the development of fish fins.
The finding shows what was thought to be a relatively recent evolutionary innovation existed eons earlier than previously believed, shedding light on how life on Earth developed and potentially providing insight for scientists seeking ways to cure human birth defects, which affect about 150,000 infants annually in the United States.
"We've uncovered a surprising degree of genetic complexity in place at an early point in the evolution of appendages," said developmental biologist Martin Cohn, Ph।D., an associate professor with the UF departments of zoology and anatomy and cell biology and a member of the UF Genetics Institute. "Genetic processes were not simple in early aquatic vertebrates only to become more complex as the animals adapted to terrestrial living. They were complex from the outset. Some major evolutionary innovations, like digits at the end of limbs, may have been achieved by prolonging the activity of a genetic program that existed in a common ancestor of sharks and bony fishes."

Researchers say the same genes that produced ancient fins likely enlarged their role about 365 million years ago in amphibians struggling to adapt to swamps and terrestrial living, creating a distinct burst of development and more versatile appendages.
Using molecular markers to study the formation of skeletal cartilage in embryos of the spotted catshark, UF scientists isolated and tracked the activity of Hox genes, a group of genes that control how and where body parts develop in all animals, including people.
They discovered a phase of gene expression in sharks that was thought until recently to occur only when digits began to form in limbed animals.
Why, then, don't sharks have fingers?
Renata Freitas and GuangJun Zhang, co-authors of the paper and graduate students in the zoology department of the College of Liberal Arts and Sciences, speculate that sharks and many other types of fish do not form more dramatic appendages during this late phase of Hox gene expression because it occurs briefly and only in a narrow band of cells, compared with the more extended time frame and larger anatomical area needed to prefigure the hand and foot in limbed animals.
"We know when this particular Hox gene is mutated in humans, it results in malformations of fingers and toes," Cohn said. "Until now it was thought these mutations were affecting a relatively recent innovation in the genetic process of limb development. Our results show that this phase of Hox expression is much more ancient and suggest that if the origin of digits involved a prolonged activity of Hox genes, a truncated period could result in defective digits."
In a parallel study, researchers at the University of Chicago found this second phase of gene expression in paddlefish, a primitive living descendant of early fish with the first bony skeletons.
Finding the second phase in sharks, which have skeletons consisting not of bone but of cartilage, means the genetic processes necessary to muster fingers and toes existed more than 500 million years ago in the common ancestor of fish with cartilaginous skeletons and bony fish -- more than 135 million years before digits debuted in the earliest limbed animals.
"The leap from aquatic life to terrestrial life is an extremely dramatic, important point in evolution that has captured the interest of many," said Marie Kmita, Ph.D., director of the Genetics and Development Research Unit at the Institut de Recherches Cliniques de Montréal who was not involved in the research. "Understanding how changes in gene regulation modify the body architecture is of extreme interest to scientists who are trying to find ways to improve human health by learning from developmental processes. This work shows a late phase of gene regulation seems fated to the emergence of digits."
Note: This story has been adapted from a news release issued by University of Florida.

Modern Brains Have An Ancient Core

Hormones control growth, metabolism, reproduction and many other important biological processes. In humans, and all other vertebrates, the chemical signals are produced by specialised brain centres such as the hypothalamus and secreted into the blood stream that distributes them around the body.

Researchers from the European Molecular Biology Laboratory [EMBL] now reveal that the hypothalamus and its hormones are not purely vertebrate inventions, but have their evolutionary roots in marine, worm-like ancestors. In this week's issue of the journal Cell they report that hormone-secreting brain centres are much older than expected and likely evolved from multifunctional cells of the last common ancestor of vertebrates, flies and worms.
Hormones mostly have slow, long-lasting and body-wide effects, rendering them the perfect complement to the fast and precise nervous system of vertebrates. Also insects and nematode worms rely on the secretion of hormones to transmit information, but the compounds they use are often very different from the vertebrate counterparts.
"This suggested that hormone-secreting brain centres have arisen after the evolution of vertebrates and invertebrates had split," says Detlev Arendt, whose group studies development and evolution of the brain at EMBL. "But then vertebrate-type hormones were found in annelid worms and molluscs, indicating that these centres might be much older than expected."
Scientist Kristin Tessmar-Raible from Arendt's lab directly compared two types of hormone-secreting nerve cells of zebrafish, a vertebrate, and the annelid worm Platynereis dumerilii, and found some stunning similarities. Not only were both cell types located at the same positions in the developing brains of the two species, but they also looked similar and shared the same molecular makeup. One of these cell types secretes vasotocin, a hormone controlling reproduction and water balance of the body, the other secretes a hormone called RF-amide.
Each cell type has a unique molecular fingerprint - a combination of regulatory genes that are active in a cell and give it its identity. The similarities between the fingerprints of vasotocin and RF-amide-secreting cells in zebrafish and Platynereis are so big that they are difficult to explain by coincidence. Instead they indicate a common evolutionary origin of the cells. "It is likely that they existed already in Urbilateria, the last common ancestors of vertebrates, insects and worms" explains Arendt.
Both of the cell types studied in Platynereis and fish are multifunctional: they secrete hormones and at the same time have sensory properties. The vasotocin-secreting cells contain a light-sensitive pigment, while RF-amide appears to be secreted in response to certain chemicals. The EMBL scientists now assume that such multifunctional sensory neurons are among the most ancient neuron types. Their role was likely to directly convey sensory cues from the ancient marine environment to changes in the animal's body. Over time these autonomous cells might have clustered together and specialised forming complex brain centres like the vertebrate hypothalamus.
"These findings revolutionise the way we see the brain," says Tessmar-Raible. "So far we have always understood it as a processing unit, a bit like a computer that integrates and interprets incoming sensory information. Now we know that the brain is itself a sensory organ and has been so since very ancient times."
Article: Tessmar-Raible, K., Raible,F., Christodoulou, F., Guy, K., Rembold, M., Hausen, H. and Arendt, D. Evolution of the vertebrate hypothalamus: An ancient set of sensory–neurosecretory cell types in the annelid and vertebrate brain, Cell, 29 June 2007
Note: This story has been adapted from a news release issued by European Molecular Biology Laboratory.

Sea urchins genome is remarkably similar to Human

Sea urchins are small and spiny, they have no eyes and they eat kelp and algae. Still, the sea creature's genome is remarkably similar to humans' and may hold the key to preventing and curing several human diseases, according to a University of Central Florida researcher and several colleagues.UCF Professor Cristina Calestani was part of the Sea Urchin Genome Sequencing Group, which recently completed sequencing of the sea urchin genome and published its findings in the November issue of Science. The National Institutes of Health funded most of the nine-month project.The genome of the purple sea urchin is composed by 814 "letters" coding for 23,300 genes.Sea urchins are echinoderms, marine animals that originated more than 540 million years ago. The reason for the great interest in sequencing the sea urchin genome is because it shares a common ancestor with humans. Sea urchins are closer to human and vertebrates from an evolutionary perspective than other more widely studied animal models, such as fruit fly or worms. The purple sea urchin, in fact, has 7,000 genes in common with humans, including genes associated with Parkinson's, Alzheimer's and Huntington's diseases and muscular dystrophy."Another surprise is that this spiny creature with no eyes, nose or hears has genes involved in vision, hearing and smell in humans," Calestani said. "The comparison of human genes with their corresponding ancestral sea urchin genes may give important insight on their function in humans, in the same way the study of history helps understanding the reality of our modern world." The genome sequencing project was led by Erica Sodergren and George Weinstock at the Baylor College of Medicine-Human Genome Sequencing Center in Houston, along with Dr. Richard Gibbs, director of the Baylor center, and Drs. Eric Davidson and Andrew Cameron at the California Institute of Technology.Of particular interest to Calestani is the way the sea urchin's immune system works. The human immune system has two components: innate immunity, with which we are born, and acquired immunity, which is the ability to produce antibodies in response to an infection. Sea urchins only have innate immunity, and it is greatly expanded with 10 to 20 times as many genes as in human."Considering that sea urchins have a long life span -- some can live up to 100 years -- their immune system must be powerful," Calestani said. "Sea urchins could very well provide a new set of antibiotic and antiviral compounds to fight various infectious diseases."The sea urchin has been used for many years as a research model to study embryonic development.Cell development is very complicated. In order to properly regulate just one gene expression of a single-cell layered gut of the sea urchin larva, at least 14 proteins binding the DNA at 50 sites are needed, Calestani said."Multiply that hundreds of times and you begin to understand the level of complexity involved in human development," she added.Using a "simple" creature like the sea urchin embryo to uncover the molecular basis underlying development offers several experimental advantages compared to the use of mice. Raising sea urchin embryos is easy and inexpensive. One female can provide up to 20 millions eggs. The embryos develop in just three days and are transparent. Also, single cells can be easily observed live in the embryos. "If we know how these biological processes work, then we can begin to figure out how to intercede to repair and to heal," Calestani said. "It holds a lot of promise."Calestani is continuing her work with sea urchins at UCF in Orlando by examining the development of pigment cells found in the marine creatures. Those cells also might provide some insight into human immunity to diseases.Calestani, who teaches genetics at UCF, worked with Davidson at Caltech before arriving at UCF.