Why is the frog genome so much larger than a fish's?

Why is the frog genome so much larger than a fish's?

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As we have heard in the summaries of the human ENCODE project, 80 per cent of junk DNA appears to have an essential function. Many fish have a genome with only one tenth the size of a usual vertebrate genome. Why can fish have 1/10th of junk DNA and be still fully functional? What has a frog more than a fish has? I'm especially interested if we can see the difference somewhere, complexity of physiology or anatomy, or such.

Jap. puffer fish genome: 390 Megabases, 47,800-49,000 genes (UniProt)

Medaka genome: 690 Megabases, 24,600 genes

Clawed frog: 1,500 Megabases, 23,500 genes

Genome size is a poor indicator of an organism's complexity (already an ill-defined term). We cannot assume by any means that a larger genome corresponds to a more "complex" organism. There are some plants whose genomes are larger than most mammals, and indeed the largest eukaryotic genome (at least as of 2010) is the plant Paris japonica, weighing in at 1C = 152.23 pg (compared to Homo sapiens at 1C = 3 pg). Anecdotally, in my previous research lab I discussed with a colleague a fungal species whose genome size differed by orders of magnitude between different individuals of that species.

It should never surprise you to see an organism with a larger genome size than what you may consider to be a more complex organism.

See here for an ENCODE author's reflections on their use of the word "functional". (I don't think anyone is using the word "essential".)

It is clear from this that, for them, one class of functional DNA is intronic DNA: i.e. introns are defined by ENCODE as functional DNA. It is well known that puffer fish have reduced genomes and that this is largely due to the presence of much smaller introns, although the number and positioning of these introns is broadly similar to what is seen in other vertebrates. One classic example of this is the huntingtin gene which is 7.5 times shorter in pufferfish than in humans even though both genes have 67 introns. In fact the average fish genome size is 5-6 times bigger than that for pufferfish (zebrafish is around this average value).

Although ENCODE are defining intronic DNA as functional I don't think that they are claiming a specific function for each and every intron, let alone each base in those introns. So there is still a lot of scope for the observed differences in genome size.

By separating life stages, metamorphosis may circumvent harmful evolutionary tradeoffs

Wood frogs must adapt to two very different habitats: ephemeral pools for tadpoles, and the forest floor for frogs. Metamorphosis might compartmentalize genetically correlated traits so that natural selection acts more efficiently. Image Credit: Debora Goedert

There’s no guarantee evolution will bestow the best version of every trait. The benefits of one trait may impose a cost when an unfavorable trait, correlated genetically, comes along for the ride. In a recent study on wood frogs (Rana sylvatica) published in The American Naturalist, researchers found evidence suggesting that metamorphosis might reduce such cases of genomic conflict.

The findings may explain why metamorphosis, a risky and physiologically expensive process, persists in nature. “It’s adaptive,” says paper coauthor and evolutionary biologist Debora Goedert, a graduate student at Dartmouth College in Hanover, NH, and a fellow of Brazil’s Science Without Borders program. “And the reason why it’s adaptive is because it allows organisms to separate these two life stages in such a way where they can be optimum in both life stages and not carry some sort of specialization tradeoff where becoming a really good tadpole now means you are a terrible frog, or vice versa.”

The wood frog must adapt to two wildly different habitats: ephemeral pools for its tadpole stage, and the forest floor for its frog stage. Preliminary research had suggested that metamorphosis might effectively compartmentalize genetically correlated traits, allowing natural selection to act only on the trait that’s needed during a particular life stage—such as tails in tadpoles—rather than simultaneously enhancing a positive trait and an unrelated but genetically correlated disadvantageous trait.

The recent study combines quantitative genetic evidence with estimates of natural selection, bolstering the hypothesis that metamorphosis may be adaptive. Breeding studies in the lab enabled a look at genetic correlations between traits, such as tadpole tail length, frog leg length, and head size in both life stages. To examine how natural selection acted on these traits, the researchers built simulated ponds in the forest. There, they measured predation on tadpoles by beetle larvae with giant mandibles, on juvenile frogs by garter snakes, and on adult frogs by kestrels and small mammals.

The researchers not only identified genetically correlated traits undergoing conflicting selection within and between the wood frog’s two life stages, but also determined that metamorphosis alters the degree of correlation of the traits throughout the frog’s lifespan. They found that the degree of genomic conflict was lower between life stages than within for both the tadpole and frog, suggesting that metamorphosis lowers the conflict between antagonistic traits.

“A strength of this article is that they’re trying to cast genomic conflict in terms of descriptions at the trait level,” says Stevan J. Arnold, an evolutionary biologist and professor emeritus at Oregon State University in Corvallis who was not involved in the research. “I think this is a big triumph, to have done a study that quantifies both the nature of selection and the nature of genetic correlation between traits.” The work “helps us understand how and why metamorphosis evolves,” Arnold adds.

Whether or not these observations represent “genomic conflict,” however, is a matter of some debate. Traditionally, researchers have defined it in terms of evolutionary conflict between identifiable genes. But so little is known about the frog genome relative to other organisms that the researchers had to broaden the definition to include traits that are likely controlled by multiple genes. Nonetheless, they say, the breeding studies point to correlated genetic elements underlying the traits—they’re just not able to identify them yet. “It’s an early stab at establishing genomic conflict,” says Goedert. She and her advisor, coauthor Ryan Calsbeek, also an evolutionary biologist at Dartmouth, acknowledge that they have not yet established a definitive causal link between metamorphosis and the decoupling of traits embroiled in genomic conflict.

The field is trying now to “figure out how to grapple with testing both this idea of antagonistic selection and its consequences,” Arnold says. “For a full testing of the theory there’s a need for a more detailed enunciation of the underlying model. What’s the bigger picture? That’s an agenda probably for the next ten years.”

Why is the frog genome so much larger than a fish's? - Biology

Xenopus are an invaluable tool to study vertebrate embryology and development, basic cell and molecular biology, genomics, neurobiology and toxicology and to model human diseases.

Studying model organisms, such as Xenopus, allows us to decipher how regulatory and interactions networks direct embryonic development, how they adapt during aging and under environmental stress, and how they become dysregulated to cause disease, malformations and birth defects.

Several features make Xenopus eggs and embryos an outstanding tool in biomedical research.

  • embryos tolerate extensive manipulation (e.g. single cell , germ layer dissections, tissue transplantations
  • easy to inject of a range of materials (e.g. nucleic acids, proteins, whole nuclei) into whole embryo or specific cells
  • cell fate of each early embryonic cell is known, allowing targeted gene knock-out, knockdown and overexpression studies
  • eggs and embryos provide abundant source for high-throughput biochemical studies
  • cell-free extracts made from Xenopus oocytes are a premier in vitro system for studies of fundamental aspects of cell and molecular biology
  • Xenopus oocytes are a leading system for studies of ion transport and channel physiology
  • Xenopus oocytes widely used assay environmental toxicology
  • large-scale genetic screens has identified genes involved in diverse developmental and physiological processes

Background of Xenopus

Xenopus is a genus of African frogs that are commonly known as the African clawed frogs. Two species of Xenopus are regularly used by biologists, Xenopus laevis and Xenopus tropicalis. Both species are fully aquatic, and are easy to maintain in captivity. Frog eggs are large (

1.2mm diameter), produced in large quantities, and easy to manipulate. This makes them a valuable tool to investigate the early period of embryonic development. Egg production can be stimulated by injection of chorionic gonadotropin. In the 1930's, doctors used Xenopus as a simple pregnancy test for women- because this hormone is present in the urine of a pregnant woman, the frog would be induced to lay eggs. Biologists utilize this same method to induce the production of eggs on demand in the laboratory. The frogs are then rested for a few months, when they can be induced again. Very few species of frog can be induced to produce eggs in such a controlled manner, and this is another reason why Xenopus is so popular with developmental and cell biologists.

Frog embryos develop externally, allowing experiments to be performed prior to, or directly following fertilization. Rapid embryo growth and development means that within a couple of days, a tadpole has a fully functional set of organs, and it can be examined to determine if any experimental intervention has had an effect.

Comparing the two species, X.tropicalis has a much shorter life cycle than does X. laevis, growing to adult in 4 months compared with 12 months, making it a faster system to study. X. tropicalis is also diploid (i.e., it has two sets of chromosomes), while X. laevis is allotetraploid (a form of tetraploid, i.e. it has four sets of chromosomes), thus X.tropicalis is a more simple model for genetic studies.

The genomes of both X. laevis and X. tropicalis have been sequenced. They display remarkable structural similarity with the human genome (Hellsten et al. ,2010) meaning that findings from Xenopus provide insights into many human conditions and diseases.

Advantages of Xenopus as a Model Organism

Category: C. elegans Drosophila Zebrafish Xenopus Chicken Mouse
Cost per embryolowlowlowlowmediumhigh
High-throughput multiwell-format screeninggoodgoodgoodgoodpoorpoor
Access to embryosgoodgoodgoodgoodpoorpoor
Micro-manipulation of embryoslimitedlimitedfairgoodgoodpoor
Knockdowns (RNAi, morpholinos)goodgoodgoodgoodlimitedlimited
Evolutionary distance to humanvery distantvery distantdistantintermediateintermediateclose

Experimental organisms such as frogs (X. laevis and X. tropicalis), nematode worms (C. elegans), fruit flies (Drosphilia spp.), zebrafish (Danio rerio) , chicken (Gallus Gallus) and mice (Mus musculus) are used to discover the molecular mechanisms fundamental to life, thereby providing a shortcut to understanding human biology. Each model organism has it's advantages and disadvantages, and these are compared in the table to the right (adapted from Wheeler and Brändli 2009).

Phylogenetic tree showing the main animal models commonly used in biomedical research and their evolutionary relationships. The divergence time, in millions of years (Mya), is based on multiple gene divergence and protein divergence studies.
Adapted from Wheeler & Brändli 2009 Dev Dyn 238:1287-1308.

As a group, amphibians are phylogenetically well positioned for comparisons to other vertebrates, having diverged from the amniote lineage (mammals, birds, reptiles) some 360 million years ago. The comparison with mammalian and bird genomes also provides an opportunity to examine the dynamics of tetrapod chromosomal evolution. The genomes of both X. laevis and X. tropicalis species have been sequenced and display remarkable structural similarity with the human genome, meaning that findings from Xenopus provide insights into many human conditions and diseases.

So in summary, Xenopus is a valuable tool because they are:

  • hardy, fully aquatic and easy to maintain in the laboratory
  • produce eggs year-round
  • eggs are a reliable and flexible material for research
  • embryos are a good model for vertebrate development
  • genetically similar to humans thus a good model for human disease

Read more about
Biological Discoveries and Biomedical Research using Xenopus (coming soon).

Rule Breaker To Buy PE Celera Genomics Corp.

** This trade is being made under the regular portfolio policy, namely, once The Fool announces an intention to trade, that trade will be made within the next five trading days. For more detail, please read the New Trades section of the Rule Breaker Portfolio. **

At some point in the next five market days, the Rule Breaker Portfolio is BUYING approximately $50,000 (about 5.7% of the RB portfolio's current value) of:

PE Celera Genomics Corp. (NYSE: CRA)
761 Main Avenue
Norwalk, CT 06859
Phone: (203) 762-1000
Fax: (203) 762-6000

Closing Price (12/16/99): $76 3/16
Average daily volume: 276,000 shares
Daily dollar volume: $19.87 million

Market Cap: $1.86 billion
12 Month Sales: $10 million
Price-to-Sales ratio: 186

Transaction Stats: On December 17, 1999, the RB Port bought 1,260 shares of Celera at a split-adjusted $39.75 per share, plus an $8 trade commission.

One year ago, we added to the Rule Breaker Portfolio the first of what will be many different investments in companies that use biotechnology. We said at the time that we believed the two most significant Rule-Breaking industries over the foreseeable future are the Internet and biotechnology. And we called that investment, Amgen (Nasdaq: AMGN), a "biotech company," the top dog and first-mover in the "biotech industry."

But truth be told, we now regret that phrasing, because biotechnology is not an industry. It is a technology. There is no "biotechnology industry," per se -- just as there is no "Internet industry." There are many, many companies that use biotechnology or the Internet in order to profit, providing products or services that customers find attractive and valuable. But just try to identify a single "top dog" Internet or biotechnology company. It's not really possible. Again, these are technologies that different companies adopt in order to gain a lead in one industry or another.

We are Rule Breaker investors, and we love biotechnology. We are amazed by our species' increasing ability to understand, and in some critical and exciting ways, reengineer the world in which we live. It puts us in mind again of one of our ten favorite quotes from the Bard, holding as it does so much optimism -- and so much applicability in our own age, a Renaissance of a new sort, but every bit as exciting as what happened in Europe 400 years ago:

What a piece of work is a man! how noble in reason!
how infinite in faculty! in form and moving how
express and admirable! in action how like an angel!
in apprehension how like a god! the beauty of the
world! the paragon of animals!

This classic humanistic expression reminds us not only that we are a piece of work, but that as pieces of work we can actually be reworked. Ask the sufferers of cystic fibrosis who should, not before too long, have a treatment that replaces the single faulty gene responsible for the condition with a healthy gene. Bang-o. That's just one small example of what can be accomplished through genetic engineering. Anyway, before we set down to explaining what we have chosen to dub the next of our Rule Breakers, we must define a few terms.

What does "biotechnology" mean? Good question. Here's what it means to us: Biotechnology is the application of biology for human ends. This is a broad-brush, encompassing definition obtained from the excellent primer Improving Nature?: The Science and Ethics of Genetic Engineering by Michael Reiss and Roger Straughan. It speaks of the use of our understanding of genetics to rework the world in diverse ways that are deemed more satisfying to us, as stewards. The various examples of biotechnology run the gamut from the crossbreeding of plant and animal species by farmers to obtain living beings that otherwise would not have existed (blue roses and bulldogs, for example) to the stimulation of white-blood-cell growth in chemotherapy patients (Neupogen, Amgen's billion-dollar bioengineered protein).

Looked at in this simple, rational conception, biotechnology is not something cooked up in a test-tube by a mad scientist eager to create a man-eating frog the size of an elephant. (OK, we should watch our backs, because something like this may eventually be possible, of course.) No, biotechnology is just a very powerful technology that -- like any other -- must be used responsibly and constructively to beneficial ends.

All sorts of fascinating discussion and debate surrounds all of these ideas, phrases, and words, which it is not within the purview of this report to address. We do look forward in our daily Rule-Breaker scribblings to discussing many thoughts and considerations of the issues at stake here, however. For now, suffice it to say that we consider biotechnology (as we have defined it) "the application of biology for human ends," and, that together with the Internet and the emerging technology of wireless, biotech makes up one of the three most interesting, world-shaping, outrageous, Rule-Breaking technologies of our time. Period.

Which brings us to that other term we wanted to define: "Celera."

What does "Celera" mean, Latin students? Well, our schooling did not include Latin, but our dictionaries retain their etymologies. Inquire about "celerity" of Mr. Webster and you will find the Latin root "celera." Two thousand years ago, that very word -- "celera" -- came off the tongues of Roman philosophers, centurions, and emperors and it meant SPEED. And that is exactly the idea of the word today, in reference to the company we'll be buying. Celera is all about SPEED, about using computers to SPEED up our human understanding of our own genetic code, to SPEED our way toward new genetic destinies, and for this company to SPEED its way past the competing Human Genome Project.

Those who are buying Celera, are buying SPEED.

Let's talk about that. Let's understand it. To do so, we adopt the framework that we use for all Rule Breaker reports. We examine Celera in light of the six Rule-Breaking attributes spelled out in our book, Rule Breakers, Rule Makers. To summarize:

Top dog and first-mover in an important, emerging industry.

Sustainable advantage, gained through business momentum, patents, visionary leadership, or incompetent competitors.

Smart management and good backing.

Excellent past price appreciation, measured by a relative strength of 90 or greater.

The greater the consumer brand, the better.

A recent constituent of the financial media has recently called the company "grossly overvalued."

T op dog and first-mover in an important, emerging industry.

The important, emerging industry in question is human genetic information.

We are presently living in the B.U.G. era, which is one way to view the calendar of human history. B.U.G. years are the years "Before Understanding Genetics" -- human genetics, that is -- which has been one consistent historical era since our planet was formed 4.5 billion years ago. The entire history of Planet Earth has been purely "buggy."

But two key developments have propelled us to the climax of the B.U.G. era. The first is Gregor Mendel's discovery of genetics, which began in the 1850s in Moravia as he crossed varieties of the garden pea in his small monastery garden. The eventual results of this first key development are evident today, where after many further advances and efforts, we are now able to manufacture human proteins and clone animals. The second development is the huge gains in computing power achieved over the past 30 years. It is symbolized perhaps by the laptops upon which this report was created. A little Pentium laptop holds many times the computing power of machines that just one generation ago looked like huge vacuum cleaners and occupied whole rooms. (And you ain't seen nothin' yet -- referring to advances in computing power, that is, not this report.)

Either of these developments on its own provides outstanding rewards in efficiency, productivity, understanding, and the profits netted by those who dreamed them up. But put both of them together -- genetic studies with computing power -- and you arrive at the inevitable result: a total understanding of the genetic map. The same four nitrogenous bases that run through human DNA -- adenine, cytosine, guanine, and thymine -- run through plants, animals, and all living things. We are working toward a total genetic map -- a total understanding of where every gene sits in every creature, and what each one means.

While we are still a long way away from a total genetic map of everything, we are getting increasingly close to a genetic map of one particular species that has always held our imagination and interest: our own. We presently appear to be less than two years away from having mapped human DNA, the human "genome." ("Genome" simply means the total genetic material of a species.)

The plan initially was that this would be a government-sponsored project, called the Human Genome Project, which is a fascinating and worthy effort on the part of many scientists and the government to map the genome. However, recently senior executives at scientific-instrument company, PE Corporation, realized that with enough computational power and the right people onboard, they could complete a full map of the human genome before the federally funded Human Genome Project's year 2005 goal. When PE Corp embarked on its new project, it had one man in mind to lead it. That man (more on him later) had developed a super-fast gene sequencing technique, called a "shotgun technique." PE Corp wanted the inventor of the shotgun technique to lead its new company. The inventor is Craig Venter. The new company is Celera.

So, to cut to the chase on this, the first attribute of the Rule Breaker: Celera is the top dog and first-mover of the important, emerging industry of bioinformatics.

(Required reading: Run your mouse -- don't walk it -- to this message board post, post #4885 from the Rule Breaker Strategies board.)

Celera's business involves decoding genomes, patenting its discoveries, and selling access to its databases, mainly to pharmaceutical and biotechnology companies that want to create cures using genetic engineering. Specifically, the company sells subscriptions to its genome information, will increasingly offer genomic information management and analysis software, and collects royalties and licensing fees resulting from its work.

At its root, then, you can see that Celera is at least as much of an information technology company as it is a biotech company. The information that Celera is on track to discover could be the cornerstone for most future drug research and development. The opportunity to identify and replace one or more genes to cure a disease (not just for the afflicted but for all his or her future offspring) should in most cases be far more effective than hoping to discover a cure or balm from chemicals or organic substances drawn from nature. Realizing this, Celera's mission is to become the definitive source of genomic and related medical and agricultural information.

Will drug companies partner with Celera and pay money to use its information? Amgen, Novartis, Pharmacia & Upjohn, Rhone-Poulenc Rorer, RhoBio and Pfizer have already signed agreements with Celera, agreements totaling more than $100 million in value. And this makes sense, doesn't it? Think about it in the terms used by Tom Headrick, from our Fool community. Tom asks: "How much does it cost to bring a drug to market using today's current methods? How much of that cost will be eroded by having this genetic/biological material available in the database as a springboard launching a new drug or therapy for drug companies?" He closes by pointing out, "That's why they are [working with Celera]."

In the "informatic" part of "bioinformatics," Celera has used the help of its parent company, formerly Perkin-Elmer, now called PE Corporation, to obtain a leadership position. PE Corp supplied Celera with the vital technology and the initial funding needed to generate results. Now, success is already arriving. In record time, Celera completed the sequencing phase of the fruit fly this year, thereby showing its sequencing technology to be the quickest in history. Check this out and see if it makes your spine tingle. From Celera, on September 9, 1999:

"Celera Genomics announced today that it has finished the sequencing phase in deciphering the genome of Drosophila melanogaster, the fruit fly. Over 1.8 billion base pairs -- letters of genetic code -- were sequenced in completing the sequencing phase. Celera began to sequence the genome of Drosophila and deliver data to its subscribers in May 1999. By comparison, the first genome of a free living organism, Haemophilus influenzae, consisting of 2 million letters of genetic code took one year to complete, and other early genomes not using Celera's whole genome shotgun strategy took over a decade to complete.

"Celera now turns all its sequencing resources towards the sequencing phase of the human genome."

Like a battleship swinging its giant guns around to point squarely at you, Celera kicked the fruit fly's sequencing information out with mind-blowing speed and then immediately turned all of its sequencing resources (and you're going to see that's a HECK of a lot of resources) to the human genome.

The following sections of this report will demonstrate, piece by piece, that Celera is the top dog in this important, emerging industry. We'll see how Celera has three times more computational power than its nearest competitor, and how it has 15 times the data management capacity. Celera also employs world-leading scientists and technologists who are capable of handling the SPEED of its computers, and the output. (We want to point out that even if the company fails in business, it will have accelerated the work of others and presumably helped our species a great deal. So, whatever happens, we'll get that satisfaction from this investment.) Celera is so speedy that, although it took over 10 years for other companies to map less than 10% of the human genome, this year Celera has reportedly mapped nearly one-third of it already. It is top dog.

Is the company the "first-mover"?

Celera wasn't the first to consider mapping parts of the human genetic makeup. Incyte Pharmaceuticals (Nasdaq: INCY), Human Genome Sciences, and Gene Logic (Nasdaq: GLGC) moved in this direction before Celera existed, much like dozens of book sellers existed online before (Nasdaq: AMZN). However, Celera is the first mover in attempting to create a highly detailed map of the human genome (all of it), and it is the first to use Venter's shotgun approach and 300 gene sequencers (more on that later) to do the job. It appears that the shotgun approach is working, and working quickly, so being the first mover to use this approach may be what matters most. Using this approach, Celera already leads the human genome "race."

And this race is not crowded. Celera's "competitors," except one, focus on mapping parts of the human genome, not the entire enchilada. The government's Human Genome Project is the only big competitor aiming to complete a map of the human genome, but because it has been using a traditional physical mapping technique (more on that later) it has moved slowly compared to Celera. Also, its ambitions were lower until Celera announced its intentions. As soon as Celera was born, HGSI increased its intentions regarding its mapping of the genome.

So, in the ways that count most, Celera is first mover. As Fool Kevin DeWalt pointed out in his post (CRA board #76), Dr. Venter and Celera have:

  1. Sequenced the first entire genome of a living organism (in 1995).
  2. Most aggressively pursued building the technological platform to sequence DNA.
  3. Committed to becoming the first private [meaning non-government, because it's obviously public] organization to sequence the human genome.

The whole of this report will show how Celera is leading, but where is it going? Once the company owns scads of genome information, what will it do with it?

Celera wants to be the leading provider of genome information and offer multiple services related to the information. Can Celera profitably be a genome information provider? The company's growing list of clients and partners has some people predicting that Celera could be profitable in 2002 or 2003. This prediction is a Crap shoot, but it is not nearly as random as Craps, nor is it beyond logic's reach.

S ustainable advantage, gained through business momentum, patents, visionary leadership, or incompetent competitors.

The best Rule Breakers possess key advantages: Amazon's giant customer base, AOL's worldwide brand name, Starbucks' omnipresence.

Celera has a monstrous technological advantage over all competitors it also is one of the most respected bodies of management in the scientific world and it has shown the greatest speed in mapping a genome. The company's only head-on competition is the Human Genome Project, but at the rate Celera is moving, it could reach its goal by 2001, well before the competition. By computational power, Celera is three times larger than any other gene-sequencing lab in the world, and Celera is on course to house the second-most powerful computational facility on the planet. Celera should be able to sequence 30 billion base pairs of DNA annually, and it will have 10 to 20 times more capacity for sequence information than its largest competitor.

Several companies have undertaken genomic research and isolated gene sequences from the human genome. These companies, including Millennium Pharmaceuticals (Nasdaq: MLNM), Myriad Genetics (Nasdaq: MYGN), Genset (Nasdaq: GENXY), and others, are commercializing their findings, meaning they're selling them to biopharmaceutical and healthcare concerns. However impressive these companies are, though (and they are), they are not sequencing the human genome. Because they're not, the output of these competitors may actually prove to be complementary to Celera's ambitions, rather than combative. Focused genetic information created by these companies could serve to complement Celera's genome information.

Whether or not this proves accurate, we still see any genetic-based companies as potential competitors. But there is only one large competitor in the minds of many. If the government's Human Genome Project provides a free map of the human genome to the public, as it plans to, then Celera, in trying to sell its information, will compete directly with the federal government and its free data. Many people see this possibility as a significant strike against Celera. Perhaps it will be.

Then again, consider Linux software. Linux is freeware (like genome data might be), but there is tremendous value being created by Rule Breakers, such as Red Hat Software (Nasdaq: RHAT), that offer Linux-related services and value-added Linux products. In similar fashion, Celera will likely offer the most detailed genome information, and it will offer it with an unmatched level of expertise. Celera will be paid to help clients actually make use of complex genome data. Creating a business this way, Celera can, and will, give genome data away for free, too, thereby lessening our fear that the Human Genome Project can harm it. (Celera charges for the right to preview the fruit fly genome, but soon the company will distribute the information freely and charge for services related to it.)

So, Celera has the best technology and management (as we'll see in a moment) and this gives it numerous advantages over competition, but is the competition inept? Not by any means. Although we can't say that Celera has inept competition, given Celera's gene-sequencing lab (the most advanced in the world), and provided its jump on the competition (already!), we can say that Celera and its technology is making the competition look much less imposing.

However, Celera can't succeed on rooms filled with cool technology alone. The company spends over $65,000 a month on its electric bill. It needs cash. Luckily, it has cash. While the competition is typically strapped for greenbacks, Celera recently had over $200 million in cash and it will be paid over $75 million by its sister company, PE Biosystems (NYSE: PEB), over the next three years. This should be enough money to fund Celera's operations beyond 2001, and by the end of that year Celera plans to have the human genome mapped and several more paying business partners feeding the company coffers.

After mapping the human gene sequence, Celera will begin to map the genomes of the next species up the ladder, the rat. (OK, bad joke there, but it's true that the rat is next.) The rat is to be followed by the mouse and agricultural species, including rice and maize. Interest in information on these species will span several industries all around the globe. (How to make stronger corn will interest Iowa. How to make rats shrink will interest the city of New York.) All told, Celera will strive to build itself as the predominant genome information portal in the world, offering details and analysis on genome data for anything from salmon, to beets, to perhaps Grizzly Bear.

You can only imagine the revenue potentials of offering such a massive amount of varied and powerful (almost frighteningly so) information. (Industry estimates are all in the billions.) Clearly, the human genome promises to be the most helpful to humans for its ability to help scientists cure disease, but at the same time, we will be able to make food much more tasty in years ahead, and that ain't a bad benefit either. Food companies will pay for this advantage. This is all a roundabout way of saying that there isn't obvious competition on the horizon that stands to get in Celera's way as it begins to "map" the entire living world. Nobody has the computational power, the management, and the speed that Celera is showing.

Then there are patents. Some Fools have been concerned that Celera may not be at the forefront in obtaining patents. Competitors have literally filed for tens of thousands of patents while Celera, at recent count, had filed for about 7,000 gene patents. Other Fools wonder if Celera will be able to patent the human genome, or other gene sequences, at all. After all, who really owns this information? A God somewhere on high? Maybe. So, who will be allowed to own the information down here on Earth? That question could be decided by the courts, and some people believe the court will not allow anyone to own the information. We think differently. In healthcare so far, we've seen that discovering companies are given the right to patent scientific information that they unravel. Genes don't appear to be any different.

While we do believe that the discovering company will own the patent to the human genome, we don't believe that a patent on the information will be vitally important anyway. Celera will be selling smart information, not mere strands of letters the likes of which anyone could theoretically copy. The company will sell its expertise -- an expertise aided by its having the most precise genome information organized in the most useful form, and from employing many of the smartest scientists in the world. Patents or not, Celera stands to possess more genetic information than any other company, and, presumably having discovered it, it will have inherent rights in how to organize, manage, analyze, utilize, and distribute it. Celera plans to patent 300 specific genes of the human genome as well as the process of using them, and we don't see anybody stopping this. (For excellent thoughts regarding patent issues further, see this post by Fool ElricSeven.)

When it comes to business momentum, Celera -- Mr. SPEED -- has it. Recently up and running, the company already completed the sequencing phase of the fruit fly genome by sequencing more than 1.8 billion base pairs by September. Celera did more sequencing in nine months than other companies have completed in a decade. Assembly of the genome should be done before 2000. Celera's sequencing of the fruit fly in under a year serves as "proof in the pudding," so to speak, that the company is able to quickly construct genomic DNA in its new lab.

The fruit fly genome is much larger than any other genome sequenced in all of history, so to complete it so quickly is revolutionary. (Right now Celera is gunning through the human genome.) Thus, Celera has more "momentum" -- more SPEED -- than any other company that we've ever bought. Human Genome Sciences and Incyte required several years to sequence less than 10% of the human genome. Celera is hoping to do the whole shebang in under 27 months, and is already well on its way.

So, other than visionary management, which we address next, criteria number two is now complete. Celera has a sustainable advantage due to technology and its brain trust. It has seemingly unsurpassable business momentum due to the same and its speed. It does have competition, namely from the government, and large questions remain regarding how much money Celera can earn from its information if the government provides similar information for free. We're betting on Celera's proprietary expertise and detailed knowledge to sell, though, and we believe that we're already seeing this happen via the partnerships Celera is signing with firms like Pfizer. We're also betting that Celera's genome data quality will top that of its competition, largely due to the same two advantages already mentioned, technology and management. As for patents: intellectual property abounds at Celera, and with it patents will, too. The company has been filing for patents steadily, and it will continue at a regular and likely increased pace. This baby has several moats built around its business, and the sustainable advantages of a true Rule Breaker.

Karyotype stability

With the exception of the chromosome 9–10 fusion, X. laevis and X. tropicalis chromosomes have maintained conserved synteny since their divergence around 48 Ma (Fig. 1a, b). The absence of inter-chromosomal rearrangements is consistent with the relative stability of amphibian and avian karyotypes compared to those of mammals 25 , which typically show dozens of inter-chromosome rearrangements 26 . It also contrasts with many plant polyploids, which can show considerable inter-subgenome rearrangement 27 . The distribution of L- and S-specific repeats along entire chromosomes implies the absence of crossover recombination between homoeologues since allotetraploidization, presumably because the two progenitors were sufficiently diverged to avoid meiotic pairing between homoeologous chromosomes, though we cannot rule out very limited localized inter-homoeologue exchanges (Supplementary Note 7).

The extensive collinearity between homologous X. laevis L and X. tropicalis chromosomes (Fig. 1a) implies that they represent the ancestral chromosome organization. In contrast, the S subgenome shows extensive intra-chromosomal rearrangements, evident in the large inversions of XLA2S, XLA3S, XLA4S, XLA5S and XLA8S, as well as shorter rearrangements (Fig. 1a). The S subgenome has also experienced more deletions. For example, the 45S pre-ribosomal RNA gene cluster is found on X. laevis XLA3Lp, but its homoeologous locus on XLA3Sp is absent (Extended Data Fig. 5a). Extensive small-scale deletions (Extended Data Fig. 5b) reduce the length of S chromosomes relative to their L and X. tropicalis counterparts (see below).


These frogs are plentiful in ponds and rivers within the south-eastern portion of Sub-Saharan Africa. They are aquatic and are often greenish-grey in color. African clawed frogs are also frequently sold as pets, and sometimes incorrectly misidentified as African dwarf frogs. Albino clawed frogs are common and sold as pets or for laboratories.

They reproduce by fertilizing eggs outside of the female's body (see frog reproduction). Of the seven amplexus modes (positions in which frogs mate), these frogs are found breeding in inguinal amplexus, where the male clasps the female in front of the female's back legs and squeezes until eggs come out. The male then sprays sperm over the eggs to fertilize them.

African clawed frogs are highly adaptable and will lay their eggs whenever conditions allow it. During wet rainy seasons they will travel to other ponds or puddles of water to search for food. [4] During times of drought, the clawed frogs can burrow themselves into the mud, becoming dormant for up to a year. [5]

Xenopus laevis have been known to survive 15 or more years in the wild and 25–30 years in captivity. [6] They shed their skin every season, and eat their own shed skin.

Although lacking a vocal sac, the males make a mating call of alternating long and short trills, by contracting the intrinsic laryngeal muscles. Females also answer vocally, signaling either acceptance (a rapping sound) or rejection (slow ticking) of the male. [7] [8] This frog has smooth slippery skin which is multicolored on its back with blotches of olive gray or brown. The underside is creamy white with a yellow tinge.

Male and female frogs can be easily distinguished through the following differences. Male frogs are small and slim, while females are larger and more rotund. Males have black patches on their hands and arms which aid in grabbing onto females during amplexus. Females have a more pronounced cloaca and have hip-like bulges above their rear legs where their eggs are internally located.

Both males and females have a cloaca, which is a chamber through which digestive and urinary wastes pass and through which the reproductive systems also empty. The cloaca empties by way of the vent which in reptiles and amphibians is a single opening for all three systems. [9]

African clawed frogs are fully aquatic and will rarely leave the water except to migrate to new water bodies during droughts or other disturbances. Clawed frogs have powerful legs that help them move quickly both underwater and on land. Feral clawed frogs in South Wales have been found to travel up to 2 kilometres (1.2 mi) between locations. [10] The feet of Xenopus species have three black claws on the last three digits. These claws are used to rip apart food and scratch predators.

Clawed frogs are carnivores and will eat both living and dead prey including fish, tadpoles, crustaceans, annelids, arthropods, and more. Clawed frogs will try to consume anything that is able to fit into their mouths. Being aquatic, clawed frogs use their sense of smell and their lateral line to detect prey rather than eyesight like other frogs. However, clawed frogs can still see using their eyes and will stalk prey or watch predators by sticking their heads out of the water. [11] Clawed frogs will dig through substrate to unearth worms and other food. Their tongue is unable to extend like other frogs, so clawed frogs use their hands to grab food and shovel it into their mouths.

These frogs are particularly cannibalistic the stomach contents of feral clawed frogs in California have revealed large amounts of the frog's larvae. [12] Clawed frog larvae are filter feeders and collect nutrients from plankton, allowing adult frogs that consume the tadpoles to have access to these nutrients. This allows clawed frogs to survive in areas that have little to no other food sources.

Clawed frogs are nocturnal and most reproductive activity and feeding occurs after dark. Male clawed frogs are very promiscuous and will grab onto other males and even other species of frogs. [13] [14] Male frogs that are grasped will make release calls and attempt to break free.

If not feeding, clawed frogs will just sit motionless on top of the substrate or floating at the top with their heads sticking out.

In the wild, Xenopus laevis are native to wetlands, ponds, and lakes across arid/semiarid regions of Sub-Saharan Africa. [2] [16] Xenopus laevis and Xenopus muelleri occur along the western boundary of the Great African Rift. The people of the sub-Saharan are generally very familiar with this frog, and some cultures use it as a source of protein, an aphrodisiac, or as fertility medicine. Two historic outbreaks of priapism have been linked to consumption of frog legs from frogs that ate insects containing cantharidin. [17]

Xenopus laevis in the wild are commonly infected by various parasites, [15] including monogeneans in the urinary bladder.

Xenopus embryos and eggs are a popular model system for a wide variety of biological studies, in part because they have the potential to lay eggs throughout the year. [18] [19] [20] This animal is widely used because of its powerful combination of experimental tractability and close evolutionary relationship with humans, at least compared to many model organisms. [18] [19] For a more comprehensive discussion of the use of these frogs in biomedical research, see Xenopus.

Xenopus laevis is also notable for its use in the first widely used method of pregnancy testing. In the 1930s, two South African researchers, Hillel Shapiro and Harry Zwarenstein, [21] students of Lancelot Hogben at the University of Cape Town, discovered that the urine from pregnant women would induce oocyte production in X. laevis within 8–12 hours of injection. [22] This was used as a simple and reliable test up through to the 1960s. [23] In the late 1940s, Carlos Galli Mainini [24] found in separate studies that male specimens of Xenopus and Bufo could be used to indicate pregnancy [25] Today, commercially available hCG is injected into Xenopus males and females to induce mating behavior and to breed these frogs in captivity at any time of the year. [26]

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 the only vertebrate model system that allows for high-throughput in vivo analyses of gene function and high-throughput biochemistry. Finally, Xenopus oocytes are a leading system for studies of ion transport and channel physiology. [18]

Although X. laevis does not have the short generation time and genetic simplicity generally desired in genetic model organisms, it is an important model organism in developmental biology, cell biology, toxicology and neurobiology. X. laevis takes 1 to 2 years to reach sexual maturity and, like most of its genus, it is tetraploid. It does have a large and easily manipulated embryo, however. The ease of manipulation in amphibian embryos has given them an important place in historical and modern developmental biology. A related species, Xenopus tropicalis, is now being promoted as a more viable model for genetics.

Roger Wolcott Sperry used X. laevis for his famous experiments describing the development of the visual system. These experiments led to the formulation of the Chemoaffinity hypothesis.

Xenopus oocytes provide an important expression system for molecular biology. By injecting DNA or mRNA into the oocyte or developing embryo, scientists can study the protein products in a controlled system. This allows rapid functional expression of manipulated DNAs (or mRNA). This is particularly useful in electrophysiology, where the ease of recording from the oocyte makes expression of membrane channels attractive. One challenge of oocyte work is eliminating native proteins that might confound results, such as membrane channels native to the oocyte. Translation of proteins can be blocked or splicing of pre-mRNA can be modified by injection of Morpholino antisense oligos into the oocyte (for distribution throughout the embryo) or early embryo (for distribution only into daughter cells of the injected cell). [27]

Extracts from the eggs of X. laevis frogs are also commonly used for biochemical studies of DNA replication and repair, as these extracts fully support DNA replication and other related processes in a cell-free environment which allows easier manipulation. [28]

The first vertebrate ever to be cloned was an African clawed frog in 1962, [29] an experiment for which Sir John Gurdon was awarded the Nobel Prize in Physiology or Medicine in 2012 "for the discovery that mature cells can be reprogrammed to become pluripotent". [30]

Additionally, several African clawed frogs were present on the Space Shuttle Endeavour (which was launched into space on September 12, 1992) so that scientists could test whether reproduction and development could occur normally in zero gravity. [31] [32]

Xenopus laevis also serves as an ideal model system for the study of the mechanisms of apoptosis. In fact, iodine and thyroxine stimulate the spectacular apoptosis of the cells of the larval gills, tail and fins in amphibians metamorphosis, and stimulate the evolution of their nervous system transforming the aquatic, vegetarian tadpole into the terrestrial, carnivorous frog. [33] [34] [35] [36]

Stem cells of this frog were used to create xenobots.

Genome sequencing Edit

Early work on sequencing of the X. laevis genome was started when the Wallingford and Marcotte labs obtained funding from the Texas Institute for Drug and Diagnostic Development (TI3D), in conjunction with projects funded by the National Institutes of Health. The work rapidly expanded to include de novo reconstruction of X. laevis transcripts, in collaboration with groups around the world donating Illumina Hi-Seq RNA sequencing datasets. Genome sequencing by the Rokhsar and Harland groups (UC Berkeley) and by Taira and collaborators (University of Tokyo, Japan) gave a major boost to the project, which, with additional contributions from investigators in the Netherlands, Korea, Canada and Australia, led to publication of the genome sequence and its characterization in 2016. [37]

Xenbase [38] is the Model Organism Database (MOD) for both Xenopus laevis and Xenopus tropicalis. [39] Xenbase hosts the full details and release information regarding the current Xenopus laevis genome (9.1).

Xenopus laevis have been kept as pets and research subjects since as early as the 1950s. They are extremely hardy and long lived, having been known to live up to 20 or even 30 years in captivity. [40]

African clawed frogs are frequently mislabeled as African dwarf frogs in pet stores. Identifiable differences are:

  • Dwarf frogs have four webbed feet. African clawed frogs have webbed hind feet while their front feet have autonomous digits.
  • African dwarf frogs have eyes positioned on the side of their head, while African clawed frogs have eyes on the top of their heads.
  • African clawed frogs have curved, flat snouts. The snout of an African dwarf frog is pointed.

African clawed frogs are voracious predators and easily adapt to many habitats. [41] For this reason, they can easily become a harmful invasive species. They can travel short distances to other bodies of water, and some have even been documented to survive mild freezes. They have been shown to devastate native populations of frogs and other creatures by eating their young.

In 2003, Xenopus laevis frogs were discovered in a pond at San Francisco's Golden Gate Park. Much debate now exists in the area on how to exterminate these creatures and keep them from spreading. [42] [43] It is unknown if these frogs entered the San Francisco ecosystem through intentional release or escape into the wild. San Francisco officials drained Lily Pond and fenced off the area to prevent the frogs from escaping to other ponds in the hopes they starve to death.

Due to incidents in which these frogs were released and allowed to escape into the wild, African clawed frogs are illegal to own, transport or sell without a permit in the following US states: Arizona, California, Kentucky, Louisiana, New Jersey, North Carolina, Oregon, Vermont, Virginia, Hawaii, [44] Nevada, and Washington state. However, it is legal to own Xenopus laevis in New Brunswick (Canada) and Ohio. [45] [46]

Feral colonies of Xenopus laevis exist in South Wales, United Kingdom. [47] In Yunnan, China there is a population of albino clawed frogs in Lake Kunming, along with another invasive: the American bullfrog. Because this population is albino, it suggests that the clawed frogs originated from the pet trade or a laboratory. [48]

The African clawed frog may be an important vector and the initial source of Batrachochytrium dendrobatidis, a chytrid fungus that has been implicated in the drastic decline in amphibian populations in many parts of the world. [2] Unlike in many other amphibian species (including the closely related western clawed frog) where this chytrid fungus causes the disease Chytridiomycosis, it does not appear to affect the African clawed frog, making it an effective carrier. [2]

What are Frog Blood Cells

Frog blood cells refer to the circulating cells in the frog blood. Though humans and other mammals are warm-blooded animals, fish, and amphibians such as frog, and reptiles are cold-blooded animals. This means they rely on external heat to heat up their blood. The heart of the frogs consists of three chambers: two atria and a single ventricle. Oxygenated blood is mixed with deoxygenated blood to some extent in the frog’s heart. Therefore, frogs have to maintain a slow metabolic rate in their body. Frogs absorb some amount of oxygen through their skin as well. Frogs have red blood cells and white blood cells in their blood. The red blood cells of frogs are shown in figure 4.

Figure 4: Frog Red Blood Cells under x1000 Magnification

The red blood cells of frogs are quite larger than human red blood cells. They are also somewhat elliptical than human red blood cells. Unlike humans (mammals), fish, amphibian, reptile, and avian red blood cells consist of a single nucleus per cell. The white blood cells of frogs are more similar to that of humans in both morphology and function. However, frogs lack platelets in their blood.


Sodir NM, Swigart LB, Karnezis AN, Hanahan D, Evan GI, Soucek L: Endogenous Myc maintains the tumor microenvironment. Genes Dev. 2011, 25: 907-1016. 10.1101/gad.2038411.

Li Y, Zheng H, Luo R, Wu H, Zhu H, Li R, Cao H, Wu B, Huang S, Shao H, Ma H, Zhang F, Feng S, Zhang W, Du H, Tian G, Li J, Zhang X, Li S, Bolund L, Kristiansen K, de Smith AJ, Blakemore AI, Coin LJ, Yang H, Wang J, Wang J: Structural variation in two human genomes mapped at single-nucleotide resolution by whole genome de novo assembly. Nat Biotechnol. 2011, 29: 723-730. 10.1038/nbt.1904.

Keane TM, Goodstadt L, Danecek P, White MA, Wong K, Yalcin B, Heger A, Agam A, Slater G, Goodson M, Furlotte NA, Eskin E, Nellåker C, Whitley H, Cleak J, Janowitz D, Hernandez-Pliego P, Edwards A, Belgard TG, Oliver PL, McIntyre RE, Bhomra A, Nicod J, Gan X, Yuan W, van der Weyden L, Steward CA, Bala S, Stalker J, Mott R, et al: Mouse genomic variation and its effect on phenotypes and gene regulation. Nature. 2011, 477: 289-294. 10.1038/nature10413.

Khatib F, DiMaio F, Foldit Contenders Group Foldit Void Crushers Group, Cooper S, Kazmierczyk M, Gilski M, Krzywda S, Zabranska H, Pichova I, Thompson J, Popović Z, Jaskolski M, Baker D: Crystal structure of a monomeric retroviral protease solved by protein folding game players. Nat Struct Mol Biol. 2011, 18: 1175-1177. 10.1038/nsmb.2119.

Good BM, Su AI: Games with a scientific purpose. Genome Biol. 2011, 12: 135-10.1186/gb-2011-12-12-135.

Stephens PJ, Greenman CD, Fu B, Yang F, Bignell GR, Mudie LJ, Pleasance ED, Lau KW, Beare D, Stebbings LA, McLaren S, Lin ML, McBride DJ, Varela I, Nik-Zainal S, Leroy C, Jia M, Menzies A, Butler AP, Teague JW, Quail MA, Burton J, Swerdlow H, Carter NP, Morsberger LA, Iacobuzio-Donahue C, Follows GA, Green AR, Flanagan AM, Stratton MR, et al: Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011, 144: 27-40. 10.1016/j.cell.2010.11.055.

Zhu Q, Pao GM, Huynh AM, Suh H, Tonnu N, Nederlof PM, Gage FH, Verma IM: BRCA1 tumour suppression occurs via heterochromatin-mediated silencing. Nature. 2011, 477: 179-184. 10.1038/nature10371.

Ravel J, Gajer P, Abdo Z, Schneider GM, Koenig SS, McCulle SL, Karlebach S, Gorle R, Russell J, Tacket CO, Brotman RM, Davis CC, Ault K, Peralta L, Forney LJ: Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci USA. 2011, 108 (Suppl 1): 4680-4687.

Kagey MH, Newman JJ, Bilodeau S, Zhan Y, Orlando DA, van Berkum NL, Ebmeier CC, Goossens J, Rahl PB, Levine SS, Taatjes DJ, Dekker J, Young RA: Mediator and cohesin connect gene expression and chromatin architecture. Nature. 2010, 467: 430-5. 10.1038/nature09380.

Chu C, Qu K, Zhong FL, Artandi SE, Chang HY: Genomic maps of long noncoding RNA occupancy reveal principles of RNA-chromatin interactions. Mol Cell. 2011, 44: 667-678. 10.1016/j.molcel.2011.08.027.

Berman BP, Weisenberger DJ, Aman JF, Hinoue T, Ramjan Z, Liu Y, Noushmehr H, Lange CP, van Dijk CM, Tollenaar RA, Van Den Berg D, Laird PW: Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Nat Genet. 2011,

McGary KL, Park TJ, Woods JO, Cha HJ, Wallingford JB, Marcotte EM: Systematic discovery of nonobvious human disease models through orthologous phenotypes. Proc Natl Acad Sci USA. 2010, 107: 6544-6549. 10.1073/pnas.0910200107.

Jiang L, Schlesinger F, Davis CA, Zhang Y, Li R, Salit M, Gingeras TR, Oliver B: Synthetic spike-in standards for RNA-seq experiments. Genome Res. 2011, 21: 1543-1551. 10.1101/gr.121095.111.

Heo JB, Sung S: Vernalization-mediated epigenetic silencing by a long intronic noncoding RNA. Science. 2011, 331: 76-79. 10.1126/science.1197349.

Angel A, Song J, Dean C, Howard M: A polycomb-based switch underlying quantitative epigenetic memory. Nature. 2011, 476: 105-108. 10.1038/nature10241.

Secrets to 'extreme adaptation' found in Burmese python genome

The Burmese python's ability to ramp up its metabolism and enlarge its organs to swallow and digest prey whole can be traced to unusually rapid evolution and specialized adaptations of its genes and the way they work, an international team of biologists says in a new paper.

Lead author Todd Castoe, an assistant professor of biology at The University of Texas at Arlington College of Science, and 38 co-authors from four countries sequenced and analyzed the genome of the Burmese python, or Python molurus bivittatus. Their work is scheduled for publication this week (Dec. 2) by the Proceedings of the National Academy of Sciences along with a companion paper on the sequencing and analysis of the king cobra (Ophiophagus hannah). The papers represent the first complete and annotated snake genomes.

Because snakes contain many of the same genes as other vertebrates, studying how these genes have evolved to produce such extreme and unique characteristics in snakes can eventually help explain how these genes function, including how they enable extreme feats of organ remodeling. Such knowledge may eventually be used to treat human diseases.

"One of the fundamental questions of evolutionary biology is how vertebrates with all the same genes display such vastly different characteristics. The Burmese python is a great way to study that because it is so extreme," Castoe, who began working on the python project as a postdoctoral fellow at the University of Colorado School of Medicine in the laboratory of associate professor and paper corresponding author David D. Pollock.

Castoe said: "We'd like to know how the snake uses genes we all have to do things that no other vertebrates can do."

The new python study calls into question previous theories that major obvious physical differences among species are caused primarily by changes in gene expression. Instead, it contends that protein adaptation, gene expression and changes in the structure of the organization of the genome itself are all at work together in determining the unusual characteristics that define snakes, and possibly other vertebrates.

Pollock said the python and king cobra studies represent a significant addition to the field of "comparative systems genomics -- the evolutionary analysis of multiple vertebrate genomes to understand how entire systems of interacting genes can evolve from the molecules on up."

He said: "I believe that such studies are going to be fundamental to our ability to understand what the genes in the human genome do, their functional mechanisms, and how and why they came to be structured the way they are."

The Burmese python's phenotype, or physical characteristics, represents one of the most extreme examples of evolutionary adaptation, the authors said. Like all snakes, its evolutionary origin included reduction in function of one lung and the elongation of its mid-section, skeleton and organs. It also has an extraordinary ability for what researchers call "physiological remodeling."

Physiological remodeling refers to the process by which pythons are able to digest meals much larger than their size, such as chickens or piglets, by ramping up their metabolism and increasing the mass of their heart, liver, small intestine and kidneys 35 percent to 150 percent in only 24 to 48 hours. As the digestion is completed, the organs return to their original size within a matter of days. The authors suggest that understanding how snakes accomplish these tremendous feats could hold vital clues for the development of treatments for many different types of human diseases.

"The Burmese python has an amazing physiology. With its genome in hand, we can now explore the many untapped molecular mechanisms it uses to dramatically increase metabolic rate, to shut down acid production, to improve intestinal function, and to rapidly increase the size of its heart, intestine, pancreas, liver, and kidneys," said Stephen Secor, associate professor of biological sciences at the University of Alabama and a co-author on the paper. 'The benefits of these discoveries transcends to the treatment of metabolic diseases, ulcers, intestinal malabsorption, Crohn's disease, cardiac hypertrophy and the loss of organ performance."

To complete their work, the research team aligned 7,442 genes from the python and cobra with genes sequences available in the Ensembl Genome Browser from other amphibians, reptile, bird and mammals. They used a statistical method called "branch site codon modeling" to look for genes that had been positively selected (or evolutionarily changed due to natural selection) in the python, the cobra, and early in snake evolution in the common ancestor of these two snakes. They found changes in hundreds of genes. They believe the results demonstrate that natural selection-driven changes in many genes that encode proteins contributed substantially to the unique characteristics of snakes.

Analyses showed a remarkable correspondence between the function of the selected genes, and the many functionally unique aspects of snake biology -- such as their unique metabolism, spine and skull shape and cell cycle regulation, Castoe said. Many of the altered genes the team observed also have prominent medical significance. For example, the python genome showed some changes to the gene GAB1, which other research suggests plays a role in breast cancer, melanomas and childhood leukemia.

In addition to changes to individual genes and their expression, researchers also found that the extreme characteristics in snakes could also be linked to duplications or losses in multigene families. Some of those include ancient loss and more recent re-evolution of high resolution vision, and their ability to detect chemical cues from the environment. Researchers also observed that, while most assume that reptile genes and genomes change at a very slow rate, snake genomes evolve at one of the fastest rates of any vertebrate.

Alex Long, '17

Alex Long, 󈧕, came to Richmond set on studying to become a doctor. He assumed he would conduct undergraduate research related to human biology, working toward his goal of attending medical school. So how did he wind up studying frog speciation

After taking biology professor Rafael de Sà’s evolution class and loving it, someone mentioned to Long that de Sà had an opening in his lab.

De Sà has spent the past 25 years studying frog speciation, using DNA sequencing to determine subtle genetic and physical differences between species, including some that may not even be visible. His most recent project involved gathering specimens of humming frogs in the Atlantic Forest in Brazil and mapping their DNA. He wanted to determine if they were all part of one large species, or if there were several smaller species contained within the large group.

“I didn’t care that we were working with frogs, rather than on human biology,” Long said. “I knew he was the mentor that I wanted.”

Long came into the lab as a few other students were graduating, which gave him the opportunity to learn from them before taking a leadership role after they left. The summer after his sophomore year, he was able to go to a conference with Dr. de Sà where the two learned about a technique called next generation sequencing, which uses the computer program Linux to run the same DNA sequencing that de Sà had been using, only with faster results. “It gives you a tree at the end of speciation with such precision and accuracy that it’s leaps and bounds ahead of anything that had been done here previously,” Long said.

The only problem: no one in de Sà’s lab knew how to use Linux. “My previous computer experience was basically being really good at Microsoft Office,” Long joked. “But because I knew how much this project meant to the lab, and I saw it’s potential, I taught myself to use Linux so that I could take all of the samples that we had from Brazil and run them through the program.”

Long’s efforts paid off. “At the end of the initial computer sequencing, we came out with three new species of frogs, with incredible precision and statistical confidence in our data,” he said. “The potential of our work makes me happy, and I’m happy to be part of Dr. de Sa’s research because of how much he cares about it.”

Long says his time in de Sà’s lab has also reinforced his love for science. “People have to put in the work, and spend their whole lives devoted to their passion, and after seeing that in Dr. de Sà, I realized that it’s reassuring that we have scientists to take these niche jobs and interests to make sure knowledge is proliferating,” Long said.

Long is still planning on going to medical school, but with three years before his MCAT score expires, he decided to take a detour. He’ll pursue a master’s degree in biomedical science policy and advocacy at Georgetown. “This program focuses on the policy aspects and how you can talk to people about science it can be a scary time to be a scientist, which is why I’m excited to learn how to advocate for myself and other scientists make sure that research and data sets aren’t lost, and that research programs aren’t shut down.”

While Long didn’t anticipate the research path he would take, he’s grateful for all he’s gained. “Through this experience, I got to learn more than I ever thought I learned about molecular biology, computations, and ecology, and I taught myself to use a software program I had no familiarity with.”

He also sees the bigger picture of how his work might play a larger role in animal conservation. “If we find a frog species that hasn’t been previously defined, and it’s in a very small pocket of land in Brazil, we have the information to advocate to protect that land because it houses an endangered species,” he said.

Watch the video: Ο πρόεδρος της Bayer Ph. παραδέχεται ότι τα εμβόλια mRNA είναι Κυτταρική και Γονιδιακή Θεραπεία (May 2022).


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