Mexican salamander helps uncover mysteries of stem cells and evolution

Jul 11, 2010

Dr Andrew Johnson is speaking today at the UK National Stem Cell Network annual conference. He and his team from the University of Nottingham have been using a Mexican aquatic salamander called an axolotl to study the evolution and genetics of stem cells - research that supports the development of regenerative medicine to treat the consequences of disease and injury using stem cell therapies. This team has found that there are extraordinary similarities in the development of axolotls and mammals that provide unique opportunities to study the properties of embryonic stem cells and germ cells. These findings are underpinned by a novel theory of evolution that unifies the diversity of mechanisms in animal developmental into a single conceptual framework.

Dr Johnson said "We've produced evidence that pluripotency - the ability of an embryonic stem cell to become absolutely any kind of cell - is actually very ancient in evolutionary terms. Even though received wisdom is that it evolved with mammals, our research suggests that it was there all along, just not in many of the species that people use in the lab. In fact, probably exist in the embryos of the simple animals from which amphibians evolved.

"Axolotls, unlike many of the frogs, fish, flies and worms that are used in the lab, have pluripotent cells in their embryos that are the equivalent to those found in embryos from mammals, in that they can produce germ cells, in addition to somatic cells, a property known as ground-state pluripotency. And from a practical perspective, axolotl embryos will provide a very useful tool for understanding how to manipulate embryonic stem cells for modern regenerative medicine."

Axolotls are that retained primitive characteristics of the first amphibians, the animals descended from fish that moved onto land about 385 million years ago. These early amphibians were the ancestors of every land dwelling vertebrate, including humans. This places axolotls in a perfect position to understand how vertebrates evolved on land.

Dr Johnson continued "We've found that the genetic mechanisms controlling the development of salamander embryos were not changed as amphibian embryos evolved into those of reptiles and then, later, mammals. This explains why newts (salamanders) look so much like lizards (reptiles), and since mammals evolved directly from reptiles it makes sense that the genetic mechanisms controlling embryo development remain largely unchanged from axolotls to humans. Axolotl embryos are therefore far more similar to those of humans than the more commonly studied embryos of frogs and fish that most development researchers use.

"We recently found out that pluripotency in axolotls and mammals depends on a gene called Nanog, which frogs do not have. Therefore we think that the Nanog gene was lost from the frog genome after frogs and salamanders evolved separately from their common amphibian ancestor. This is contrary to a long-held opinion that ground-state pluripotency evolved with mammals and suggests that pluripotency could actually be one of the most ancient features of embryos. But since depends on generating advantageous changes, and pluripotency seems to be a good thing - we had to ask ourselves why would frogs have lost the Nanog gene, and with it pluripotency?""

Through work to explore why frogs might have lost pluripotency Dr Johnson and colleagues developed a new theory of evolution in 2003. This theory says that a key driver of vertebrate evolution is the relationship of the germ cells, which become sperm and egg, and the rest of the body, called the soma.

Dr Johnson said "The reason that losing pluripotency would have been an advantage to frogs, for example, is that it has actually made it possible for them to diverge into numerous closely related species - it is possible for them to make far more frequent fairly subtle changes in the evolution of their body shape and physiology. In axolotls and humans it has been necessary to keep a far more rigid arrangement of the soma and therefore they have not diverged into multiple closely related species. And the reason for this is that there are two quite different ways of producing germ cells."

The embryos of most lab animals, including frogs but not mice, contain material called germ plasm, and germ plasm has the role of instructing cells to become the primordial germ cells which go on to become sperm and egg. But axolotls are different; Dr Johnson's team found that their embryos actually don't contain germ plasm and instead they use a system very similar to mice and humans. Axolotls produce their primordial germs cells from pluripotent cells - similar to - by a process called induction.

Dr Johnson said "Within our new theory of evolution pluripotency came first and so germ plasm would have to have evolved independently several times in species within the branches of the tree, for example in frogs and many fish. This is a process called convergent evolution - where a common advantage leads to several species developing features that make them appear more similar, rather than less.

"What is the advantage of germ plasm such that it would have evolved several times? We had to resolve the argument that germ plasm wasn't necessary because pluripotency did the job just fine. We knew that with germ plasm pluripotency is not necessary, because the embryos contain primordial germ cells anyway. This explains why the Nanog gene became dispensable, and was lost from the DNA but it doesn't explain what is the advantage to having germ plasm."

Dr. Johnson and his colleagues suggest that the evolution of germ plasm liberates the soma of an organism to evolve more rapidly, simply because the embryo doesn't need to induce germ cells - they are already there because of germ plasm. As a result of this, the genetic mechanisms that control the soma are free to evolve, because they are no longer occupied with producing the signals that induce primordial from pluripotent embryonic cells.

Dr Johnson concluded "Organisms with germ plasm evolve more rapidly, and produce more species than those without it because there is a great deal more genetic flexibility. So, in the case of frogs, the selective advantage to having lost pluripotency in favour of germ plasm is the freedom to evolve many more species of frogs, which can inhabit many different environments. The down side is that once frogs evolved they never gave rise to anything but other frogs. On the other hand, because salamander contain pluripotent cells they had the raw material to evolve completely new structures such as extraembryonic membranes, which are fundamental to the development of reptiles and mammals.

"We think that ultimately, the germ line-soma relationship is likely to be a major contributor to the astonishing diversity of species that inhabit the earth."

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kevinrtrs
1 / 5 (3) Jul 12, 2010
But since evolution depends on generating advantageous changes,

How many recorded advantageous changes have been observed in the past 100 years since evolutionary theory came to the fore?
If evolution is to proceed at a believable rate then such advantageous changes need to be visible over even a short timespan of 100 years. Otherwise it will never reach the kind of metamorphic outcomes that are currently ascribed to it - even over 4.5 Billion years.

In axolotls and humans it has been necessary to keep a far more rigid arrangement of the soma

Why does it have to be NECESSARY? I thought evolution occurred as a result of random changes? For something to be necessary requires that a purpose or a specified objective exists beforehand.
Evolutionary theory cannot have such predetermined specified objective - otherwise it would mean that an intelligent agent is/was present, something that evolutionary theory specifically excludes.

Decide which it is:Random/Planned.
Skeptic_Heretic
5 / 5 (2) Jul 12, 2010
How many recorded advantageous changes have been observed in the past 100 years since evolutionary theory came to the fore?
If evolution is to proceed at a believable rate then such advantageous changes need to be visible over even a short timespan of 100 years. Otherwise it will never reach the kind of metamorphic outcomes that are currently ascribed to it - even over 4.5 Billion years.
Many millions of changes have been recorded, none have been given the moniker of advantageous or detrimental as either is a value judgement when decoupled from the environment. Many examples of mutation have been found within human beings. For example, the gene mutation that inhibits myelin production allows for super musculature in human beings. We've found genetic mutation that enable Ultraviolet spectrum vision in some women. We've found human beings with advanced resistance to AIDS and HIV.

Just because you don't understand it doesn't mean it isn't happening.
LivaN
not rated yet Jul 12, 2010
???????????????
I exist.
I deem that it was necessary for humanity to exist prior to my existence.
Before humanity existed, it had the purpose/ objective of creating me, as it will inevitably be deemed necessary by me for my existence, and as we all know:

For something to be necessary requires that a purpose or a specified objective exists beforehand. Things cannot be deemed necessary, in hindsight, for the current state of affairs.

Therefore I “Planned” my existence, which is deemed necessary by my children.
frajo
not rated yet Jul 12, 2010
We've found genetic mutation that enable Ultraviolet spectrum vision in some women.
Human tetrachromacy remains to be confirmed. It doesn't suffice to have a fourth kind of cone in the retina. In order to exhibit full-fledged tetrachromacy like (most) birds, the retinal neurons, the optic nerve, and the brain must have corresponding processing capacities. None of it has yet been shown to exist.
jmcanoy1860
5 / 5 (2) Jul 14, 2010
Ok, if you don't like getting coned try lactose tolerance in caucasians. Citrate utilization in E.Coli. Mutations related to hyperdense bones in humans (read: sturdy.

The reason why no one hears of millions of "beneficial mutations" is simply because they are deemed normal variants especially if the mutation is only important in the elderly. No one reports them in a manner related to evolution. Check out the medical literature and you will find mutations of many kinds and flavors.

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