Chimeras on the loose.

[jimmy olsen]

I know this story is old, but I think it's pretty cool and really, how many of you are that up to date on the genetics of the Marmoset?

http://www.nytimes.com/2007/03/27/science/27marm.html

In the Marmoset Family, Things Really Do Appear to Be All Relative

By CARL ZIMMER
Published: March 27, 2007

"Well, I'll be a monkey's uncle" has now taken on a new meaning. Scientists studying marmosets have discovered that over half the males carry their brother's sperm.

Marmosets, small monkeys that live in South America, have long been a genetic enigma. Marmoset mothers almost always give birth to fraternal twins, which develop from two eggs and are thus genetically distinct. In 1962, scientists at Dartmouth Medical School discovered that almost all marmosets carry some blood-generating stem cells that began in their twin sibling.

Animals that carry cells from another individual are known as chimeras. Aside from marmosets, chimeras have been discovered in humans, cats and cows. But scientists have long thought that chimerism was a rare fluke.

Marmosets were different. Almost all of them had chimeric blood, and they were all healthy. It appears that they swap cells so often because of their peculiar development. In the womb, their placentas grow quickly and fuse, creating a network of blood vessels through which cells can travel from one twin to the other.

In 1991, Jeffrey French, a primatologist at the University of Nebraska, Omaha, set up a colony of marmosets. He and his colleagues have tracked their family history ever since. Recently one of his graduate students, Corinna Ross, set out to find a paternity test for marmosets. She developed a method much like the test used to identify human fathers. Small regions of DNA known as microsatellites are very prone to mutating, creating a kind of genetic fingerprint that's different from one family to another.

"We were hoping that we could use hair for paternity analysis, but that's not quite how it worked out," Dr. Ross said. "The initial results were very odd."

Different hairs from the same marmoset had different genetic fingerprints. Some of it matched the DNA of the marmoset's twin.

Working with Dr. French and Guillermo Orti, a University of Nebraska geneticist, Dr. Ross then studied other tissues from marmosets. "We found chimerism throughout everything," she said.

The pattern was different from one marmoset to the next. "A single individual might be chimeric for hair and liver, for example, and not for anything else," Dr. Ross said.

One of the most surprising results of the study is that over half of male marmosets have chimeric sperm. Dr. Ross and her colleagues discovered cases in which the DNA of male marmosets turned up in babies supposedly fathered by their fraternal twins. In other words, the sperm came from one male, but it had the DNA of the male's brother. A paternity test would show that the baby's genetic father was actually its uncle. The scientists were not able to isolate DNA from marmoset eggs, but they did find that 2 out of 21 marmoset ovaries were chimeric. It's possible that a female marmoset can give birth to nephews and nieces.

The discovery of rampant chimerism in marmosets led the Nebraska scientists to wonder if it affected how parents treated their children. Primates can recognize their offspring by distinctive odors. But a marmoset with chimeric skin would give off two odors — its own, and that of its twin sibling.

The scientists found that mothers carried babies with chimeric skin less than they carried babies with only one set of skin cells. Fathers, on the other hand, carried chimeras over twice as much as non-chimeras.

Scientists have long noted that marmosets are unusual among primates for their doting fathers. Chimeras may be the source of their attention. It's possible, Dr. Ross suggests, that chimeras give off a wider range of odors that signify that they are related to a father, increasing his attention.

The results of the marmoset study appear this week in The Proceedings of the National Academy of Sciences.

"It's potentially a really interesting finding," said David Haig, an evolutionary biologist at Harvard. Dr. Haig is particularly intrigued by the genetic relatedness of chimeric twins. On average, two normal fraternal twins would share about half their genes. Marmoset twins are more closely related because they have more genes in common.

That common bond might drive the evolution of unusual kinds of behavior. Dr. Haig notes that in a band of marmosets, only the oldest female can reproduce, while the younger individuals help raise her offspring.

Dr. Ross, who now works at the South Texas Centers for Biology in Medicine, is continuing to study the marmosets to understand the effects of chimerism. The questions she hopes to answer are not just scientific, but philosophical.

"This changes how we think of marmosets as individuals, but it also changes how we think of the term at all," she said. A ma
le mates with a female, who gives birth to his brother's offspring. "But most of his body also has his brother's genes. So what is he as an individual?"

[Lucidor]

All human females have X chromosome chimeraism, i. e. one of the X chromosomes is randomly shut down early in the embryogenesis, with the descentant cells having the same X chromosome inactivated.

http://en.wikipedia.org/wiki/X-inactivation

[jimmy olsen]

All human females have X chromosome chimeraism, i. e. one of the X chromosomes is randomly shut down early in the embryogenesis, with the descentant cells having the same X chromosome inactivated.

http://en.wikipedia.org/wiki/X-inactivation

Why don't females exhibit recessive genetic diseases carried on the X chromosome like hemophilia then?

[The Brain]

Seems that the "scientists" in Nebraska haven't heard of the oldest trick in the book. "No you're wrong about me and your brother, honey! It's your sperm. It's chimeric!"

[Lucidor]

All human females have X chromosome chimeraism, i. e. one of the X chromosomes is randomly shut down early in the embryogenesis, with the descentant cells having the same X chromosome inactivated.

http://en.wikipedia.org/wiki/X-inactivation

Why don't females exhibit recessive genetic diseases carried on the X chromosome like hemophilia then?

Because most inherited recessive disorders are due to deletions (loss of a functioning gene), making those poor suckers with only one X chromosome more susceptible, i.e. the men are the ones that get X linked haemophilia.

[Ideologue]

All human females have X chromosome chimeraism, i. e. one of the X chromosomes is randomly shut down early in the embryogenesis, with the descentant cells having the same X chromosome inactivated.

http://en.wikipedia.org/wiki/X-inactivation

What would happen if, for example, the X chromosomes were identical?

[Fate]

All human females have X chromosome chimeraism, i. e. one of the X chromosomes is randomly shut down early in the embryogenesis, with the descentant cells having the same X chromosome inactivated.

http://en.wikipedia.org/wiki/X-inactivation

Why don't females exhibit recessive genetic diseases carried on the X chromosome like hemophilia then?

The transcription product from one functional chromosome is generally sufficient if a disease is X-linked recessive. For example Hemophilia A is caused by the lack of functioning clotting Factor VIII. It's not like the functionally inactive product is preventing the normal functional gene product from doing it's job. Now say if you have random X-inactivation that preferentially affects the good allele over the bad, which is statistically unlikely but possible, then a woman with one bad Factor VIII allele can exhibit milder forms of an X-linked disease like Hemophilia A.

[Fate]

All human females have X chromosome chimeraism, i. e. one of the X chromosomes is randomly shut down early in the embryogenesis, with the descentant cells having the same X chromosome inactivated.

http://en.wikipedia.org/wiki/X-inactivation

What would happen if, for example, the X chromosomes were identical?

I'm aware of nothing special that could happen. One of the two X chromosomes would be inactivated. The main purpose of X-inactivation is to prevent a cell from transcribing too much gene product. You don't need two X chromosome's worth of mRNA. That's why men (46, XY) are perfectly fine with just one. Women with pentad X syndrome (49, XXXXX) have one inactive X-chromosome and four active ones in each cell. It causes severe genetic deformities because the cell is out of balance in terms of what it's transcribing.

[Ideologue]

But if it were the case that one X-chromosome is all you need, one would expect that women who early on in development lose an X-chromosome in some of their cells (giving those cells a 45 X karyotype) to be fine, but instead they have Turner syndrome.  So the Barr body must have some function that I don't understand; or that the mosaicism that results in tissues having two different karyotypes sucks; or that the root cause of 45 X karyotype, a loss of the second X chromosome that sometimes doesn't get rid of the entire thing even in the affected cells, is problematic in itself but a clear wipe of the 46th chromosome would have lesser or even nonpathological effects.

Intuitively, I'd think that two identical X-chromosomes, one of which is deactivated, would be fine, though, sure.  My larger purpose was making a joke about my clone bride.

[Fate]

But if it were the case that one X-chromosome is all you need, one would expect that women with a single X-chromosome to be fine, but instead they have Turner syndrome.  So the Barr body must have some function that I don't understand.

Intuitively, I'd think that two identical X-chromosomes, one of which is deactivated, would be fine, though, sure.  My larger purpose was making a joke about my clone bride.

Barr bodies for the most part are transcriptionally inactive, but the pseudoautosomal region of the X chromosome escapes inactivation.  A woman needs the pseudoautosomal region on both X chromosomes to have the proper gene load. This is the reason for Turner's syndrome (45, X). The male Y chromosome has that same pseudoautosomal region thus both male and female will get a proper gene load.

But yeah, most people with Turner's syndrome are not truly 100% (45, X) which is highly lethal (I think something like 95% spontaneously abort). Turner's embryos that come to full term are in general genetic mosaics - a portion of their cells are (46, XX) and some are (45, X) or another variant karyotype.

[Ideologue]

Okay.  That makes sense.  Then an identical pseudoautosomal region would be fine.  Score.

So the only remaining question is bride... or back-up body?