Monday, February 18, 2013

Genes, Mothers And Lovers

The reality that mothers never completely leave behind ties to the fathers of their children is not just a social reality. It is a biological one.
Microchimerism is the persistent presence of a few genetically distinct cells in an organism. This was first noticed in humans many years ago when cells containing the male “Y” chromosome were found circulating in the blood of women after pregnancy. Since these cells are genetically male, they could not have been the women’s own, but most likely came from their babies during gestation.

In this new study, scientists observed that microchimeric cells are not only found circulating in the blood, they are also embedded in the brain. They examined the brains of deceased women for the presence of cells containing the male “Y” chromosome. They found such cells in more than 60 percent of the brains and in multiple brain regions. . .

Microchimerism most commonly results from the exchange of cells across the placenta during pregnancy, however there is also evidence that cells may be transferred from mother to infant through nursing.

In addition to exchange between mother and fetus, there may be exchange of cells between twins in utero, and there is also the possibility that cells from an older sibling residing in the mother may find their way back across the placenta to a younger sibling during the latter’s gestation.

Women may have microchimeric cells both from their mother as well as from their own pregnancies, and there is even evidence for competition between cells from grandmother and infant within the mother.
As John Hawks explains:
Mothers must suppress their immune responses to some extent during pregnancy, to avoid health risks to the developing embryo and fetus.
As a result, some of their children's DNA (even if the pregnancy does not end up giving rise to a live birth) ends up in their bodies for the rest of their lives. Some of a child's DNA comes from the father (the part that doesn't isn't distinguishable from the mother's DNA). Thus, most women carry genetic traces of the men who have impregnated them in their bodies for the rest of their lives.

A similar mechanism to microchimerism exchanges between older and younger siblings, involving testosterone impacts on women that influence younger siblings of male children has been suggested as one possible component of the biological basis of homosexuality.

These gene exchanges, by pregnant and nursing mothers with their children, and between siblings that have the same mother, as far as I know, are the only known non-viral mechanisms of horizontal gene exchange in modern human.

What does foreign DNA do in a woman's body?

The amounts of foreign DNA involved in these transfers is tiny.

No clinical effects of this gene transfer have been clearly established. But, impact of these gene exchanges may be positive, on balance, for the woman:
Since Alzheimer’s disease is more common in women who have had multiple pregnancies, they suspected that the number of fetal cells would be greater in women with AD compared to those who had no evidence for neurological disease. The results were precisely the opposite: there were fewer fetal-derived cells in women with Alzheimer’s.
There are also some experimental suggestions that microchimerism may have effects similar to stem cells in allowing a body to heal.

These transfers may play a role in generating stronger immune responses to cancer.

But, the immune effect could also be negative, for example, in aggravating autoimmune disorders like M.S., Type I diabetes, and lupus.

John Hawks hypothesizes that there may be other unknown downsides to this horizontal gene exchange for women, because if there wasn't, the amount of gene exchange that takes place would probably be greater.  It could be that the downside isn't to the gene exchange per se, however, but to the downside of having a suppressed immune system for a sustained period of time, which is what makes microchimerism possible.

Could this knowledge be used to intentionally treat diseases?

Pregnancy as a "golden hour" for microchimerism "vaccinations"?

To the extent that positive impacts are identified, one can imagine therapies, similar to gene therapies or vaccines, that inject foreign DNA with known characteristics into women during pregnancy or while they are nursing. 

In a more ethically challenging case, one could even imagine causing a woman, perhaps a woman with cancer or one who has been found to have very early stage Alzheimer's diesease, to become pregnant in order to theraputically induce foreign DNA with theraputic benefits into her system, and then terminating the pregnancy once that end was accomplished.

Improved immune suppression treatments

Alternately, one could better identify the biochemical processes that suppress the immune responses of pregnant women first.  This could facilitate organ transplants and stem cell-like horizonal microchimerism transfers of foreign DNA in both men and women, without actually causing the pregnancy of the patient.

Forensic applications

Limits on DNA testing accuracy in women

It is known that due to microchimerism it is possible (although extremely uncommon) for a tissue sample taken for a DNA test of a woman to capture foreign DNA in her body rather than her own DNA, and thus to produce inaccurate results.  The precise frequency with which this happens is unknown.  Genetic maternity tests are far less common than genetic paternity tests because a mother-child relationship is very rarely in doubt.  And, few people get DNA testing for other reasons because it has been extremely expensive until very recently. 

Of course, since errors related to microchimerism are generally still going to involve the DNA of a close relative, even a sample of foreign DNA within a woman may often lead to a DNA test result that shows a mother and someone else are related to each other, so it is possible in many cases to assume that a less than perfect DNA match that is still far too similar to be from an unrelated person is simply a statistical fluke.

Only a handful of cases of these kind of chimerism related DNA testing errors have been documented.  But, in the absence of organized systemic research with unbiased samples, one can only place weak lower bounds on how common of a problem this could be that are also hard to distinguish from other kinds of very rare but probably non-zero frequency experimental errors, like accidental mixups of tissue samples in laboratories, that are rarely quantified when DNA test accuracies are quoted by experts.

Ideally, DNA tests of women who have been pregnant should be based on tissue samples from more than one location in her body in order to virtually eliminate this risk of error in DNA tests of women who have been pregnant in the past.

Distinguishing clones

Some day in the not so distant future, there may be forensic reasons that we want to be able to distinguish an organisim who is a source for cloned cells (not necessarily human) from a cloned organism.

Assuming that the two are gestated in different mother's wombs, comparing microchimerism genes in the two organisms ought to reveal differing genetic traces of the gestational mothers of the two organisms which are identical in autosomal genetics to each other. This likewise might provide a means of distiniguishing two different clones with the same source organism but different gestational mothers from each other.

Parthenogenetic clones (i.e. virgin births known to take place in animals such as certain snakes and sharks), should lack distinguishable microchimerism since the gestational parent and clone source would be the same.

Most likely, this technology would be developed first in the context of cloned farm animals, rather than human clones, a procedure that is banned now, but is rumored to have taken place a small number of times.

Investigating murders of women where a history of incest is suspected

In principle, it ought to be possible for a very complete molecular level autopsy of cells from many locations in a deceased woman's body to reconstruct who all of the men who impregnated her in her life were and also to reconstruct some of the DNA of her mother that she did not inherit as part of the maternal genes that were part of the egg that was fertilized when she was conceived.

Usually, there are much easier ways to gather this information and it is hard to imagine an ancient DNA sample being so well preserved that this kind of information could be recovered from that source.

But, one could imagine this having practical implications in investigating a suspected case of incest-suicide or incest-homicide where pregnancies were terminated before term or a newborn child of the victim died with the body disposed of to hid evidence of the crime.

Related benefits of forensic epigenetic information: histories of abuse and drug addiction

A detailed molecular autopsy sufficient to identify microchimerism would also reveal a wealth of epigenetic data, some of which would have forensic applications.

Research unrelated to the studies of microchimerism discussed above have found that a history of abuse has been found to leave epigenetic traces that determine if a person's death was the produce of a history of abuse, as opposed to an isolated instance of violence at the hands of a stranger.  Alternately, epigenetic analysis of a criminal defendant claiming a history of abuse as a mitigating factor in a sentencing hearing might be able to use this information to defeat arguments that the criminal defendant was simply making up the history of abuse in an effort to win leniency.

Epigenetic data would often be able to reveal if an individual (either a criminal defendant or an autopsied body) was addicted to drugs.

No comments: