Like a Virgin (18 page)

The last common ancestor of mammals, birds, and reptiles is likely to have had only the chorion, the outermost of a true placenta’s four layers, and a very basic one at that. Today, you
can see a chorion when you peel a hard-boiled egg; it is the delicate layer that you find sticking to the shell, just inside. In modern birds and most reptiles, this thin, translucent membrane
allows gases to be exchanged between the egg and the outside air. Our last common ancestor would also have had a yolk sac, which in modern birds, reptiles, marsupials, and some fish circulates
nutrients to the developing embryo; it would also have had a primitive allantois, another sac-like tissue that gives rise to the blood vessels of the mammalian placenta as well as the umbilical
cord. In chickens, the chorion and part of the allantois fuse together, forming a layer thick with blood vessels that pulls calcium from the eggshell to help nourish the embryo. In most marsupials,
the allantois develops no blood vessels, since the embryo remains in the pseudo-placenta for only four or five weeks; instead it serves to store waste from the foetus’s kidneys, a critical
job ensuring that the embryo doesn’t abort from toxicity. In other mammals, though, the allantois serves this purpose but is wound up in the wiring of the umbilical cord. Somehow it is these
basic layers, the chorion and the allantois, that in mammals became the complex placenta.

Early in human development, after sperm meets egg and the DNA from father and mother have fused, the fertilized egg divides into two cells, as we saw in the last chapter. But the story is not as
simple as that: the two cells are not equal. One of
the cells is larger, and will continually and rapidly outgrow the other, as it divides over and over again. As the larger
cell masses into a solid ball, it is surrounded by a flattened ring of tissue, constructed through the labour of the smaller, more slowly dividing cell. In nine months, it is the solid ball of
cells that will be pulled screaming from the womb as a newborn child. The outer ring, called the
trophoblast
, will never become a part of the baby. It is the precursor of the placenta.

As the trophoblast grows into the life-support system for the embryo, in humans it will twice invade and destroy the lining of the mother’s womb. The first time happens within a week of
conception. Fifteen weeks after conception, the second incursion occurs. This time the cells penetrate far deeper into the uterus, boring one-third of the way into the womb’s walls and
entwining itself there in a structure that resembles a labyrinth, ensuring that nutrients can be leached from the mother in order to feed the foetus. A cycle of creation and destruction appears
even here.

In primates, including humans, biologists believe that, over evolutionary time, the trophoblast gradually infiltrated the mother’s womb more and more deeply as the size of the foetal brain
grows larger and larger. The brain, for instance, needs about sixty percent of the total nutrition supplied to a human foetus, compared with about twenty percent in non-primate mammal embryos. This
may be why the human trophoblast invades the womb twice – something not seen in any other mammal.

The human placenta’s progressive and deep invasion into the womb poses a considerable challenge to the mother’s body. The mother’s immune system should protect her from
infections and other foreign threats. But when she is pregnant, her immune system is forced to tolerate certain foreign material – the embryo and the placenta, both of which grow from that
first cell that is half derived from the father’s DNA. From the
body’s point of view, these growths are parasites, sucking life from the mother’s body for
their own existence. Detection by the immune system of such foreign tissue would usually lead to organ rejection, and preventing rejection is a necessity when it comes to making babies.

To ensure their survival, the embryo and the placenta cannot simply suppress the mother’s immune system, as this would expose her (and her developing foetus) to the risk of infection
– even possibly death. Instead, the trophoblast produces a special subset of MHC class I molecules that protect the foetus from natural killer cells in the mother’s womb. These
particular molecules work only in the vicinity of the placenta – a neat biological trick. Still, these molecules are not all-important. If you were to destroy them, a mother would not
immediately reject her foetus or its placenta. How could that be?

There must be at least one other strategy that prevents full-blown immunological warfare between mother and child. As it happens, the genetic compromise does not seem to have been developed
specifically to adapt to life with a placenta. Instead, it depends on the fact that there is another, completely different source of DNA in the body. The cells that give rise to the placenta, and
which protect the inner layer of cells destined to become the baby from attack by the mother’s immune system, are unique: not only do they exclusively come from the father, some of those
genes are not even human. They are the DNA of ancient viruses.

Among egg-laying animals, which do not have placentas, contact between mother and foetus is very limited, of course. It is the shell that shields the embryo from the mother, and
the
mother from the embryo, and the shell is created entirely by contributions from the mother. The egg also does not stay inside the mother’s body for very long after
it is fertilized. Incubating a fertilized egg inside the mother’s body required an ingenious ploy. In 1997, Luis Villarreal, a molecular biologist at the University of California, Irvine,
wrote an article entitled ‘On Viruses, Sex, and Motherhood’ in which he recounted his theory of a very clever leap in evolution. In this article, published in the
Journal of
Virology
, he proposed that viral DNA played an essential role in the evolution of mammalian pregnancy.

Viruses are among the oldest and most successful life forms on the planet, and Villarreal and others believe that the virus in question would have infected a distant ancestor in our primate
lineage as far back as twenty-five million to forty million years ago. When you look at the genome of vertebrates, you find thousands of foreign elements that look a lot like the genetic
information harboured in retroviruses, a form of virus that creates DNA out of RNA (opposite to most viruses, which make RNA out of DNA) and integrates this new DNA into its host. Indeed, nearly
ten percent of human DNA today appears to be made up of old retroviruses. The most well-known retrovirus is HIV, the cause of AIDS, which shuts down the immune system, but other retroviruses have
been linked to tumour cell growth.

Deploying some of the same tactics that viruses use to evade our immune system, the viral DNA in mammals allowed another invader into the body: the foetus. These genes, known as
syncytin
genes, allow the body to protect, nourish, and incubate the foetus, giving it time to mature without the threat of rejection by the ‘host’ immune system. Without viral DNA, humans and
many other mammals might still be laying eggs. And
syncytin
genes are targeted on making the placenta, specifically at the level of the trophoblast ring of cells – exactly where
exchanges between the foetus and the mother take place. Importantly,
syncytin
genes instruct cells to fuse with each other. That is, they are able to force cells from
the lining of the mother’s womb, comprised solely of the mother’s DNA, to fuse with cells from the trophoblast, which is designed by DNA from the father alone.

It is important to note that
syncytin
genes work as diplomats rather than combatants in the war between different DNA: they do not affect the embryo’s development or the actions of
the immune cells; instead, they temporarily cloak the embryo, keeping it from being recognized and destroyed by the mother’s immune system. When a particular
syncytin
gene,
syncytin-A
, is disabled in mice, the entire architecture of the trophoblast changes dramatically. Embryos begin to grow, but at a slow rate, and fewer blood vessels form to feed them. The
pregnancies invariably end in miscarriage. A faulty placenta does not make for a healthy pregnancy, and this is exactly what the scientists attempting to create fatherless mice were fighting. Their
early experiments kept showing that when they tried to produce offspring with DNA originating only from sperm, the embryo struggled to develop; when they did the same with DNA only from eggs, the
embryos developed normally but the placenta and other supporting tissues failed to thrive.

But this raises a more perplexing question. Why would a father’s genetic contribution be necessary in making a placenta, when viral DNA appears in the genome of both sexes? Why
didn’t evolution give females the capacity to make a placenta all on their own?

The evolution of the placenta must have been something of a double-edged sword for our ancestors. While being able to
gestate inside an adult afforded
unprecedented protection for vulnerable young, mammalian embryos functioned like a parasite on the mother. Apart from the challenges to the mother’s immune system, the embryo drained
nutrients via the newly designed placenta. This nutrient flow has to be regulated by the body, so that neither mother nor embryo is starved. Ancient viral DNA cannot handle this; new genes with new
instructions had to tackle the task.

Not all genes in our cells work all of the time or in all parts of our bodies. Some, for instance, only work in the limbs when a foetus is developing in the womb; some only in the brain of an
adult. As this indicates, genes have to be turned ‘on’ to have an effect, a phenomenon known as
gene expression
. Gene expression can be understood as the process by which the
letters of the DNA code are ‘read’ and start the production of certain proteins, which tell cells (and thus everything in the organism) what to do and when to do it. For some parts of
the genome in animals, the expression of a particular gene is determined by whether it was inherited from the mother or the father.

As the placenta gradually evolved in mammals, evolution had to find a way to tell the viral genes and the newer genes when to start working and when to stop. Sometime around a hundred and
forty-eight million years ago, certain genes vital for the healthy development of the placenta started to become locked and unusable – coded so that they could never be read, or expressed,
since they sometimes mucked up the works. So even though the mother’s genome still contains all the genes it takes to grow a complete baby from one of her eggs, only some of them are allowed
to function. The same is true for some of the father’s genes. This sexual selection in whether a certain gene can be expressed is called
genomic imprinting
.

There is nothing inherently ‘wrong’ in the coding of these genes that don’t work. Imprinting doesn’t involve a mutation
or a mistake that stops the
gene from working – think of it as a padlock that means the gene’s DNA cannot be accessed. But just as a door can be opened if you find the right key, imprinted genes can be unlocked,
even erased, by different conditions. The process is by no means static. And of the twenty-three thousand human genes that can be expressed by making proteins, only about eighty are ever silenced
by imprinting. What is interesting is that many of these genes that are imprinted dictate not what we will look like, but are able to manipulate the growth and nutrition of the foetus in the womb.
It seems that when evolution invented sex, it used imprinting as a way of ensuring that the female needed the male to reproduce. The health and survival of any offspring depends heavily on the
father’s genes for making the placenta, since the mother’s genes have been locked. It seems that sperm do more than just deliver packets of DNA into eggs – they regulate pregnancy
itself.

Imprinted genes, like viral DNA, are a frontline in a battle: two beings fighting over scarce resources, with some genes trying to ensure the best result for the child at the expense of the
mother, and others, for the mother at the expense of the child. The majority of genes that are locked in the mother’s DNA but not in the father’s directly influence how many nutrients a
foetus is able to extract from the mother’s body. A father’s genes benefit if his offspring are larger and stronger when they are born, because that gives them a better chance of
surviving to adulthood and the father’s genes being passed on further – for the father, there’s no personal risk involved. In contrast, many of the mother’s genes that do
work at this stage are trying to curb the foetus’s growth – to keep those nutrients for the mother. Consider, too, that if every time she became pregnant, the mother could restrict
foetal growth, she would secure a better chance of producing more children from limited resources, and she would be less likely to die from complications of
childbirth.
Evolutionarily speaking, this is to the advantage of her genes, which would have more opportunities to be passed on to a future generation.