How viral symbiosis works
Yes -- I have written about it in less scientific detail on pseudoscience, but have been encouraged to make it more scientific here.
WHY WE DON'T LAY EGGS
Among the many animals that live on land, and in the oceans, only the mammals don’t lay eggs. They protect the developing foetus within the mother’s womb for lengthy periods, so that it is born into the world as a fully formed baby. To achieve this, mammals have evolved a very special organ capable of nourishing the foetus in the womb, and all the while protecting it from being attacked by the mother’s powerful immune system. The organ that makes this possible is the placenta. We humans have the most specialised placenta of all the mammals, more deeply penetrating into the mother’s womb, and with an exquisitely fine membrane, only a single cell thick – much finer than tissue paper – that separates the mother’s blood from that of the foetus, and through which this all-important nourishment takes place. This ultra fine membrane is very unusual – its cells are fused together so their membrane have dissolved away, making up a single monolayer. Animal genes cannot fuse cells in this way. How then does our human placenta, vital to every human birth, manage to do this?
It does so with the help of very special types of viruses, which have been incorporated into our chromosomes. The discovery of these viruses has shocked the world of science, since scientists are more familiar with viruses as the cause of infectious diseases, such as AIDS and flu. But now we know that these viruses really are playing a key beneficial role in our human life story. They are known as human endogenous retroviruses – in the scientific jargon, HERVs – and they have, in essence, become an integral part of us through an evolutionary mechanism known as genetic symbiosis. More remarkably still, these viruses have a genetic make-up that is very similar to the virus HIV-1, notorious as the cause of AIDS.
What you are looking at in the ERVWE1 locus is the genetic locus, on chromosome 7, that codes for syncytin-1, one of the viral proteins that fuses the placental cells into a syncytium, which in turn is vital for normal human placental function to take place.
If you examine just the right hand side of the upper portion of the figure, between the two narrow vertical red bands, you will find that you are looking at the genome of a human endogenous retrovirus, labelled ERVWE1 (a human endogenous retrovirus of the HERV-W family), which has a very similar basic genomic structure to HIV-1, the virus that causes AIDS. The viral genes (labelled Agag, Apro-pol, and env – the latter coloured yellow) are the same genes (more correctly genetic domains, since they code for multiple functions) that you find in HIV-1, and the env gene is the genetic domain that codes for the surface envelope structures of the retrovirus. So syncytin-1 is the expressed protein product of the viral env gene. It could hardly be called a “captured” viral gene, since it remains an integral part of the viral genome, and it is promoted and further regulated by the viral 5’ LTR (regulatory dynamo known as a long terminal repeat) and the 5’ LTR of a second pair of flanking LTRs derived from a second human endogenous retrovirus, known as MaLR (these are coloured red). There are many other reasons why we should avoid regarding viral sequences as captured or the equivalent of vertebrate-derived genes, which we may come to later.
The question, then, is how has the human placenta acquired the ability to express a retroviral gene, within a viral structure, promoted and regulated by viral LTRs as part of its essential make-up?
People familiar with symbiogenesis – symbiosis as an evolutionary force – will also be familiar with a level of symbiogenesis known as genetic symbiogenesis. I propose that what we are looking at here is the symbiogenetic union of a viral genome with that of its vertebrate host – we humans.
In genetic symbiosis, we would expect that selection will work at the level of the combined genomes. Viral genes mutate very rapidly. For a virus to be not only expressed in every human pregnancy, but also for its env gene (and regulatory sequences) to be conserved over vast time periods (see figure 2, the next stage of the figure), it must have been conserved by selection as an integral part of the combined virus-vertebrate genomic union – what in symbiological terms would be terms the “holobiontic genome”.
Thus I would suggest that, just considering this single example, it demonstrates that viral symbiosis is real and important in human evolution. Viral symbiosis is clearly very different from mutations, in their original definition, of random changes in genes arising from copying errors during cell division. The genes involved here, indeed the whole viral structure working as a unit, is pre-evolved from a very different evolutionary lineage to that of its host. Moreover, it is also pre-evolved to take over and manipulate key aspects of host genetic function, which it does as part of normal infectious and replication strategies. This latter lends such viruses very considerable symbiogenetic potential when they unite, genome-for-genome, with the germline of their hosts.
Of course the human endogenous retroviruses story does not stop there. We now know of eight separate viruses that play an important role in placentation. And vast numbers of viruses, from roughly 200 different viral evolutionary lineages, are scattered throughout our chromosomes. The evidence that those viruses are not junk has been accumulating for something like twenty years. A Swedish pathologist, Erik Larsson, has recently discovered that the syncytins are also playing some important, but as yet unknown, function in the normal human brain. Others are showing more and more roles for HERVs in human embryology, and our day-to-day physiology. Indeed, this viral part of our makeup is becoming very important to our understanding of human diseases.
For example, in multiple sclerosis, a slightly different form of syncytin-1 may be playing an important role in the inflammation that damages the insulation sheath around the nerve cells, known as myelin. Other studies, by doctors in Italy, have shown that our human viruses are playing a very important role in seven or eight of the common forms of cancer.
I am in the process of publishing a series of 5 review papers for the Journal of the Royal Society of Medicine, extrapolating this knowledge into medicine. The first three are now published, with four and five appearing in November and December.
I shall stop here at this early stage to allow people to question, comment, debate, or disagree with me.
