“Are the viruses’ friends or enemies or a bit of both ‘frenemies’ shaping our evolution”

By Prof Kuldip Sidhu, PhD, GdipBA

The current pandemic situation caused by Corona viruses seemingly make them our enemy number one though it may not be totally true from evolutionary perspectives.  About 100,000 years ago, human evolution faced a serious bottleneck: Our ancestors were reduced to perhaps five to ten thousand individuals living in Africa. These handful individuals in time, evolved into “behaviourally modern” humans, expanding dramatically in both number and range, and replacing all other co-existing evolutionary cousins, such as the Neanderthals. The cause of the bottleneck remains unsolved, with proposed answers ranging from gene mutations to cultural developments like language to climate-altering events, among them a massive volcanic eruption.

Add another possible factor: infectious diseases with microbes and viruses.

It may be unimaginable to fathom, but the human body is co-inhabited by large collections of microorganisms, commonly referred to as our ‘microbiome’, that have evolved with us since ages. It is estimated three are about at least 38 trillion bacteria.  But hang on, more intriguing, perhaps, is that bacteria are not the most abundant microbes on our bodies, the Oscar goes to viruses, there are about 380 trillion of them and referred to as human virome. But these viruses are not the dangerous ones you commonly hear about, like those that cause the flu or the common cold, but more sinister infections like COVID, Ebola or dengue. Many of these viruses instead attack the bacteria that reside and are known as bacteriophages, or phages for short and protect us. In essence there are more microbes and viruses in our body than our own cells about 20 trillion.

If the human body is studded by so many microbes and viruses – what could be the scientific relevance or purpose? Let us try to dissect out this intriguing question a bit more objectively

Human Molecular Evolution

The modern looking human beings are not just the apparent physical transformation of our ancestors, the Neanderthals, but instead the outcome of very intricate changes at the molecular levels in your DNA called the ‘molecular evolution’ and these microbes and viruses are playing a crucial role towards creating super human beings.

Viruses are considered non-living, evolved much earlier than us and are simply a string of genes (RNA or DNA molecule) rapped in a protein coat (capsid). Principally they all work in the same basic way. Their co-existence with humans is the outcome of their million years of co-molecular evolution with us. Binding of virus to our cells is a molecular event similar to sperm binding to an egg during fertilisation, both involve  using specific surface antigens on their body that allow binding to a receptor like a lock and key mechanism (like spike protein in CORONA virus binding to ACE2 receptor in lungs). It’s not a random event but an outcome of a million years of co-molecular evolution of hosts and viruses.

Once the cell is infected by a viral particle (DNA/RNA, Capsid), and goes inside the cell, it virtually hijacks the cell’s own molecular machinery to copy its genes and start manufacturing its own viral proteins and particles (replication), millions of these particles are created this way and eventually burst out  in search of new host to attack again.

For most flu viruses, the story ends there. But a handful of more serious retroviruses – including HIV, Simplex viruses (cold sour, Shingles), Corona viruses they are found to be much more sneakier, smarter and once inside the cell, they start smuggling their genetic materials  into our DNA. They insert themselves randomly into the genome of an organism, lying low until the time is right to start viral production again. These are the viruses shaping our evolution for ages.

It is considered that about 50-80% of the human genome is studded with millions of DNA sequences that can be traced back to long-dead viruses collectively known as transposable elements or ‘transposons’. For many years, these large chunks of repetitive virus-derived DNA littering the human genome were dismissed as ‘junk DNA’. But with modern molecular tools scientists have found out that these transposons and junk DNA have been preforming crucial role as drivers (our slaves) of our molecular evolution. Some of these transposons become our molecular switches controlling our genome expression. Sometimes, random mutations in these switches can turn them on or off and thus become the hallmark of some of the diseases like cancer, Alzheimer’s etc. In my previous articles on viruses I eluded to many of such magic feats they have been preforming over ages and will elaborate a bit more with examples here.  

Evolution of placenta reproduction in higher mammals

The basic principle of evolution is to accumulate useful variations (mutations) and their inheritance that eventually give the species a better chance to compete, survive and thrive (Darwin’s theory of evolution by natural selection – survival of the fittest with key elements; variation, reproduction, and heritability). Placental reproduction in higher mammals like humans gave them a better chance for foetal survival. For comparison, in lower mammals like metatherian, marsupials- kangaroos – reproduction is very inefficient – lack of placenta in them leads to foetal loss quite frequently.

Very recently it was discovered that a set of two genes responsible for forming placenta in higher mammals known as ‘syncytin’ bears a close resemblance to a retrovirus probably acquired during the molecular evolution. Syncytin causes fusion of multiple cells as a sheet that forms the placenta and latter gives better protection to foetus and also protects foetus again mother’s immune system.   These syncytin genes are similar in human and primates but do not resemble with those in other species indicating that different retroviruses played role in their molecular evolution. Clearly, all these mammalian species were infected by particular viruses millions of years ago and over time, those viruses have been harnessed to play a key role in placental growth, making them a permanent fixture in our genome and gave an edge in our evolution.

Evolution of placental reproduction in humans and the role of viral syncytin gene in formation of syncytium (sheet of cells-placenta).

To be continued…