30 million years ago, a mega-plague ravaged the world, and it lasted for 15 million years, and as a result, we humans today carry this virus in their DNA? And not only in the primate order of human beings, but also on rodents, carnivores to a greater or lesser extent to this day.
Why are they called ERVs? How did the ERV virus wreak havoc around the world, and why did it become almost indiscriminate? How did it stop when it was so infectious? Is it still latent in our DNA, does it do any harm to humans? Let's sort it out slowly.
How did we find the virus 30 million years ago?
We can start by defining plague, which can be caused by bacteria or viruses. The plague caused by the bacteria we are more familiar with is the plague, which is spread by Yersinia pestis through flea bites. Plagues caused by viruses, such as influenza viruses, can be called influenza plagues, which are more likely to cause pandemics than bacteria.
Looking at it this way, the main culprit of the global pandemic 30 million years ago is that the virus has not escaped. Viruses are tiny parasites that depend on host cells for replication and propagation. There are many types of viruses, some can cause various diseases in humans or animals, and some can coexist harmoniously with the host and even benefit the host.
Since it was a plague that was circulating 30 million years ago, how did we find it? In fact, humans found it in their own DNA and in the DNA of other animals. They are called ERVs.
They are formed by retroviruses infecting the germ cells of human ancestors and integrating their own genes into the host's DNA. These viral genes are passed on from generation to generation as the host is inherited, becoming part of the human genome. According to research, about 8% of the sequences in the human genome are composed of ERVs, and some of them still retain certain transcription and expression capabilities, which have an important impact on human physiological functions and disease occurrence.
Among all ERVs, there is one type of ERV that has attracted special attention from scientists, and they are called ERV-Fc, which is a member of the γ-retrovirus family and is most closely related to the current mouse leukemia virus and feline leukemia virus. ERV-Fc is an integration of γ-retroviruses that have been continuously infected with eumammals between 30 million and 15 million years, and they are widely found in the genome of eumatrics, including humans.
In primates, especially humans, there are two segments of ERV-Fc, one on the X chromosome and one on chromosome 7, representing two γ-retroviral integration events. So why did this virus infect so many species almost indiscriminately, how did it wreak havoc around the world, and what harm did ERV-Fc do to animals at the time?
The Great Plague of Indiscriminate Infection 30 million years ago
According to scientists' research, ERV-Fc is a virus that can be transmitted across species, and it can infect different mammals through blood, body fluids, semen or saliva, including primates, rodents, carnivores, dairy cows, horses, etc.
It was active from about 30 million to 15 million years ago and covered all continents except Australia and Antarctica. This period, which belongs to the late Pleistocene, experienced alternating glacial and interglacial periods, which led to fluctuations in temperature and sea level. This makes some species less able to adapt to the environment, which eventually leads to their extinction.
Large-scale volcanic activity also occurred frequently during this period. Volcanic eruptions release large amounts of gas and ash that have a short-term impact on the global climate. The melting and refreezing of glaciers has led to fluctuations in sea levels, affecting coastal and aquatic ecosystems. Organisms face the challenge of habitat loss and food chain disruption.
During this period, some mammals gradually emerged, such as early herbivorous mammals, rhinoceros, elephants, primates, rodents, etc. This is when ERV-Fc emerged and indiscriminately infected these mammals. But these infections have also had a profound impact on the evolution and adaptation of these species.
ERV-Fc infection can cause damage and alteration of the host genome at that time, resulting in mutations, recombinations, deletions, or insertions of genes. These changes will affect the physiological functions of the host, such as the immune system, reproductive system, nervous system, etc., thus causing different degrees of pathological effects, such as immunodeficiency, infertility, cancer, neurodegenerative diseases, etc.
On the other hand, these changes also provide the host with some favorable characteristics, such as antiviral, antiparasitic, antioxidant, anti-aging, etc., which enhance the host's adaptability and survival advantage. ERV-Fc infection can be seen as a double-edged sword, with both advantages and disadvantages, and has important implications for host evolution and survival.
In rodents, ERV-Fc infection leads to the recombination and deletion of some genes, such as in mice, the integration of ERV-Fc leads to the deletion of some genes, such as Mx1, Mx2, Oas1, etc., these genes are related to the ability to resist viruses, therefore, mice are more sensitive to the infection of some viruses, such as influenza virus, dengue virus, etc.
For hamsters, the integration of ERV-Fc leads to the recombination of some genes, such as on the X chromosome of hamsters, the integration of ERV-Fc leads to the recombination of a section of genes, forming a new gene called Sxlf, which is related to the sex determination of hamsters and can cause male hamsters to produce female reproductive organs, resulting in male sterility.
In felines, the integration of ERV-Fc has led to the insertion of some genes, such as on chromosome 7 in cats, the integration of ERV-Fc has led to the insertion of a gene called RD114, which is associated with leukemia virus infection in cats and can act as a receptor for the virus, thereby increasing the risk of infection in cats. In canids, the expression of ERV-Fc is related to the regulation of the dog's immune system and can be used as an immunomodulator, thereby enhancing the dog's immunity.
Although it is a double-edged sword, there are still people who worry that this virus is playing a role in our NDA, so is it still a threat to us?
There is a lot of "garbage" in human DNA?
In fact, ERV-Fc is not as terrifying as imagined for humans, first of all, it is not a coding gene fragment, but a non-coding gene fragment, and the non-coding fragment has little impact on humans, and the HERV-Fc1 and HERV-Fc2 in our genes are involved in the regulation of human embryonic development and pluripotent cells, which is equivalent to saying that it has become a part of our body.
Some people say that most of our DNA is garbage, because not all DNA fragments are genes, and in short, not all DNA fragments can code for proteins. Only 1.5% of our DNA is genetic, and only that 1.5% of DNA fragments can code for proteins.
What we've been saying about ERV-Fc in the human gene is that 98.5% of the non-coding sequences, that is, they don't directly code for proteins, so what are the remaining 98.5% of the DNA fragments used for? Are they functional? Are they garbage?
This question is actually quite complicated, because in addition to genes, there are many other types of DNA fragments in human DNA, and their functions and roles are different.
Some have been discovered and studied by scientists, while others have yet to be revealed. Some of these non-coding DNA fragments are beneficial to the human body, some are neutral, some are harmful, some are remnants of evolution, and some are raw materials for evolution. We can't just call them all garbage, and we can't just think that they're all useful.
We think of DNA as a guide to how our bodies work. In this guide, there are special chapters that are not the main point, but which cannot be missing. One of the chapters is called "Regulatory Sequences". These sequences are special pieces of DNA that, while not directly encoding proteins, are able to influence the process of protein production.
These regulatory sequences are like "controllers" of genes, and there are buttons on this controller, including promoters, enhancers, silencers, terminators, etc. They can interact with other proteins, such as transcription factors, like a complex switch system that controls the switch, intensity, timing, and location of genes.
For example, we all know that our blood type is genetically determined, but the expression of this gene is regulated by a special "enhancer". If there is a change in this enhancer, it can lead to problems with gene expression and eventually some rare blood types, such as the Bombay rare blood type.
At the end of the chapter on regulatory sequences, let's talk about the chapter "Jumping Genes", which are also called motile genetic factors. Figuratively speaking, they can "jump" in the genome at will, jumping from one place to another.
They are also not involved in coding, but they have their own special skills, being able to transcribe (copy themselves) and copy (paste elsewhere), and they are not dependent on the host genome and can exist independently. More than half of the members of the human genome are made up of these skipping genes.
The "jumping" behavior of these motile genes is no joke, and sometimes their activity can bring some confusion to the genome. This includes mutations, recombinations, deletions, or insertions of genes into new locations. These changes may have an impact on the host's body, causing diseases such as immune system deficiencies, infertility, cancer, and neurodegenerative diseases.
But there is another side to these "jumps", and their changes may sometimes also bring benefits to the host, such as enhanced resistance to viruses, immunity to parasites, and even favorable characteristics such as antioxidant and anti-aging, improving the host's adaptability and survival competitiveness.
There are many non-coding DNA fragments in our DNA, and I can't say too much about them, such as pseudogenes and repetitive sequences, all of which have more or less influence on us. It's like a double-edged sword, which can bring both benefits and problems.
While only 1.5% of the human genome encodes proteins, the remaining 98.5% of non-coding sequences contain many elements that are essential for the development, function, and fitness of organisms. The function of these non-coding sequences is still being studied and understood. So we can't simply call them "garbage".
epilogue
Through genes, scientists have discovered a super-plague that has ravaged for 15 million years, and the effects of this plague still leave traces in our DNA today. Between 30 million and 15 million years, they infected a wide range of mammals, including humans, and became part of our genome.
Although only 1.5% of our DNA encodes proteins, the remaining 98.5% of non-coding sequences also carry important functions. These sequences include regulatory sequences, motile genetic factors, etc., which not only affect the transcription and expression of genes, but also participate in the stability and functional regulation of the genome.
Some people call this part of the non-coding sequence "garbage", but in fact they all have their own roles!
Resources
ERV-Fc;Wikipedia
ERV: 内源性逆转录病毒；Endogenous Retrovirus
A brief discussion on the comparison between coding sequences and non-coding sequences, Liu Botan, 2023
Specific regulatory mechanisms and functions of different subfamilies of ERV in early human embryos;Hongqing Liang/Dan Zhang, 2022
Mainland scientists have found that blocking endogenous retroviral reactivation and transmission can alleviate organism aging;BioValley, 2023
Using the Genome of Modern Mammals to Trace the Interspecific Transmission and Long-Term Evolution of Ancient Retroviruses; William Deere, 2016