The human genome is the complete set of instructions for building and operating a person. This vast library of deoxyribonucleic acid (DNA) contains the code that defines our species and determines our individual traits. However, this biological text is not exclusively composed of self-originated sequences.
The long history of life includes countless interactions with infectious agents, some of which have left permanent marks on our hereditary material. These foreign genetic components have become integrated and passed down through generations. The presence of these sequences within our chromosomes raises questions about the boundary between self and non-self at the most basic biological level.
The Viral Percentage in Human DNA
Approximately eight percent of the human genome is estimated to be composed of sequences derived from ancient viruses. This represents a massive contribution of foreign genetic material that is now a stable, inherited part of our DNA.
To put this figure into perspective, the DNA sequences that code for proteins make up only about one to two percent of the genome. The viral remnants, therefore, occupy a significantly larger portion of our genetic code than the genes responsible for all known human proteins. This inherited material is distinct from the genetic code of viruses acquired through recent or active infections, which are not passed down to offspring.
Defining Endogenous Retroviruses
The viral sequences that account for this large percentage are known as Endogenous Retroviruses (ERVs). These are the genomic fossils of retroviruses, a class that includes modern-day HIV, which inserts its genetic material into the host cell’s DNA. This integration process is what makes these sequences “endogenous,” meaning they originate from within the host genome itself.
For a viral sequence to become endogenous, the initial infection must have occurred in a germline cell, such as an egg or sperm cell, or one of its precursors. When this happens, the viral DNA, now called a provirus, is passed down vertically from parent to child just like any other gene. Over millions of years, these ancient infections have accumulated, and their genetic remnants have become fixed in the human lineage.
Most ERVs found today are fragmented and have lost the ability to produce active, infectious virus particles due to millions of years of accumulating mutations. A complete provirus typically contains genes like gag, pol, and env, flanked by regulatory sequences known as Long Terminal Repeats (LTRs). Many ERVs have degraded into just these LTRs or small, non-functional gene fragments.
The Evolutionary Role of Integrated Viral DNA
While the vast majority of ERVs are inert relics, some sequences have been repurposed by the host genome over evolutionary time. This process, called co-option or domestication, involves the host using the viral genetic instructions for its own benefit. The most striking example is the role of ERVs in the formation of the placenta in mammals.
Specific ERV env genes, which originally coded for the viral envelope protein, were co-opted to create proteins called syncytins. Syncytin-1 and Syncytin-2 are necessary for placental development. They promote the cell-cell fusion of placental cells (trophoblasts) to form a continuous, multinucleated layer called the syncytiotrophoblast, which facilitates nutrient and gas exchange between the mother and the fetus.
Beyond these specific protein-coding functions, the LTRs of ERVs can also act as regulatory elements for nearby human genes. These LTR sequences contain elements that act as promoters or enhancers, altering when and where a gene is turned on. This influence on the expression of surrounding human genes contributes to genetic diversity and shapes gene regulation.
Mapping and Distinguishing Viral Sequences
Scientists use genomic sequencing and advanced computational tools to identify and quantify these ancient viral fragments. The process relies on recognizing specific structural features characteristic of retroviral integration events. For example, the presence of LTR sequences flanking the remnants of the viral genes is a strong signature of an ERV.
Bioinformatics tools, such as RepeatMasker, scan the entire human genome sequence to identify these repetitive elements and their characteristic structures. Researchers also employ specialized software like ERVmap to analyze sequencing data and map the precise location of these insertions. Distinguishing ERVs from other non-viral repetitive DNA is an ongoing challenge, but unique sequence homology to known retroviruses aids classification.
Specific genomic markers, such as DNA methylation patterns and certain histone modifications, help researchers identify these sequences. These markers indicate that the host cell has chemically silenced the ERV DNA to prevent its expression, which is a common state for these ancient proviruses. Precise measurement is complicated by the fragmented nature of many ERVs and the subtle sequence divergence between them.