https://www.faraday.cam.ac.uk/about/people/dr-graeme-finlay/
Retroviral Solo LTRs (solo Long Terminal Repeats)
are they original, or acquired? Copyleft (freely shareable) Barry Desborough, 2026
A brief introduction.
This article assumes some familiarity with the subjects of genetics, retroviruses and endogenous retroviruses (ERVs). If you are not familiar with these topics, please continue reading this introduction. Otherwise you can skip it and go straight to “Are these doubts reasonable ones?”.
Retroviruses replicate by integrating their genomes with the DNA of host organisms whose cells are then induced to read (transcribe) the viral DNA back and create new copies of the virus. The integrated genomes are flanked by a pair of long terminal repeat sequences (LTRs) to create the -LTR--VIRAL GENOME--LTR- structure, called a provirus. LTRs contain promoter and regulatory elements that enable and direct transcription of the viral DNA by the host cell machinery.
Cell repair functions can reduce a -LTR--VIRAL_DNA--LTR- integration to a single solo -LTR-, losing the rest.
Viruses may integrate their genomes with the DNA of a host gamete, where they become heritable. These integrations are called endogenous retroviruses (ERVs). The integration process is called endogenization. Finding them in vast numbers in corresponding loci in different species establishes, beyond reasonable doubt, that the species share common ancestors that first acquired each ERV, as the integration process cannot target specific DNA loci. Only inheritance can explain the correspondences.
So only unreasonable doubts remain, one of which is the claim that solo LTRs are not necessarily of viral origin, as there is no viral DNA enclosed within an LTR pair. This article explains why it is an unreasonable claim.
I recommend, if you need to study more of the background, that you go to the Wikipedia entry on endogenous retroviruses, https://en.wikipedia.org/wiki/Endogenous_retrovirus or find alternative sources before continuing.
My own general FAQ on endogenous retroviruses is @ The ERV FAQ - Endogenous RetroViruses
Are these doubts reasonable ones?
Skeptics would question the evidence from ERVs for common ancestry among different types of creatures, notably common ancestry between humans and chimps.
Some skeptics claim that because endogenous solo LTRs do not include any viral genetic material, they can be questioned as having originated from viral integrations, and it is possible that they are features of some original genome.
For example, from https://www.patreon.com/posts/are-endogenous-146557842* - D Budinsky of "Standing for Truth Ministry”, Dec 24, 2025, claims,
“These solo LTRs lack gag, pol, and env—not because they are “broken fossils,” but because their function does not require viral replication."
Budinsky describes this as being “crucial”.
He also claims that as solo LTRs are genetically fixed in the population, they are also possibly features of original genomes.
This article addresses the specific claim that solo LTRs are not derived from retroviral integrations, and evaluates that claim using genomic structure and known DNA repair mechanisms. I shall proceed by explaining that the genomic structure of solo LTRs is consistent with recombination-derived remnants of proviruses, and show that they are not all fixed in populations.
For brevity, I refer to solo LTRs as “solos”, and non-solo, double-LTR proviruses and ERVs as “doubles”.
A schematic of relevant DNA sequences
*“Target site” is a bit of an unfortunate name for where the retroviral integration occurs, because a retrovirus cannot actually target sites. It is just where they happen to integrate. I’d prefer the term “integration site”, but “target site” is entrenched in the literature now. TARGET_SITE_DNA is the host DNA before an integration. TARGET_SITE_DUP indicates a duplicate of the target site DNA which is always created upon integration.
Here are the crucial items to consider.
The origin of LTRs
The design* of LTRs.
The uniqueness of LTR “design”.
How DNA gets removed to create solos.
The fact that solos and doubles exist as alternative alleles.
The fact that there are solos that are not fixed.
*Dawkins coined the term “designoid” in his book, “Climbing Mount Improbable”, to indicate features that appear, superficially at least,to be designed. But I shall continue to use “design” in scare-quotes.
Item 1: The origin of LTRs
The only well-established biological source of paired LTR structures flanking an integrated sequence is retroviral or LTR-retroelement integration. Their LTRs provide transcription promoters without which the cell will not transcribe the full viral DNA back into RNA, perpetuating the viral replication cycle. As we shall see, solo LTRs derive from these integrations.
Item 2: LTR “design”
The “design” of LTRs. If we look closely at the LTRs in both the solo and the double cases, we find that the “design” of their structures is the same. In fully functional doubles, they meet the needs of retroviral replication. LTRs contain promoter and enhancement elements that recruit the host transcription machinery, allowing transcription of the proviral genome to begin at the correct transcription start site. Transcription is required upon each iteration of the retroviral replication cycle.
The overall structure of any LTR is U3 - R - U5 where
U3 contains promoter and enhancer elements,
R is a short sequence that is transcribable, and
U5 is a downstream regulatory sequence.
LTRs and their adjacent proviral regions retain replication-related motifs such as primer binding sites and polypurine tracts.
Primer binding sites (PBSs) matching host tRNAs
Required to start reverse transcription - a purely retroviral function.
Cellular DNA never needs to bind tRNA for replication.
There is no need for a host promoter to contain such a site.
Polypurine tracts (PPTs)
Primers for starting plus-strand DNA synthesis during reverse transcription.
Signals tightly coupled to the promoter.
The poly(A) tail produced is important for the nuclear export, translation and stability of mRNA.
LTR-associated sequences (such as PBS and PPT regions) originate from retroviral replication requirements and have no known role in ordinary cellular gene regulation. These molecular “tools” make sense in terms of a retroviral replication cycle.
For more details, see Wikipedia’s entries, Long terminal repeat and Endogenous retrovirus, the latter of which discusses solos.
The LTRs in solos and doubles are also bracketed by host DNA and target site duplication. This is a powerful indication that solo LTRs and the LTRs in doubles have the same source or cause.
So when a retrovirus integrates its genetic payload with the DNA of a host organism, two identical LTRs are created, bracketing it. This is bracketed in turn by a short sequence of host DNA and its duplicate. These identical ends are significant when one considers Item 4 below, the creation and formation of solos.
As a side effect, LTRs also promote the transcription of ‘native’ genetics as well as that of the enclosed viral genetics. This is often used to argue that this is the reason for all LTR “designs”, but it is more parsimoniously explained as happenstance. LTRs in doubles and singles promote native genetics in exactly the same way as they promote the enclosed viral genetics in a double.
Double LTRs are created upon reverse transcription. Normal cellular processes do not create regulatory sequences at both ends of an inserted DNA segment. No known cellular mechanism produces a structure consisting of a solitary LTR flanked by target site duplications identical to those created during retroviral integration.
This shows that the statement “solo LTRs do not include any viral genetic material” is misleading, because the LTR sequence itself is derived from retroviral DNA.
Item 3: The uniqueness of LTR “design”
The structure of doubles is unique. No other promoters or enhancers have the same structure, duplicating symmetrically around coding regions, except for solos, which also have a target site and its duplicate, exactly as they exist, framing a double. This makes no sense except in the light of Item 4.
Item 4. How DNA gets removed, creating solos
The two LTRs in doubles are identical upon the integration of a provirus.
When two nearly identical DNA sequences occur in the same orientation, the cell’s DNA repair machinery may align them and recombine them. In the case of a provirus, the two LTRs are initially identical. Recombining these LTRs and deleting the intervening viral genes leaves behind a single LTR at the original integration site, typically preserving the flanking host DNA and target site duplications. “These two bits look the same, so we’ll cut one of them out, and everything in between, and join up what is left.”
This goes by the fancy name of homologous (same) recombination (re-joining), a type of genetic recombination in which genetic formation is exchanged between two similar or identical (homologous) sequences and is a normal part of the cell’s DNA repair activity. It is a predicted outcome of having homologous structures in the DNA. It happens in various contexts, including DNA break repairs. It can recognise that the LTR “brackets” in a double are identical or nearly so, and can perform a recombination in which the ERV’s viral “guts” gets snipped out, leaving just one LTR, a solo.
Importantly, this process deletes the internal viral genes but usually preserves the surrounding host DNA and the original target site duplications, leaving a characteristic genomic “scar” of retroviral integration
Item 5: Alternative alleles. Unfixed Solo LTRs
In some DNA loci of a species’ genome, we find a solo in some individuals and a double in other individuals. See Item 6. This is a very strong indication that recombination is occurring with the doubles. It is very hard to imagine any other processes that would place a double at a host DNA locus in one individual and a solo at the same DNA locus in another individual of the same species.
Item 6: Unfixed Solo LTRs and Proof of Recombination
In combination with Item 5, it has been found that there are polymorphisms where the alleles may be
what are called “pre-integration alleles” (no double or solo),
or doubles,
or singles.
Hughes JF, Coffin JM. Human endogenous retrovirus K solo-LTR formation and insertional polymorphisms: implications for human and viral evolution. Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1668-72. doi: 10.1073/pnas.0307885100. Epub 2004 Feb 2. PMID: 14757818; PMCID: PMC341815.
Abstract
Human endogenous retroviruses (HERVs) are a potential source of genetic diversity in the human genome. Although many of these elements have been inactivated over time by the accumulation of deleterious mutations or internal recombination leading to solo-LTR formation, several members of the HERV-K family have been identified that remain nearly intact and probably represent recent integration events. To determine whether HERV-K elements have caused recent changes in the human genome, we have undertaken a study of the level of HERV-K polymorphism that exists in the human population. By using a high-resolution unblotting technique, we analyzed 13 human-specific HERV-K elements in 18 individuals. We found that solo LTRs have formed at five of these loci. These results enable the estimation of HERV solo-LTR formation in the human genome and indicate that these events occur much more frequently than described in inbred mice. Detailed sequence analysis of one provirus shows that solo-LTR formation occurred at least three separate times in recent history. An unoccupied preintegration site also was present at this locus in two individuals, indicating that although the age of this provirus is estimated to be approximately 1.2 million years, it has not yet become fixed in the human population.
Remarks
Budinsky’s article claims that ERVs that are fixed in the population, which includes all solos, are parts of a supposed original genome, whereas unfixed ones are the result of endogenization by endogenous retoviruses.
There are a number of problems with this claim.
1. Basic parsimony. We know that exogenous retroviruses are a source of ERVs because we see endogenization happening right now. To propose that fixed ERVs are there as the result of a different, unevidenced cause is, in the words of Sir Isaac Newton, “multiplying entities beyond necessity”. Why complicate things when there is no good reason to?
2. Given two sequences, one for a fixed ERV and one for an unfixed one, there is nothing whatsoever within the sequences to distinguish them.
3. Even if it was conceded that fixed ERVs are original to the genome (it isn’t, but even if it was), the unfixed ones still require explanation.
4. Solo LTRs account for some 90% of ERVs in common loci in Homo and Pan. The remaining 10% (some 20,000) also require explanation.
5. The idea that all solo LTRs are fixed is incorrect.
6. The idea that solo LTRs do not contain retroviral material is also incorrect.
7. Homologous recombination perfectly accounts for the formation of solos as remnants of doubles.
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