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Waste Not: Research Finds that “Far from Junk DNA,” ERVs Perform “Critical Cellular Functions”

Evolution News

junk DNA

In the past, reporting by Evolution News has documented a variety of important functions for endogenous retroviruses (ERVs) and other transposable elements and retrotransposons. These, of course, have frequently been called “junk DNA,” mere evolutionary waste or flotsam, by critics of intelligent design. Evidence of this widespread function is nothing new. As a 2017 paper in Nature Reviews Genetics noted, “Transposable elements (TEs) are a prolific source of tightly regulated, biochemically active non-coding elements, such as transcription factor-binding sites and non-coding RNAs.” 

Now a pair of new articles in Nature Genetics acknowledge just how widespread ERV and retrotransposon functionality is. One is a research paper and the other is a summary article. The summary article opens by explicitly denying that retrotransposons are junk DNA:

Far from being junk DNA, the pervasive retrotransposons that populate the genome have a powerful capacity to influence genes and chromatin. A new study demonstrates how the transcription of one such element, HERV-H, can modify the higher-order 3D structure of chromatin during early primate development.

The summary further notes that “many ERVs have been co-opted for critical cellular functions.” It reviews some of these functions:

For example, ERVs frequently act to distribute regulatory information and thus confer genes with new patterns of expression and function. Similarly, multiple ERVs have been re-purposed as novel genes themselves, including the ERV envelope-derived syntactins that drive trophoblast fusion and establish the placental fetal–maternal interface. Now, Zhang et al. have identified an additional activity of co-opted ERVs — the alteration of the genome’s 3D structure itself — that may have the capacity to substantially affect gene regulation.

Research and Rhetoric

Looked at from a rhetorical perspective, Nature Genetics is clearly very sensitive about the implications of the study. After all, it shows that ERVs have extremely important functions, which is a bitter pill for many ID opponents. Nearly every time the summary describes an ERV as “functional” the word “co-opted” is placed nearby just to remind you that the ERVs really started off as something like junk and were “co-opted” by evolution to have a function. Words like “co-opted” are what the late National Academy of Sciences member Philip Skell called called in The Scientist “narrative gloss” — words that have no explanatory value but are brought in after the fact to make a connection to evolution. As Skell wrote:

I found that Darwin’s theory had provided no discernible guidance, but was brought in, after the breakthroughs, as an interesting narrative gloss.

Indeed. The evidence shows these ERVs are functional, but not only that. ERVs have crucial functions that help regulate genes and even determine cell types. Claiming they were “co-opted” is mere uninformative gloss. To understand the nature of their function, one must turn to the research itself.

The research paper here, “Transcriptionally active HERV-H retrotransposons demarcate topologically associating domains in human pluripotent stem cells,” starts by noting that the three-dimensional structure of chromosomes is crucial for building gene regulatory networks in animals:

The three-dimensional organization of chromosomes enables long-range interactions between enhancers and promoters that are critical for building complex gene regulatory networks in multicellular species.

That opening comment by itself refutes claims from some evolutionists that the shared three-dimensional structure of chromosomes across different species — often called synteny — is meaningless and reflects only their common ancestry, rather than important functional requirements. But as the paper explains, the three-dimensional organization of chromosome is “critical” for building gene regulatory networks (GRNs) that govern the development and growth of an organism.  

Moving Right Along

The paper explains that chromosomes have “a dynamic but non-random hierarchical structure” where they are organized into transcriptionally active, and transcriptionally silent regions. These regions are further broken down into “topologically associating domains (TADs),” which are basically chromosome regions that have important “intradomain interactions.” TAD domains are cell-type specific and species specific — in other words specifying domains of chromosome activity helps determine what kind of proteins will be produced, which helps determine what kind of cell a cell will become. Specified cell types ultimately produce tissues, which produce organs, which produce physiological systems, which produce an organism, which define a species. It’s all hierarchically regulated and it starts at the level of chromosomes with TAD domains. 

Sound Designed to You?

TAD boundaries on chromosomes are marked by bundles of proteins, some of which are called CCCTC-binding factors (CTCFs). And it turns out that CTCF binding locations on chromosomes are often controlled by so-called “transposable elements” — those supposed junk DNA elements that make up some 50 percent of the genome. But how important are transposable elements for this role? The paper notes that “how much transposable elements play a role in shaping the genome architecture during evolution has yet to be directly tested, particularly in primates.” Again, the words “during evolution” are more gloss that really just means “important for function.”  

The Paper’s Central Finding

And now we come to the central finding of the paper — that a type of endogenous retrovirus (ERV) is critical for defining TAD boundaries:

By interrogating the dynamic remodeling of chromatin architecture during human cardiomyocyte differentiation, we discovered a class of primate-specific endogenous retrotransposons — human endogenous retrovirus subfamily H (HERV-H) — that is involved in establishing TAD boundaries in human pluripotent stem cells (hPSCs). … [C]omparative analysis of the chromatin architecture in primate and non-primate species supports a role for actively transcribed HERV-H elements in demarcating primarily hominid pluripotent stem cell (PSC)-specific TADs. Overall, our results provide direct evidence for retrotransposon elements in actively shaping the chromatin architecture in specific cell types during evolution.

“During evolution”? Right, that’s more gloss, adding nothing to the empirical findings of this study. Again, these ERVs are crucial for defining TAD domain boundaries, which helps shape chromosome architecture, which helps determine cell types, which, as we saw, form the crucial foundation for a hierarchically controlled network that ultimately builds an organism. Here’s the research paper’s conclusion:

Here, we provide multiple lines of evidence showing that the primate-specific HERV-H retroviral elements can delineate TAD boundaries in hPSCs. Previous studies suggested that HERV-H elements integrated into the human genome during primate evolution to regulate human-specific pluripotency by creating novel chimeric transcripts (ESRG, linc-ROR and LINC00458) and providing potential binding sites to recruit pluripotency factors (NANOG, SOX2 and POU5F1). However, our findings indicate that HERV-H sequences may affect gene regulatory programs by also creating new hPSC-specific TAD boundaries that shape the chromatin architecture…. [O]ur findings suggest the intriguing possibility that other endogenous retrovirus families of repeats and/or other families of repetitive elements may have similar abilities to create TADs and insulation.

Evolutionary detritus is what neo-Darwinian theory would expect, but it’s not what we find. ERVs play extremely important functional roles in humans and many other animals. That’s not bad for something that great numbers of evolutionists have told us for decades is nothing more than junk DNA.

Photo credit: VanveenJF via Unsplash.