On May 2, Casey Luskin had an online debate with Professor Daniel Stern Cardinale, an evolutionary biologist at Rutgers University. Dr. Stern Cardinale is also a YouTuber going by the name “Dr. Dan.” The question up for discussion was whether the preponderance of our genome is non-functional “junk” — evolutionary debris accumulated over the eons of life’s history. 

During the debate, a key aspect of Dr. Dan’s argument focused on a DNA element called LINE-1 elements, a type of transposable element (TE) which compose about 17 percent of the human genome.  Dr. Dan argued that although some LINE-1 elements have been found to be functional, many of these genetic elements are mutationally “degraded.” He uses that term because under his view, one part of some LINE elements, the ORF2 gene, which codes for the reverse transcriptase and endonuclease, is mutated such that it no longer works. Without those crucial enzymes, Dr. Dan thinks, they are so “degraded” that they can no longer fulfil their normal job — being transcribed into RNA and then reverse transcribing themselves back into DNA, inserting themselves into another part of the genome. In short, LINEs that cannot retrotranspose are what Dr. Dan calls “degraded.” In some cases this could be what happened, but an alternative perspective is that many of these LINEs really are part of the design of our genome and didn’t originate through “degradation.” Thus, we will put his term in quote marks throughout.

The big question, therefore, is whether Dr. Dan is correct to assume that these “degraded” LINE elements must be functionless junk. He forcefully maintained during the debate that they cannot have any function if they are “degraded” — but we’ve seen time and time again that what was once considered “junk” turns out to have the potential to encode many important functions. 

So, let’s investigate the heart of Dr. Dan’s argument: If large percentages of our LINE elements are “degraded,” does this mean they must be functionless “junk”? The short answer is “No” and the long answer is “HECK NO! — And we’ve got numerous citations from the peer-reviewed literature to show this is the case.”

Who Is Right? 

We must first note that it’s well accepted that TEs such as LINEs can have many vital functions, often related to regulating gene expression. A review by Lawson et al. 2023 says: “TE-derived sequences can function as cis-regulatory elements such as enhancers, promoters and silencers.” Similarly, another review by Ali et al. 2021 explains:

TEs encode for regulatory RNAs with their sequences showed to be present in a substantial fraction of miRNAs and long non-coding RNAs (lncRNAs), indicating the TE origin of these RNAs. Furthermore, TEs sequences were found to be critical for regulatory functions of these RNAs, including binding to the target mRNA. TEs thus provide crucial regulatory roles by being part of cis-regulatory and regulatory RNA sequences. 

Lawson HA, Liang Y, Wang T. Transposable elements in mammalian chromatin organization. Nat Rev Genet.2023 Oct;24(10):712-723

Dr. Dan’s argument essentially comes down to assuming that if a LINE element is “degraded” then it cannot have function — but this assumption is refuted by a large body of scientific literature showing that what he calls “degraded” LINE elements can indeed have function. In the end, Dr. Dan’s argument is revealed as a classic example of evolutionist reasoning that if we don’t know what something does, then it must not do anything. It’s this sort of science-stopping reasoning that created the now-defunct “junk DNA” paradigm in the first place. 

Enter the Functional World of LINEs

LINE elements possess open reading frames: ORF1 and ORF2. ORF2, in particular, is critical for successful retrotransposition, since it encodes a protein possessing reverse transcriptase and endonuclease activity. Sometimes, these open reading frames have accumulated mutations such that the LINE element is no longer able to retrotranspose. Does this preclude them from having functions that do not depend upon retrotransposition? Not at all. For example, Rangwala et al., in a 2009 paper published in Genome Biology, observed that,

Elements that have lost function for both ORF1 and ORF2 may still contribute promoter and polyadenylation sites that can interfere with the transcriptional regulation of a genomic region. For instance, transcription through an older element on human chromosome 10 appears to be involved in the formation of a neocentromere. L1s also might be important in recruiting DNA methylation and heterochromatin formation on the inactive X chromosome. In plants, the presence of transcription through a retrotransposon results in altered regulation of neighboring genes. [Internal citations omitted.]

Rangwala SH, Zhang L, Kazazian HH Jr. Many LINE1 elements contribute to the transcriptome of human somatic cells. Genome Biol. 2009;10(9):R100

They further note that,

L1s in somatic tissues have been thought to be mainly quiescent: neither transcribed nor retrotransposing, rendered silent by cytosine methylation and histone modification. Those L1s that are expressed are often prematurely aborted through internal splicing or polyadenylation. Yet, growing evidence questions the assumption that all L1s are suppressed: L1s may in fact be both transcribed and mobile, not just in the germline, but also in the early embryo, and in certain other tissues. It is unclear how many of the thousands of L1 promoters in the genome are active, as sequences derived from repetitive DNA are typically excluded from most genome-wide transcriptome analyses. [Internal citations omitted.] 

Rangwala SH, Zhang L, Kazazian HH Jr. Many LINE1 elements contribute to the transcriptome of human somatic cells. Genome Biol. 2009;10(9):R100

But we’re just getting started.

More Function: Lining Up LINES

There exists a wealth of literature that demonstrates en masse functions of LINE-1 elements — functions that include many LINE elements together and that clearly are independent of the ability of these elements to retrotranspose. Furthermore, the vast majority of the en masse fragments are “degraded,” and so lack the ability to retrotranspose. We are including a list below offering a sample of these papers. Those that are related to young or hominid-specific elements are identified as such — although a minority, these are still quite numerous. Others pertain to all age classes of the repeat unless otherwise stated.

1) L1s and DNA methylation:

• Young, full-length elements are differentially methylated in the earliest stages of embryogenesis:

Min B, Park JS, Jeong YS, Jeon K, Kang YK. 2020. Dnmt1 binds and represses genomic retroelements via DNA methylation in mouse early embryos. Nucleic Acids Research 48: 8431-8444.

• Different age/length classes of L1s have cell-/family-/locus-specific methylation patterns that spread in cis, and in association with specific transcription factors: 

Lanciano S, Philippe C, Sarkar A, Pratella D, Domrane C, Doucet AJ, van Essen D, Saccani S, Ferry L, Defossez PA, Cristofari G. 2024. Locus-level L1 DNA methylation profiling reveals the epigenetic and transcriptional interplay between L1s and their integration sites. Cell Genomics 4: 100498. 

• Young, full-length elements are demethylated in neural cell lineages, enabling them to act as alternative promoters for a range of protein-coding loci:

Jönsson ME, Ludvik Brattås P, Gustafsson C, Petri R, Yudovich D, Pircs K, Verschuere S, Madsen S, Hansson J, Larsson J, Månsson R, Meissner A, Jakobsson J. 2019. Activation of neuronal genes via LINE-1 elements upon global DNA demethylation in human neural progenitors. Nature Communications 10: 3182.

2) Intronic L1s and locus expression — transcriptional interference and “molecular rheostats”:

• There are roughly 650,000 human L1 sequences located in introns:

Smit AF. 1999. Interspersed repeats and other mementos of transposable elements in mammalian genomes. Current Opinion in Genetics & Development 9: 657-663; see also Attig et al., 2018 below. 

• L1s as “fine-tuners” of human RNA production:

Han JS, Szak ST, Boeke JD. 2004. Transcriptional disruption by the L1 retrotransposon and implications for mammalian transcriptomes. Nature 429: 268-274.

Kaer K, Branovets J, Hallikma A, Nigumann P, Speek M. 2011. Intronic L1 retrotransposons and nested genes cause transcriptional interference by inducing intron retention, exonization and cryptic polyadenylation. PLoS One6: e26099.

3) Young L1s as intronic cis-regulatory elements by way of H3K9me3 chromatin mark:

Pelinski Y, Hidaoui D, Stolz A, Hermetet F, Chelbi R, Diop MK, Chioukh AM, Porteu F, Elvira-Matelot E. 2022. NF-κB signaling controls H3K9me3 levels at intronic LINE-1 and hematopoietic stem cell genes in cis. Journal of Experimental Medicine 219: e20211356.

4) L1s (in general) as heterochromatin inducers:

Vogel MJ, Guelen L, de Wit E, Peric-Hupkes D, Lodén M, Talhout W, Feenstra M, Abbas B, Classen AK, van Steensel B. 2006. Human heterochromatin proteins form large domains containing KRAB-ZNF genes. Genome Research 16: 1493-1504.

Ye Y, Zhang S, Gao L, Zhu Y, Zhang J. 2023. Deciphering hierarchical chromatin domains and preference of genomic position forming boundaries in single mouse embryonic stem cells. Advanced Science 10: e2205162.

5) L1s (in general) carry antisense promoters:

• With respect to comparatively old primate L1s:

Macia A, Munoz-Lopez M, Cortes JL, Hastings RK, Morell S, Lucena-Aguilar G, Marchal JA, Badge RM, Garcia-Perez JL. 2011. Epigenetic control of retrotransposon expression in human embryonic stem cells. Molecular and Cellular Biology 31: 300-316.

• Indeed, the 3′ region of variably truncated (“degraded”) L1s allows for antisense transcription; in the study below it was found that of L1-associated antisense RNAs 2.6 percent are derived from the human-specific subfamily, 31.1 percent are derived from older primate-specific subfamilies, and 66.3 percent are derived from mammalian subfamilies:

Faulkner GJ, Kimura Y, Daub CO, Wani S, Plessy C, Irvine KM, Schroder K, Cloonan N, Steptoe AL, Lassmann T, et al. 2009. The regulated retrotransposon transcriptome of mammalian cells. Nature Genetics 41: 563-571.

• That older L1s give rise to antisense RNAs is confirmed here:

Criscione SW, Theodosakis N, Micevic G, Cornish TC, Burns KH, Neretti N, Rodić N. 2016. Genome-wide characterization of human L1 antisense promoter-driven transcripts. BMC Genomics 17: 463.

6) (Young) L1s as enhancers in embryonic stem cells:

Meng S, Liu X, Zhu S, Xie P, Fang H, Pan Q, Fang K, Li F, Zhang J, Che Z, Zhang Q, Mao G, Wang Y, Hu P, Chen K, Sun F, Xie W, Luo Z, Lin C. 2023. Young LINE-1 transposon 5′ UTRs marked by elongation factor ELL3 function as enhancers to regulate naïve pluripotency in embryonic stem cells. Nature Cell Biology 25: 1319-1331.

Sakamoto M, Ishiuchi T. 2024. YY1-dependent transcriptional regulation manifests at the morula stage. microPublication Biology 2024:10.17912/micropub.biology.001108.

7) (Young) L1 RNAs as cis-regulatory determinants in embryogenesis and later:

Harris CR, Dewan A, Zupnick A, Normart R, Gabriel A, Prives C, Levine AJ, Hoh J. 2009. p53 responsive elements in human retrotransposons. Oncogene 28: 3857-3865.

Fadloun A, Le Gras S, Jost B, Ziegler-Birling C, Takahashi H, Gorab E, Carninci P, Torres-Padilla ME. 2013. Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA. Nature Structural & Molecular Biology 20: 332-338.

Jachowicz JW, Bing X, Pontabry J, Boskovic A, Rando OJ, Torres‐Padilla ME. 2017. LINE‐1 activation after fertilization regulates global chromatin accessibility in the early mouse embryo. Nature Genetics 49: 1502-1510.

Wang XF, Xie SM, Guo SM, Su P, Zhou LQ. 2020. Dynamic pattern of histone H3 core acetylation in human early embryos. Cell Cycle 19: 2226-2234.

Ansaloni F, Gustincich S, Sanges R. 2023. In silico characterisation of minor wave genes and LINE-1s transcriptional dynamics at murine zygotic genome activation. Frontiers in Cell and Developmental Biology 11: 1124266.

8) Primate-specific L1s and heterochromatin regions:

Tunbak H, Enriquez-Gasca R, Tie CHC, Gould PA, Mlcochova P, Gupta RK, Fernandes L, Holt J, van der Veen AG, Giampazolias E, Burns KH, Maillard PV, Rowe HM. 2020. The HUSH complex is a gatekeeper of type I interferon through epigenetic regulation of LINE-1s. Nature Communications 11: 5387.

Stamidis N, Żylicz JJ. 2023. RNA-mediated heterochromatin formation at repetitive elements in mammals. The EMBO Journal 42: e111717.

9) L1s (in general) as tissue-specific cis-regulatory sequences: 

Roller M, Stamper E, Villar D, Izuogu O, Martin F, Redmond AM, Ramachanderan R, Harewood L, Odom DT, Flicek P. 2021. LINE retrotransposons characterize mammalian tissue-specific and evolutionarily dynamic regulatory regions. Genome Biology 22: 62.

10) L1 subfamilies and RNA processing:

Onoguchi M, Zeng C, Matsumaru A, Hamada M. 2021. Binding patterns of RNA-binding proteins to repeat-derived RNA sequences reveal putative functional RNA elements. NAR Genomics & Bioinformatics 3: lqab055.

• Young L1-derived sequences tend to be located far from exons and are bound by dozens of RNA-binding proteins (RBPs), which inhibit splicing and 3′ end processing within and around those elements. In contrast, older L1-derived sequences allow the binding of splice-promoting RBPs and their tissue-specific incorporation into exons and other segments of transcripts:

Attig J, Agostini F, Gooding C, Chakrabarti AM, Singh A, Haberman N, Zagalak JA, Emmett W, Smith CWJ, Luscombe NM, Ule J. 2018. Heteromeric RNP assembly at LINEs controls lineage-specific RNA processing. Cell174: 1067-1081.

11) L1 transcripts and m⁶A demethylation:

• The protein FTO is involved in the de-editing of L1 transcripts, which regulates both the local chromatin state and levels of L1 RNA in early embryogenesis (and oogenesis):

Wei J, Yu X, Yang L, Liu X, Gao B, Huang B, Dou X, Liu J, Zou Z, Cui XL, Zhang LS, Zhao X, Liu Q, He PC, Sepich-Poore C, Zhong N, Liu W, Li Y, Kou X, Zhao Y, Wu Y, Cheng X, Chen C, An Y, Dong X, Wang H, Shu Q, Hao Z, Duan T, He YY, Li X, Gao S, Gao Y, He C. 2022. FTO mediates LINE1 m⁶A demethylation and chromatin regulation in mESCs and mouse development. Science 376: 968-973.

12) L1 RNA abundance and T-cell quiescence:

• Marasca F, Sinha S, Vadalà R, Polimeni B, Ranzani V, Paraboschi EM, Burattin FV, Ghilotti M, Crosti M, Negri ML, Campagnoli S, Notarbartolo S, Sartore-Bianchi A, Siena S, Prati D, Montini G, Viale G, Torre O, Harari S, Grifantini R, Soldà G, Biffo S, Abrignani S, Bodega B. 2022. LINE1 are spliced in non-canonical transcript variants to regulate T cell quiescence and exhaustion. Nature Genetics 54: 180-193.

13) Antisense L1 RNAs and the nuclear matrix/scaffold:

• Of 17,190 repetitive elements that were found to be associated with the MATR3 protein, 40.99 percent or approximately 7,046 were bound to L1 RNA sites — the majority were in antisense transcripts:  

Zhang Y, Cao X, Gao Z, Ma X, Wang Q, Xu X, Cai X, Zhang Y, Zhang Z, Wei G, Wen B. 2023. MATR3-antisense LINE1 RNA meshwork scaffolds higher-order chromatin organization. EMBO Reports 24: e57550.

(It should be noted that interactions between nuclear matrices/scaffolds and L1s (of which an internal portion used to be called the KpnI element) were detected back in the mid 1980s: Chimera JA, Musich PR. 1985. The association of the interspersed repetitive KpnI sequences with the nuclear matrix. Journal of Biological Chemistry260: 9373-9379.)

14) Sense L1 RNAs and the nuclear matrix/scaffold:

• L1 transcripts are bound by Kap1/Trim28 and Nucleolin to silence Dux, which is the key regulator of 2-cell embryonic transcription, as well as up-regulating rRNA synthesis and embryonic stem cell self-renewal: 

Percharde M, Lin CJ, Yin Y, Guan J, Peixoto GA, Bulut‐Karslioglu A, Biechele S, Huang B, Shen X, Ramalho‐Santos M. 2018. A LINE1‐nucleolin partnership regulates early development and ESC identity. Cell 174: 391-405.

15) L1 transcripts (in general) form a coat around euchromatin regions: 

• Hall LL, Carone DM, Gomez AV, Kolpa HJ, Byron M, Mehta N, Fackelmayer FO, Lawrence JB. 2014. Stable C0T‐1 repeat RNA is abundant and is associated with euchromatic interphase chromosomes. Cell 156: 907-919.

Creamer KM, Kolpa HJ, Lawrence JB. 2021. Nascent RNA scaffolds contribute to chromosome territory architecture and counter chromatin compaction. Molecular Cell 81: 3509-3525.

16) L1 RNAs and (neuronal progenitor) cell differentiation:

Mangoni D, Simi A, Lau P, Armaos A, Ansaloni F, Codino A, Damiani D, Floreani L, Di Carlo V, Vozzi D, Persichetti F, Santoro C, Pandolfini L, Tartaglia GG, Sanges R, Gustincich S. 2023. LINE-1 regulates cortical development by acting as long non-coding RNAs. Nature Communications 14: 4974.

Toda T, Bedrosian TA, Schafer ST, Cuoco MS, Linker SB, Ghassemzadeh S, Mitchell L, Whiteley JT, Novaresi N, McDonald AH, Gallina IS, Yoon H, Hester ME, Pena M, Lim C, Suljic E, AlFatah Mansour A, Boulard M, Parylak SL, Gage FH. 2024. Long interspersed nuclear elements safeguard neural progenitors from precocious differentiation. Cell Reports 43: 113774. 

Garza R, Atacho DAM, Adami A, Gerdes P, Vinod M, Hsieh P, Karlsson O, Horvath V, Johansson PA, Pandiloski N, Matas-Fuentes J, Quaegebeur A, Kouli A, Sharma Y, Jönsson ME, Monni E, Englund E, Eichler EE, Gale Hammell M, Barker RA, Kokaia Z, Douse CH, Jakobsson J. 2023. LINE-1 retrotransposons drive human neuronal transcriptome complexity and functional diversification. Science Advances 9: eadh9543.

17) L1s and X-chromosome inactivation:

• There is a twofold enrichment of L1s on the X chromosome with approximately 35 percent of its DNA in mouse and human being derived from this sequence, mainly those that transposed less than 100 million years ago, and this distribution of full-length and incomplete (“degraded”) elements corresponds to foci that enable/initiate its inactivation in embryogenesis:

Fujita PA, Rhead B, Zweig AS, Hinrichs AS, Karolchik D, Cline MS, Goldman M, Barber GP, Clawson H, Coelho A, Diekhans M, Dreszer TR, Giardine BM, Harte RA, Hillman-Jackson J, Hsu F, Kirkup V, Kuhn RM, Learned K, Li CH, Meyer LR, Pohl A, Raney BJ, Rosenbloom KR, Smith KE, Haussler D, Kent WJ. 2011. The UCSC Genome Browser database: update 2011. Nucleic Acids Research 39 (Database issue): D876-882.

Bailey JA, Carrel L, Chakravarti A, Eichler EE. 2000. Molecular evidence for a relationship between LINE-1 elements and X chromosome inactivation: the Lyon repeat hypothesis. Proceedings of National Academy of Science, U.S.A. 97: 6634-6639.

Chow JC, Ciaudo C, Fazzari MJ, Mise N, Servant N, Glass JL, Attreed M, Avner P, Wutz A, Barillot E et al.2010. LINE‐1 activity in facultative heterochromatin formation during X chromosome inactivation. Cell 141: 956-969.

Namekawa SH, Payer B, Huynh KD, Jaenisch R, Lee JT. 2010. Two-step imprinted X inactivation: repeat versus genic silencing in the mouse. Molecular and Cellular Biology 30: 3187-3205.

Calabrese JM, Sun W, Song L, Mugford JW, Williams L, Yee D, Starmer J, Mieczkowski P, Crawford GE, Magnuson T. 2012. Site-specific silencing of regulatory elements as a mechanism of X inactivation. Cell 151: 951-963.

Hall LL, Creamer KM, Byron M, Lawrence JB. 2024. Differences in Alu vs L1-rich chromosome bands underpin architectural reorganization of the inactive-X chromosome and SAHFs. bioRxiv [Preprint]. 2024 Jan 9:2024.01.09.574742.

• A similar regulatory effect can be detected in autosomal regions:

Loda A, Brandsma JH, Vassilev I, Servant N, Loos F, Amirnasr A, Splinter E, Barillot E, Poot RA, Heard E, Gribnau J. 2017. Genetic and epigenetic features direct differential efficiency of Xist-mediated silencing at X-chromosomal and autosomal locations. Nature Communications 8: 690.

18) L1s and chromosome organization in 3D/4D:

• Locally the L1 transcripts remain close to the regions from which they are transcribed:

Lu JY, Shao W, Chang L, Yin Y, Li T, Zhang H, Hong Y, Percharde M, Guo L, Wu Z et al. 2020. Genomic repeats categorize genes with distinct functions for orchestrated regulation. Cell Reports 30: 3296-3311.

Lu JY, Chang L, Li T, Wang T, Yin Y, Zhan G, Han X, Zhang K, Tao Y, Percharde M et al. 2021. Homotypic clustering of L1 and B1/Alu repeats compartmentalizes the 3D genome. Cell Research 31: 613-630.

Liang Z, Fu XD. 3D genome encoded by LINE and SINE repeats. 2012. Cell Research 31: 603-604.

• Across four species (dog, mouse, macaque, and human) L1s contribute from 3.9 percent to 25.4 percent of chromatin-loop anchor sites:

Choudhary MNK, Quaid K, Xing X, Schmidt H, Wang T. 2023. Widespread contribution of transposable elements to the rewiring of mammalian 3D genomes. Nature Communications 14: 634.

• L1s also form TAD boundaries by enrichment in RNA polymerase II, the generation of L1 chimeric RNAs, and this role is differentially counteracted by the SAFB nuclear-matrix protein:

Hong Y, Bie L, Zhang T, Yan X, Jin G, Chen Z, Wang Y, Li X, Pei G, Zhang Y, Hong Y, Gong L, Li P, Xie W, Zhu Y, Shen X, Liu N. 2024. SAFB restricts contact domain boundaries associated with L1 chimeric transcription. Molecular Cell 84: 1637-1650.

19) L1s and the nuclear lamina:

• Interactions between chromatin/DNA and the nuclear lamina take place by way of 1,100 to 1,400 Lamina Associated Domains (LADs), which are interspersed across all chromosomes and that have a median length of around 500,000 basepairs. L1s are distributed throughout these segments:   

Zullo JM, Demarco IA, Piqué-Regi R, Gaffney DJ, Epstein CB, Spooner CJ, Luperchio TR, Bernstein BE, Pritchard JK, Reddy KL, Singh H. 2012. DNA sequence-dependent compartmentalization and silencing of chromatin at the nuclear lamina. Cell 149: 1474-1487.

Meuleman W, Peric-Hupkes D, Kind J, Beaudry JB, Pagie L, Kellis M, Reinders M, Wessels L, van Steensel B. 2013. Constitutive nuclear lamina-genome interactions are highly conserved and associated with A/T-rich sequence. Genome Research 23: 270-280.

Kind J, Pagie L, de Vries SS, Nahidiazar L, Dey SS, Bienko M, Zhan Y, Lajoie B, de Graaf CA, Amendola M, Fudenberg G, Imakaev M, Mirny LA, Jalink K, Dekker J, van Oudenaarden A, van Steensel B. 2015. Genome-wide maps of nuclear lamina interactions in single human cells. Cell 163: 134-147.

• The study below found that the SIRT7 nuclear-lamina factor binds to 72,622 dispersed loci, of which 80 percent occur at L1 elements. This is a contribution of the latter to around 58,098 sites:

Vazquez BN, Thackray JK, Simonet NG, Chahar S, Kane-Goldsmith N, Newkirk SJ, Lee S, Xing J, Verzi MP, An W, Vaquero A, Tischfield JA, Serrano L. 2019. SIRT7 mediates L1 elements transcriptional repression and their association with the nuclear lamina. Nucleic Acids Research 47: 7870-7885.

20) L1s (en masse) and cell type-specific nuclear organizations:

Solovei I, Kreysing M, Lanctôt C, Kösem S, Peichl L, Cremer T, Guck J, Joffe B. 2009. Nuclear architecture of rod photoreceptor cells adapts to vision in mammalian evolution. Cell 137: 356-368.

Ostromyshenskii DI, Chernyaeva EN, Kuznetsova IS, Podgornaya OI. 2018. Mouse chromocenters DNA content: sequencing and in silico analysis. BMC Genomics 19: 151.

Ormundo LF, Machado CF, Sakamoto ED, Simões V, Armelin-Correa L. 2020. LINE-1 specific nuclear organization in mice olfactory sensory neurons. Molecular and Cellular Neuroscience 105: 103494.

Sorry for the Literature Dump

We realize the citations above amount to another literature dump, but we wanted the reader to get a little taste of the depth of evidence for function of LINE elements — even when they are in what Dr. Dan called a “degraded” state. 

During the debate, Dr. Dan argued that if a genetic element appears mutationally degraded then we ought to assume it has no function. Dr. Dan’s reasoning is not at all uncommon — as Casey Luskin documented here, many evolutionary scientists have presumed that junk DNA would not have function and therefore, as an article in Nature said, “it would be folly” to spend much time seeking function. Even the journal Science admitted that such reasoning has “repelled mainstream researchers from studying noncoding genetic material.” In other words, the evolutionary view of junk DNA, held by Dr. Dan and others, is stopping science and holding scientists back from discovering functions for “degraded” LINE elements. 

The evidence we’ve provided here demonstrates that even so-called “degraded” LINE elements can have function. This is well documented in the literature. It shows that Dr. Dan’s assumption of non-functionality for “degraded” LINES should be overturned. Given that we know of so many cases where “degraded” LINEs have function, the last thing we should be doing is assuming they are “junk.” 

But we’re ID theorists who take the idea of function for junk DNA very seriously. We propose that a better assumption would be, “If it is transcribed, then that is prima facie evidence of function.” And the continually growing evidence of specific functions for “junk DNA” — including “degraded” LINES that we’ve documented here — increasingly confirms that this is the best way of approaching the genome.