Conserved Non-Genic Sequences What'sNEW

There are about 60,000 CNGs in the human genome, about twice the number of coding genes — Mark Johnston and Gary D. Stormo (1)

They are under a stronger selective pressure than other functional genomic elements — Emmanouil T. Dermitzakis et al. (2)

The Study

A team of seven geneticists have found something amazing in the genomes of humans and at least twelve other mammals, "conserved non-genic sequences" (CNGs) of unknown function that are better conserved than genes, and twice as abundant.

It was already known that there are sequences outside of genes that are well-conserved between the human and mouse genomes. Untranslated regulatory sequences need to be conserved, for example. But regulatory sequences have more error tolerance than genes, not less. The faithfulness of conservation which this study observed in the CNGs is unprecedented. The most highly conserved ones have a nucleotide substitution rate, across the studied mammals, that is less than half that of protein-coding genes. In some examples, like the 100-nucleotide sequence shown below (2: Supplement), the match was almost too perfect, as if cross-contamination had occurred during PCR in the lab. But corroboration also comes from the dog genome that was sequenced elsewhere. "These findings imply that the CNGs are subject to a very strong and continual selective constraint, enabling them to remain largely unchanged for as long as 300 million years" (1).


Another surprise is the high number of the CNGs. Extrapolating from the human chromosome analyzed, the geneticists estimate that humans have over 65,000 of them, about twice the estimated number of human genes. Another multispecies comparison that employed different methods found a similar number.

The size of the CNGs is not readily apparent from the new article, but an earlier one by members of the same team (3) gives the actual sequences of all 2262 unknown blocks on human chromosome 21. Viewing them, we estimate those CNGs to have mean size of 100 to 150, and a maximum size of about 1,000 nucleotides.

Studies of more primitive species did not lead darwinists to anticipate this finding. "The CNGs in mammalian genomes are much more extensive and more highly conserved than anything seen in yeast, even though the evolutionary time separating [the studied] mammals... is longer (by a factor of at least 3) than that separating the different yeast species" (1).


For darwinism the CNGs are a conundrum — highly conserved sequences with no known function. Well, they must have a function, but what is it? And how could they have been gradually composed, and yet so tightly constrained?

In cosmic ancestry, new genetic programs must first be horizontally acquired and then installed. The operating software for a species capable of acquiring and installing new genetic programs would probably include a lot more than the transcribed genes. Some of this high-level software would probably need very precise encoding.

In cosmic ancestry, the CNGs themselves would have been horizontally acquired as well. The new data even seem to support that alternative according to criteria we stated in April 2002: "If a new genetic program arrives by the strong panspermia process, intervening species should possess either nearly identical versions of it... or nothing similar..." (4). These CNG's are even more nearly identical, among species from mice to humans, than we would have guessed.

What'sNEW since 2003

"Identification of constrained sequence elements across 239 primate genomes," by L.F.K. Kuderna, J.C. Ulirsch, S. Rashid et al., doi:10.1038/s41586-023-06798-8, Nature, 25 Jan 2024. These elements are predicted to regulate genes that are more intolerant to deleterious mutations in human populations and are significantly enriched for common genetic variants associated with variation in gene expression and complex human traits and diseases.
Perfect and imperfect views of ultraconserved sequence by Snetkova, V., Pennacchio, L.A., Visel, A. et al., doi:10.1038/s41576-021-00424-x, Nat Rev Genet, March 2022.
Across the human genome, there are nearly 500 'ultraconserved' elements: regions of at least 200 contiguous nucleotides that are perfectly conserved in both the mouse and rat genomes. Remarkably, the majority of these sequences are non-coding, and many can function as enhancers that activate tissue-specific gene expression during embryonic development. ...The intrigue around ultraconserved elements only grew with the observation that they are dispensable for viability.
On causal roles and selected effects: our genome is mostly junk by W. Ford Doolittle and Tyler D. P. Brunet, doi:10.1186/s12915-017-0460-9, BMC Biology, 05 Dec 2017.
Nuclear Long Noncoding RNAs: Key Regulators of Gene Expression, by Qinyu Sun et al., doi:10.1016/j.tig.2017.11.005, Trends in Genetics, online 17 Dec 2017.
The New RNA World: Growing Evidence for Long Noncoding RNA Functionality, by Allison Jandura and Henry M. Krause, doi:10.1016/j.tig.2017.08.002, Trends in Genetics, online 01 Sep 2017.
Poisons, antidotes, and selfish genes, by Nitin Phadnis, doi:10.1126/science.aan6119, Science, 09 Jun 2017. ...replicators that are specialists in ensuring their own transmission despite conferring no [immediate/apparent] benefit....
Mysterious unchanging DNA finds a purpose in life, by Elizabeth Pennisi, doi:10.1126/science.356.6341.892, Science, 02 Jun 2017.
Junk DNA: A Journey Through the Dark Matter of the Genome, by Nessa Carey, ISBN:9780231539418, Columbia University Press, Apr 2015.
What have we learned from doing all those genome sequences? by Michael Adams, doi:10.1186/1741-7007-11-109, BMC Biology, 31 Oct 2016. me one of the most startling results of the genomic revolution is what we don't know, rather than what we do. In general, for any genome that's sequenced, we only really know what about a third of the genes do.
James Shapiro, "Biological action in Read-Write genome evolution," at the Royal Society, London, 08 Nov 2016. ...Biological complexity scales with 'non-coding' DNA content rather than with protein-coding capacity in the genome.
Aoife McLysaght and Daniele Guerzoni, "New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation" [pdf], doi:10.1098/rstb.2014.0332, Philosophical Transactions B, 2015. ...It has now become clear that de novo origin of protein-coding genes from non-coding DNA is a consistent feature of eukaryotic genomes....
Critical roles of long noncoding RNAs in Drosophila spermatogenesis by Kejia Wen, Lijuan Yang, Tuanlin Xiong et al., doi:10.1101/gr.199547.115, p 1233-1244 v 26, Genome Res., Sep 2016.
21 Aug 2016: Can antagonistic evolution compose de novo genes?
'Junk DNA' tells mice—and snakes—how to grow a backbone by Diana Crow, Science, online 01 Aug 2016.
You are junk: Why it's not your genes that make you human by Colin Barras, New Scientist, 27 Jul 2016.
Genes in Hiding by Gertraud Burger, Sandrine Moreira and Matus Valach, doi:10.1016/j.tig.2016.06.005, Trends in Genetics, online 22 Jul 2016. While genomicists struggle with incognito genes, these genes are accurately decoded in the cell. ...Despite the heralded postgenomic era, genomics has yet to transit into adulthood.
CRISPR Screens to Discover Functional Noncoding Elements by Jason B. Wright and Neville E. Sanjana, doi:10.1016/j.tig.2016.06.004, Trends in Genetics, proof online 17 Jul 2016.
11 May 2016: Hidden exons in Chlamydomonas
Unlinking an lncRNA from Its Associated cis Element by Vikram R. Paralkar et al., doi:10.1016/j.molcel.2016.02.029, Molecular Cell, 07 Apr 2016; and commentary: ...How Fundamental DNA Sequences Govern Gene Activity, Perelman School of Medicine, University of Pennsylvania (+Newswise), 07 Apr 2016.
Analysis of 5' gene regions reveals extraordinary conservation of novel non-coding sequences in a wide range of animals, by Nathaniel J. Davies et al., doi:10.1186/s12862-015-0499-6, BMC Evolutionary Biology, 19 Oct 2015; and commentary: Oldest DNA sequences may reveal secrets of ancient animal ancestors, University of Warwick (+Newswise), 28 Oct 2015.
4 Sep 2015: ...Thousands of transcripts ...which are likely to have originated de novo.... NEW 4 Jan 2016.
Rafik Tarek Neme Garrido, "Evolutionary analyses of orphan genes in mouse lineages in the context of de novo gene birth," doctoral dissertation, Christian-Albrechts-Universität zu Kiel, Plön, Apr 2013.
Nathaniel Comfort, "Genetics: We are the 98%," three book reviews [link], doi:10.1038/520615a, p 615-616 v 520, Nature, 30 Apr 2015.
Christian Schlötterer, "Genes from scratch — the evolutionary fate of de novo genes" [Open Access abstract], doi:10.1016/j.tig.2015.02.007, Trends in Genetics, 14 Mar 2015.
8 Oct 2014: 24 hominoid-specific de novo protein-coding genes were identified.
26 Sep 2014: 23,849 anthropoid-specific constrained (ASC) regions with "robust functional signatures"
Cristina Sisu, Baikang Pei, Jing Leng, Adam Frankish, Yan Zhang et al., "Comparative analysis of pseudogenes across three phyla" [abstract], doi:10.1073/pnas.1407293111, Proc. Natl. Acad. Sci. USA, online 25 Aug 2014. "...Pseudogenes across the three phyla have a consistent level of partial activity, with ~15% being transcribed."
Rands CM, Meader S, Ponting CP, Lunter G, "8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage" [html], doi:10.1371/journal.pgen.1004525, 10(7): e1004525, PLoS Genet, 24 Jul 2014.
Palazzo AF, Gregory TR, "The Case for Junk DNA" [html], doi:10.1371/journal.pgen.1004351, 10(5): e1004351, PLoS Genet, 8 May 2014.
Li Zhao et al., "Origin and Spread of de Novo Genes in Drosophila melanogaster Populations" [abstract], doi:10.1126/science.1248286, p 769-772 v 343, Science, 14 Feb 2014.
24 Jan 2014: The earliest steps in de novo gene origination remain mysterious.
Sara C. Cloutier, Siwen Wang et al., "Long Noncoding RNAs Promote Transcriptional Poising of Inducible Genes" [html], doi:10.1371/journal.pbio.1001715, 11(11): e1001715, PLoS Biol, 19 Nov 2013.
György Abrusán, "Integration of New Genes into Cellular Networks, and Their Structural Maturation" [abstract], doi:10.1534/genetics.113.152256, Genetics, online 20 Sep 2013.
Reinhardt JA, Wanjiru BM, Brant AT, Saelao P, Begun DJ, et al., "De Novo ORFs in Drosophila Are Important to Organismal Fitness and Evolved Rapidly from Previously Non-coding Sequences" [html], doi:10.1371/journal.pgen.1003860, 9(10): e1003860, PLoS Genet, 17 Oct 2013.
Mary Anne T. Rubio et al., "Unusual Noncanonical Intron Editing Is Important for tRNA Splicing in Trypanosoma brucei" [abstract], doi:10.1016/j.molcel.2013.08.042, Molecular Cell, online 3 Oct 2013; and commentary: How a 'Mistake' in a Single-Cell Organism Is Actually a Rewrite Essential to Life, Ohio State University via Newswise, 3 Oct 2013.
Bryan J. Venters and B. Franklin Pugh, "Genomic organization of human transcription initiation complexes" [html], doi:10.1038/nature12535, p 53-58 v 502, Nature, 3 Oct 2013; and commentary: Scientists Discover the Origins of Genomic "Dark Matter", Pennsylvania State University, 13 Sep 2013.
Aleksandra E Kornienk et al., "Gene regulation by the act of long non-coding RNA transcription" [html], doi:10.1186/1741-7007-11-59, n59 v11, BMC Biology, 30 May 2013; and commentary: When function isn't always 'function' for non-coding RNAs, Biome, 20 Jun 2013.
Matthew J. Hangauer et al., "Pervasive Transcription of the Human Genome Produces Thousands of Previously Unidentified Long Intergenic Noncoding RNAs" [html], doi:10.1371/journal.pgen.1003569, 9(6): e1003569, PLoS Genet, 20 Jun 2013.
Aleksandra E Kornienko et al., "Gene regulation by the act of long non-coding RNA transcription" [html], doi:10.1186/1741-7007-11-59, n59 v11, BMC Biology, 30 May 2013.
Ephraim Kenigsberg and Amos Tanay, "Drosophila Functional Elements Are Embedded in Structurally Constrained Sequences" [html], doi:10.1371/journal.pgen.1003512, 9(5): e1003512, PLoS Genet, 30 May 2013; and commentary:
James G. D. Prendergast and Colin A. Semple, "Side Effects: Substantial Non-Neutral Evolution Flanking Regulatory Sites" [html], doi:10.1371/journal.pgen.1003528, 9(5): e1003528, PLoS Genet, 30 May 2013.
David S. Lawrie et al., "Strong Purifying Selection at Synonymous Sites in D. melanogaster" [html], doi:10.1371/journal.pgen.1003527, 9(5): e1003527, PLoS Genet, 30 May 2013.
W. Ford Doolittle, "Is junk DNA bunk? A critique of ENCODE" [abstract], doi:10.1073/pnas.1221376110, Proc. Natl. Acad. Sci. USA, online 11 Mar 2013.
Diethard Tautz &: Tomislav Domazet-Lošo, "The evolutionary origin of orphan genes" [abstract], doi:10.1038/nrg3053, p692-702 v12, Nature Reviews Genetics, Oct 2011.
Anne-Ruxandra Carvunis et al., "Proto-genes and de novo gene birth" [abstract], doi:10.1038/nature11184, p370374 v487, Nature, 24 Jun 2012.
25 Jan 2013: Many of our genes have no obvious relatives or evolutionary history. So where did they come from? (Also cites two references above.)
Taewoo Ryu, Loqmane Seridi and Timothy Ravasi, "The evolution of ultraconserved elements with different phylogenetic origins" [abstract], doi:10.1186/1471-2148-12-236, n236 v12, BMC Evolutionary Biology, 5 Dec 2012.
Lucas D. Ward and Manolis Kellis, "Evidence of Abundant Purifying Selection in Humans for Recently Acquired Regulatory Functions" [abstract], doi:10.1126/science.1225057, p1675-1678 v337, Science, 28 Sep 2012.
6 Sep 2012: Almost 80% of the genome is biochemically active....
19 Nov 2011: Where do new genes come from?
Clark MB, Amaral PP, Schlesinger FJ, Dinger ME, Taft RJ, et al., "The Reality of Pervasive Transcription" [html], PLoS Biol 9(7): e1000625. doi:10.1371/journal.pbio.1000625, online12 Jul 2011.
Elena Sotillo and Andrei Thomas-Tikhonenko, "The long reach of noncoding RNAs" [abstract], doi:10.1038/ng.870, p616-617 v43, Nature Genetics, online 28 Jun 2011.
Tiffany Hung et al., "Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters" [abstract], doi:10.1038/ng.848, p621-629 v43, Nature Genetics, online 5 Jun 2011.
Leila Taher et al., "Genome-wide identification of conserved regulatory function in diverged sequences" [abstract], doi:10.1101/gr.119016.110, Genome Research, online 31 May 2011.
Elizabeth Pennisi, "Shining a Light on the Genome's 'Dark Matter'" [abstract], doi:10.1126/science.330.6011.1614, p1614 v330, Science, 17 Dec 2010.
23 Jul 2010: The cell, and indeed evolution, can dial up these microRNAs very flexibly in different cells to address various targets, and they only need one protein complex to come and do the job.
Research team finds important role for junk DNA by Kitta MacPherson, News at Princeton, 20 May 2010.
David Lomelin et al., "Human genetic variation recognizes functional elements in non-coding sequence" [abstract], doi:10.1101/gr.094151.109, p311-319 v 20, Genome Research, Mar 2010 (online 23 Dec 2009).
Tobias J.A.J. Heinen, Fabian Staubach et al., "Emergence of a New Gene from an Intergenic Region" [summary], doi:10.1016/j.cub.2009.07.049, p1527-1531 v19, Current Biology, 29 Sep 2009.
Gregory E. Sims comments by email, 21 Oct 2009.
Gregory E. Sims et al., "Whole-genome phylogeny of mammals: Evolutionary information in genic and nongenic regions" [abstract], doi:10.1073/pnas.0909377106, p17077-17082 v106, Proc. Natl. Acad. Sci. USA, 6 Oct 2009.
Ahmad M. Khalil, Mitchell Guttman, Eric S. Lander, John L. Rinn et al., "Many human large intergenic noncoding RNAs associate with chromatin-modifying complexes and affect gene expression" [Open Access abstract], doi:10.1073/pnas.0904715106, Proc. Natl. Acad. Sci. USA, online 1 Jul 2009.
Tim R. Mercer, Marcel E. Dinger and John S. Mattick, "Long non-coding RNAs: insights into functions" [abstract], doi:10.1038/nrg2521, p 155-159 v 10, Nature Reviews Genetics, Mar 2009. "In mammals and other eukaryotes most of the genome is transcribed in a developmentally regulated manner...."
Stephen C. J. Parker et al., "Local DNA Topography Correlates with Functional Noncoding Regions of the Human Genome" [abstract], doi:10.1126/science.1169050, Science, online 12 Mar 2009. "These results support that the molecular shape of DNA is under selection...." Also see commentary, There's more to life than sequences by Phillip Ball, doi:10.1038/news.2009.160, Nature News, 12 Mar 2009.
Mitchell Guttman et al., "Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals" [abstract], doi:10.1038/nature07672, Nature, online 1 Feb 2009. Also see commentary: Scientists Uncover New Class of Non-Protein Coding Genes in Mammals with Key Functions, Broad Institute, 1 Feb, and Harvard, 2 Feb 2009.
Anton A. Turanov et al., "Genetic Code Supports Targeted Insertion of Two Amino Acids by One Codon" [abstract], doi:10.1126/science.1164748, p 259-261 v 323, Science, 9 Jan 2009. "...The choice of the inserted amino acid [is] determined by a specific 3' untranslated region structure and location of the dual-function codon within the messenger RNA." Also see commentary: Genetic Code Sees Double, by Haley Stephenson, ScienceNOW Daily News, 8 Jan 2009.
Rajkumar Sasidharan and Mark Gerstein, "Protein fossils live on as RNA" [html], doi:10.1038/453729a, p 729-731 v 453, Nature, 5 Jun 2008. "...Pseudogenes might not be purely dead relics of past genes but could be resurrected for new biochemical activities."
Aristotelis Tsirigos and Isidore Rigoutsos, "Human and mouse introns are linked to the same processes and functions through each genome's most frequent non-conserved motifs" [html], doi:10.1093/nar/gkn155, Nucleic Acids Research, online 1 May 2008. "The findings show that intronic regions from different genomes are linked to the same processes and functions in the absence of underlying sequence conservation."
Paulo P. Amaral et al., "The Eukaryotic Genome as an RNA Machine" [abstract], doi:10.1126/science.1155472, p 1787-1789 v 319, Science, 28 Mar 2008. "...The genomes of all studied eukaryotes are almost entirely transcribed, generating an enormous number of non–protein-coding RNAs (ncRNAs)."
Thomas R. Gingeras, "Origin of phenotypes: Genes and transcripts" [Open Access abstract], ISSN 1088-9051/07, p 682-690 v 17, Genome Research, Jun 2007. "...The unanticipated, but unanimous conclusion that there was a significantly greater amount of transcriptional output from genomes than could be accounted for by our current collection of annotated protein-coding transcripts."
Craig B. Lowe, Gill Bejerano and David Haussler, "Thousands of human mobile element fragments undergo strong purifying selection near developmental genes" [abstract], 10.1073/pnas.0611223104, Proc. Natl. Acad. Sci. USA, online 26 Apr 2007.
Xiaohui Xie et al., "Systematic discovery of regulatory motifs in conserved regions of the human genome, including thousands of CTCF insulator sites" [Open Access abstract], 10.1073/pnas.0701811104, Proc. Natl. Acad. Sci. USA, online 18 Apr 2007.
Matthew J. Oliver et al., "The mode and tempo of genome size evolution in eukaryotes" [abstract], 10.1101/gr.6096207, Genome Research, online 9 Apr 2007. "This model explains the skewed distribution of eukaryotic genome sizes without invoking strong selection against large genomes."
Hiroshi Kikuta et al., "Genomic regulatory blocks encompass multiple neighboring genes and maintain conserved synteny in vertebrates" [abstract], 10.1101/gr.6086307, Genome Research, online 26 Mar 2007.
Amos Tanay et al., "Hyperconserved CpG domains underlie Polycomb-binding sites" [abstract], 10.1073/pnas.0609746104, Proc. Natl. Acad. Sci. USA, online 21 Mar 2007.
Tanya Vavouri et al., "Parallel evolution of conserved non-coding elements that target a common set of developmental regulatory genes from worms to humans" [text], 10.1186/gb-2007-8-2-r15, Genome Biology, 2 Feb 2007.
Brian C. Thomas et al., "Arabidopsis intragenomic conserved noncoding sequence" [abstract], 10.1073/pnas.0611574104, p 3348-3353 v 104, Proc. Natl. Acad. Sci. USA, 27 (online 14) Feb 2007.
Shalev Itzkovitz and Uri Alon, "The genetic code is nearly optimal for allowing additional information within protein-coding sequences" [Open Access abstract], 10.1101/gr.5987307, p 405-412 v 17, Genome Research, Apr (online 9 Feb) 2007. Also see commentary by Tobias Bollenbach et al., "Evolution and multilevel optimization of the genetic code" [abstract], 10.1101/gr.6144007, p 401-404 v 17, Genome Research, online 9 Mar 2007.
Scientists Discover Parallel Codes In Genes,, 9 Feb 2007.
David Forest et al., "RNA expression in a cartilaginous fish cell line reveals ancient 3' noncoding regions highly conserved in vertebrates" [abstract], 10.1073/pnas.0610350104, Proc. Natl. Acad. Sci. USA, online 16 Jan 2007.
Byrappa Venkatesh et al., "Ancient Noncoding Elements Conserved in the Human Genome" [abstract], 10.1126/science.1130708, p 1892 v 314, Science, 22 Dec 2006.
Len A. Pennacchio et al., "In vivo enhancer analysis of human conserved non-coding sequences" [text], 10.1038/nature05295, p 499-502 v 444, Nature, 23 Nov 2006.
Shyam Prabhakar, James P. Noonan et al., "Accelerated Evolution of Conserved Noncoding Sequences in Humans" [abstract], 10.1126/science.1130738, p 786 v 314, Science, 3 Nov 2006.
Looking for Smarts Between the Genes, by Michael Balter, ScienceNOW Daily News, 3 Nov 2006. "The strongest evidence for accelerated evolution on the human line was found in noncoding sequences next to genes involved in helping neurons adhere to each other."
6 Oct 2006: Once dismissed ...'jumping genes' are now regarded as major players ....
15 Jun 2006: Novel genes derived from noncoding DNA have been identified....
Isidore Rigoutsos et al., "Short blocks from the noncoding parts of the human genome have instances within nearly all known genes and relate to biological processes" [abstract | Open Access pdf], 10.1073/pnas.0601688103, p 6605-6610 v 103, Proc. Natl. Acad. Sci. USA, 25 Apr 2006.
Alison P. Lee et al., "Highly conserved syntenic blocks at the vertebrate Hox loci and conserved regulatory elements within and outside Hox gene clusters" [abstract], 10.1073/pnas.0601492103, Proc. Natl. Acad. Sci. USA, online 24 Apr 2006.
Gayle K. McEwen et al., "Ancient duplicated conserved noncoding elements in vertebrates: A genomic and functional analysis" [abstract], 10.1101/gr.4143406, p 451-465 v 16, Genome Research, April (online 13 Mar) 2006.
Michael Kamal et al., "A large family of ancient repeat elements in the human genome is under strong selection" [abstract / Open Access pdf], 10.1073/pnas.0511238103, Proc. Natl. Acad. Sci. USA, online 13 Feb 2006.
Where 'jumping genes' fear to tread, EurekAlert!, 4 Jan 2006. "Transposons comprise an estimated 45% of the total DNA content in the human genome. ...Dr. John Mattick's laboratory at the University of Queensland, Australia, identified long tracks of genomic segments (greater than 10 kilobases in length) that lack transposable elements. ...It appears that TFRs [Transposon-Free Regions] might be the passive signatures of one or more poorly understood mechanisms of gene regulation that operate in higher organisms, suggesting a wider role for noncoding sequences than has hitherto been appreciated."
Louisa Flintoft, "...An adaptive view of non-coding DNA" [text], doi:10.1038/nrg1756, p 880 v 6, Nature Reviews Genetics, Dec 2005.
UCSD Study Shows 'Junk' DNA Has Evolutionary Importance, by Kim McDonald, University of California, San Diego, 19 Oct 2005.
Peter D. Keightley et al., "Evolutionary constraints in conserved nongenic sequences of mammals" [abstract], doi: 10.1101/gr.3942005, p 1373-1378 v 15, Genome Research, Oct 2005.
Austen R. D. Ganley et al., "Identifying gene-independent noncoding functional elements in the yeast ribosomal DNA by phylogenetic footprinting" [abstract | Open Access PDF], doi: 10.1073/pnas.0504905102, p 1178711792 v 102, Proc. Natl. Acad. Sci. USA, 16 Aug (online 4 Aug) 2005.
Adam Siepel et al., "Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes" [abstract], Genome Research, doi: 10.1101/gr.3715005, online 15 Jul 2005.
Don't Call It Junk, by John Bohannon, ScienceNow, 14 Jul 2005.
Ekat Kritikou, "Non-coding transcripts — more than meets the eye" [abstract], p 347 v 6 n 5, Nature Reviews Genetics, May 2005.
N.G. Smith, M. Brandstrom and H. Ellegren, "Evidence for turnover of functional noncoding DNA in mammalian genome evolution" [abstract], p 806-813 v 84 n 5, Genomics, Nov 2004. "What proportion of the noncoding mammalian genome is functional? ...Measures of functional constraint based on human-mouse comparisons may seriously underestimate the true value.", owned and operated by Ryan Taft.
Marcello Nóbrega et al., "Megabase deletions of gene deserts result in viable mice" [abstract], p 988-993 v 431, Nature, 21 Oct 2004. "Some of the deleted sequences might encode for functions unidentified in our screen...."
3 June 2004: Knockout mice leave ultraconserved regions unexplained.
7 May 2004: Ultraconserved elements.
16 Apr 2004: The rat genome has been sequenced.
Tanita Casci, "Functional oases in genomic deserts" [text], p 930-931 v 4, Nature Reviews Genetics, Dec 2003.
2003, November 20: In mammals, CNGs are more numerous and better conserved than genes — our original announcement of this new page, with additional information.
Marcelo A. Nobrega et al., "Scanning Human Gene Deserts for Long-Range Enhancers" [pdf], p 413 v 302, Science, 17 Oct 2003.


1. Mark Johnston and Gary D. Stormo, "Heirlooms in the Attic" [
summary], p 997-999 v 302, Science, 7 Nov 2003.
2. Emmanouil T. Dermitzakis, Alexandre Reymond, Nathalie Scamuffa, Catherine Ucla, Ewen Kirkness, Colette Rossier and Stylianos E. Antonarakis, "Evolutionary Discrimination of Mammalian Conserved Non-Genic Sequences (CNGs)" [abstract], p 1033-1035 v 302, Science, 7 Nov 2003.
3. Emmanouil T. Dermitzakis, Alexandre Reymond, Robert Lyle, Nathalie Scamuffa, Catherine Ucla, Samuel Deutsch, Brian J. Stevenson, Volker Flegel, Philipp Bucher, C. Victor Jongeneel and Stylianos E. Antonarakis, "Numerous potentially functional but non-genic conserved sequences on human chromosome 21" [abstract], p 578-582 v 420, Nature, 5 Dec 2002. (See Supplement.)
4. Tom Ray and Brig Klyce, "New genetic programs in Darwinism and strong panspermia" [on this website], 7 Apr 2002.
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