20 November 2003: 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

It was already known that there were 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).

Implications

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

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, ScienceDaily.com, 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 ....
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 ...now 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 11787–11792 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."
NoncodongDNA.com, 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.

References

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.