last updated May 21, 2001

from GodAndScience Website

The existence of large amounts of non-coding DNA (up to 97% in humans) in the genomes of eukaryotes has been used as an argument against intelligent design (and the role of a Creator) and as an argument for the random process of evolution ⁽¹⁾. Two evolutionary theories attempted to explain the reason for the existence of non-coding DNA.

One theory stated that non-coding DNA was "junk" that consisted of randomly-produced sequences that had lost their coding ability or partially duplicated genes that were non-functional. The second theory stated that non-coding DNA was "selfish", in that it consisted of DNA that preferentially replicated more efficiently that coding DNA, even though it provided no selective advantage (in fact was somewhat detrimental since it was parasitic).

There have always been problems with these arguments, which have been ignored by many of those making these claims.

The main question presented by proponents of the "junk" or "selfish" DNA theories is,

"Why would a perfect God create flawed DNA which is primarily composed of useless, non-coding regions?"

The definitive answer has finally arrived, although for many years there have been strong suggestions of what the non-coding DNA is doing in our genomes.

Crytomonad

flagellated single-celled photosynthetic organism
 

A recent study has shown that eukaryotic non-coding DNA (also called "secondary DNA) is functional as a structural element in the nucleus.

The new study examined the genomes of the single-celled photosynthetic organisms know as Crytomonads. These organisms exist as vastly different cell sizes, with the nucleus being proportional in size to that of the cell. Researchers discovered that the amount of non-coding DNA was proportional to the size of the nucleus, suggesting that more non-coding DNA was structurally required in larger nuclei.

As an added proof, the nucleomorph, a small piece of DNA contained within the plastid that codes for itself and photosynthetic function, was not changed in size, despite changes in cell size and nuclear content. The new study is a stunning rebuttal to the evolutionary theories that attempt to discredit design and promote concepts such as "junk" DNA and "selfish" DNA.

The conclusion according to the authors is quoted below:

"Furthermore, the present lack of significant amounts of nucleomorph secondary DNA confirms that selection can readily eliminate functionless nuclear DNA, refuting 'selfish' and 'junk' theories of secondary DNA".

(see Beaton, M.J. and T. Cavalier-Smith. 1999. Eukaryotic non-coding DNA is functional: evidence from the differential scaling of cryptomonal genomes. Proc. R. Soc. Lond. B. 266:2053-2059.)

The answers to the question of "junk" DNA have been coming in for years, and we now know that the "junk" is not really junk.

Since "junk" DNA is not really junk, from now on I will call it "non-coding" DNA. Let's first look at some of the early studies which indicated that there was some design behind the non-coding DNA. Initial and subsequent studies showed there were long areas of non-coding DNA which contained palindromes, thus maintaining symmetry between complementary strands ⁽²⁾.

Other studies, examining large regions of genomes, using statistical techniques borrowed from linguistics, have shown patterns in the non-coding DNA similar to that seen in human languages ⁽³⁾.

For example, when you take human language texts and create a histogram plotting the log of the frequency of occurrence of words against the log of the rank, the resulting plot is always linear with a slope of -1 for every human language. Likewise, when you perform the same plot for coding and non-coding DNA, the plot for the non-coding DNA exhibits a nearly perfect linear relationship (much better than that seen for the coding regions of DNA).

The purpose or function of this "DNA language" was not determined. Another study showed that DNA contains large areas with unexplained patterns ⁽⁴⁾.

Such patterns could not be the result of random chance as stated by Dr. H. Eugene Stanley (Boston University),

"it is almost incredible that the occupant of one site on a gene would somehow influence which nucleotide shows up even 100,000 bases away."

Scientists have noticed for some time that eukaryotic genomes consist of large amounts of transposable and interspersed repetitive elements (TIREs).

A study of insect TIREs showed that the Lepidopteran Bombyx mori (the silkmoth) exhibits the short interspersion pattern in which Alu-like TIREs predominate while Drosophila possesses the long interspersion pattern in which retroviral-like TIREs are prevalent.

An analysis of these sequences revealed highly non-random patterns of TIREs in both Bombyx and Drosophila. These patterns suggested that these sequences were under cellular regulation rather than useless or selfish junk DNA ⁽⁵⁾.

Later studies showed that simple, repetitive (gt)n(ga)m DNA sequences are present in major histocompatibility complex MHC-DRB genes for many distantly related animals, such as artiodactyla (large hoofed mammals) and man. Obviously, if these sequences were truly junk, they would not be expected to have been preserved through millions of years of evolution.

Gel retardation experiments revealed that these simple repetitive (gt)n(ga)m sequences bind nuclear proteins and show characteristics of a specific DNA-protein interaction ⁽⁶⁾. What functions these DNA-protein interactions exhibit has not been determined. However, there are many other examples of DNA-protein interaction which exhibit regulatory control of DNA transcription.

Other studies have demonstrated the remarkable similarity of sequence homology in the T-cell receptor genes of mice and men.

Scientists compared the DNA sequence of nearly 100 kilobases of contiguous DNA in the C delta to C alpha region of the alpha/delta T-cell receptor loci (TCRAC/TCRDC) of mouse and man. This analysis, the largest genomic sequence comparison so far, identified a very high level of organizational and noncoding sequence similarity (approximately 71%).

The authors conclude,

"This observation begins to question the notion that much of the chromosomal non-coding sequence is junk ⁽⁷⁾."

More definitive studies have shown that non-coding DNA provides structure to DNA so that it can perform many functions which would be impossible without some form of structure.

One of the readily apparent differences between prokaryotic and eukaryotic DNA is that eukaryotic DNA is organized into chromosomes, which is further organized into chromatin code. This kind of structure does not "just happen" for DNA - it requires specific design. The coding regions of DNA are concentrated in the chromosomal regions which are the richest in G (guanine) and C (cytosine) and seem to correspond to the telomeric regions of certain chromosome arms (T-bands) ⁽⁸⁾.

Scientists have genetically modified and therefore removed a single telomere of one chromosome in yeast cells ⁽⁹⁾.

The elimination of the telomere caused cell cycle arrest (stopping of cell division), indicating that telomeres help cells to distinguish intact chromosomes from damaged DNA. In the cells that recovered from the arrest the chromosome was eventually lost, demonstrating that telomeres are essential for maintaining chromosome stability.

Therefore, non-coding DNA is absolutely necessary for chromosomal structure and function.

Studies published in February, 1997, show that organisms produce special proteins that bind to the telomeres during DNA replication ⁽¹⁰⁾. These proteins are counted in order to determine how long the telomeric DNA should be, otherwise the telomere would be shortened with each replication, eventually resulting in loss of critical genes.

As you learned in high school, the chromosomes are replicated and segregated during mitosis (cell division). Complex interactions occur between the centromeres of chromosomes and the spindles to which they attach. These centromeres form an integrated protein/DNA complex, which is required for chromosomal movement during mitosis ⁽¹¹⁾.

What you may not have learned is that the metaphase chromosomes are dynamically modified in interphase. In interphase nuclei, orderly transcription and replication involve highly folded chromosomal domains containing hundreds of kilobases of DNA.

Specific non-coding DNA sequences within selected chromosome domains participate in more complex levels of chromosome folding, and index different genetic compartments for orderly transcription and replication.

There is also evidence that three-dimensional chromosome positions within the nucleus contribute to phenotypic expression. Entire chromosomes are maintained as discrete, reasonably compact entities in the nucleus, and heterochromatic coiled domains of several thousand kilobases can acquire unique three-dimensional positions in differentiated cell types. This unique structure controls the expression of specific genes in cells of differentiated cell types ⁽¹²⁾.

Therefore, non-coding DNA is essential for differential gene expression seen in the differentiated cell types seen throughout eukaryotic organisms.

Recent advances have demonstrated that non-protein-coding DNA provides the structural basis of the metaphase chromosomal banding pattern. CpG islands, DNA loops, and matrix attachment sites form the basis of G versus R banding patterns, revealing how non-coding DNA forms the basis of chromosomal structure ⁽¹³⁾.

Another study, examining a 2.84 Mb section of the human genome, showed that microsatellites, tandem repeat sequences abundant in the genomes of higher eukaryotes, contain reiterating A-rich loci, which are involved in the higher-order organization of the chromatin ⁽¹⁴⁾.

Other studies have shown satellites consisting of about 1 million copies of a 221-bp tandem repeat unit has been localized in the centromeres of 58 of the 64 horse chromosomes ⁽¹⁵⁾. Many hundreds of studies have implicated mutations in satellites, mini-satellites, and microsatellites, in diseases which show genetic linkage, including studies on Crohn's disease, of which I have been part of.

It appears that heterochromatin, composed of what was once thought to be junk DNA, may have some role in suppression of gene(s) and/or spreading of inactivation, if genes are embedded within the heterochromatic region ⁽¹⁶⁾.

In a recent study, investigators examined, through genetic engineering, the relationship between exon (protein coding DNA) and intron (non-coding DNA) size in pre-mRNA (messenger RNA, from which protein translation is accomplished) processing. Exons were placed in vertebrate genes along with small and large introns.

Both exon and intron size influenced splicing phenotype, such that when introns were large, large exons were skipped; when introns were small, the same large exons were included. These results indicated that non-coding introns can control the recognition and transcription of exons (protein-coding DNA) (17). In addition, introns encoded within transfer RNA (tRNA) genes, which recognize the genetic code on mRNA, code for their splicing, which allow them to recognize amino acids during the protein translation process ⁽¹⁸⁾.

There is growing evidence that noncoding DNA plays a vital role in the regulation of gene expression during development ⁽¹⁹⁾. These studies demonstrate that non-coding DNA regulates development of photoreceptor cells ⁽²⁰⁾, the reproductive tract ⁽²¹⁾, and the central nervous system ⁽²²⁾.

Therefore, non-coding DNA regulates the vital roles of development and embriogenesis.

Some of the non-coding DNA provides proper framing for translation of proteins. The DNA is, of course, a triplet code, with each triplet coding for the placement of one amino acid. In order to be read properly, the reading frame must be properly established. If the reading frame were shifted by one or two positions in either direction, the resulting protein would be completely different and would be "junk" protein. Therefore, the translation framing code is responsible for correct triplet counting by the ribosome during protein synthesis ⁽²³⁾.

A recent study has shown that genes (as many as five at a time) are found within the introns of other genes ⁽²⁴⁾.

This kind of arrangement results in the simultaneous expression of all of these genes during transcription of the gene in question. Such regulatory control is rather remarkable, suggesting intelligent designed as opposed to random chance. Some of the non-coding DNA is loop code for single-stranded RNA-protein interactions.

The codes are degenerate and corresponding messages are not only interspersed but actually overlap, so that some nucleotides belong to several messages simultaneously. Tandemly repeated sequences frequently considered as functionless "junk" are found to be grouped into certain classes of repeat unit lengths, indicating functional involvement of these sequences.

It is likely these tandem repeats play the role of weak enhancer-silencers that modulate, in a copy number-dependent way, the expression of proximal genes.

Well over 700 studies (over 100 in the last year) have demonstrated the role of non-coding DNA as enhancers for transcription of proximal genes. These intronic enhancers have been described for:

• eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) ⁽²⁵⁾

• the variable region of the rearranged immunoglobulin mu (IgM) gene ⁽²⁶⁾

• the alpha-globin gene ⁽²⁷⁾

• the activin beta A subunit gene ⁽²⁸⁾

• lambda 2 light chain transgenes ⁽²⁹⁾

• Human CYP1B1, a member of the cytochrome P450 superfamily ⁽³⁰⁾

• immunoglobulin heavy chain (IgH) ⁽³¹⁾

• alcohol dehydrogenase ⁽³²⁾

• 3 alpha-hydroxysteroid dehydrogenases ⁽³³⁾

• apolipoprotein A-II ⁽³⁴⁾

• beta1,4-N-acetylgalactosaminyltransferase ⁽³⁵⁾

• kappa light chain gene ⁽³⁶⁾

• Alpha-1 acid glycoprotein ⁽³⁷⁾

• the T-cell receptor beta-chain ⁽³⁸⁾

• 2-crystallin ⁽³⁹⁾

• 1 tubulin gene ⁽⁴⁰⁾

• aldolase B gene ⁽⁴¹⁾

• and many others...

Another 60+ studies have demonstrated the role of non-coding DNA as silencers for suppression of transcription of proximal genes.

The presence of silencer genes has been shown to down-regulate:

• the apolipoprotein A-II gene ⁽⁴²⁾

• the osteocalcin gene ⁽⁴³⁾

• the 2-crystallin gene ⁽⁴⁴⁾

• the CD4 gene ⁽⁴⁵⁾

• the beta globin gene ⁽⁴⁶⁾

• the gene for the neuron-glia cell adhesion molecule, Ng-CAM ⁽⁴⁷⁾

• the renin gene ⁽⁴⁸⁾

• the keratin 18 gene ⁽⁴⁹⁾

• the platelet-derived growth factor A-chain gene ⁽⁵⁰⁾

• and dozens of other genes...

In addition, there are 3' and 5' untranslated regions (UTR) which regulate translation of proteins. Certain trans-acting binding proteins bind to the 3' and 5' UTRs of proximal and distal genes to regulate their translation.

This non-coding DNA has been shown to regulate:

• the Lipoprotein Lipase gene ⁽⁵¹⁾

• the glucose transporter gene ⁽⁵²⁾

• coxsackie B3 virus ⁽⁵³⁾

• the bax-alpha gene ⁽⁵⁴⁾

• glutathione peroxidase and phospholipid-hydroperoxide glutathione peroxidase genes ⁽⁵⁵⁾

• the FMR1 gene ⁽⁵⁶⁾

• the c-mos gene ⁽⁵⁷⁾

• the luteinizing hormone/human chorionic gonadotropin receptor gene ⁽⁵⁸⁾

• the thyrotropin receptor gene ⁽⁵⁹⁾

• the beta-globin gene ⁽⁶⁰⁾

• the interleukin 1 type I receptor gene ⁽⁶¹⁾

• the translation initiation factor eIF-2 alpha gene ⁽⁶²⁾

• the N-methyl-D-aspartate receptor NR2A subunit gene ⁽⁶³⁾

• the catalase gene ⁽⁶⁴⁾.

In addition, 3'UTRs have been shown to down-regulate translation of maternal mRNA in oocytes ⁽⁶⁵⁾, therefore playing a role in embriogenesis and development.

Another role for the 3' and 5' UTR is to regulate the rate of mRNA decay, which has now been shown to be a precise process dependent on a variety of specific cis-acting sequences and trans-acting factors ⁽⁶⁶⁾.

The roles of non-coding DNA are so numerous and pervasive that evolutionary studies are now looking at these sequences for patterns of "concerted evolution ⁽⁶⁷⁾." In summary, the non-coding DNA, contrary to statements by evolutionists, is not useless, but is, in fact, required for genomic functionality, therefore providing evidence of intelligent design.

The "junk" DNA is really some rather amazing "junk."

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