Functional versus Junk DNA Predictions

...there exists a misconception among functional genomicists that the evolutionary process can produce a genome that is mostly functional.²⁵

If the human genome is indeed devoid of junk DNA as implied by the ENCODE project, then a long, undirected evolutionary process cannot explain the human genome.²⁶

We would expect that natural selection would be powerless to stop the accumulation of certain genomic alterations over the entirety of metazoan [meaning animal] evolution.²⁸

The mutational load would be too great to allow survival if all the DNA of most eukaryotes carry was composed of essential genes [...]

Taking into consideration this frequency of spontaneous mutations and the maximal mutational load, Muller estimated the number of functioning gene loci in mammals to be approximately 3 x 10⁴, or about 1% of the genome [...]

Even if the estimate of 3 x 10⁴ is off by a factor of 10, this would still account for only 10% of the genome. ⁴

The moment we acquire 10⁵ gene loci, the overall deleterious mutation rate per generation becomes 1.0 which appears to represent an unbearably heavy genetic load [...] Even if an allowance is made for the existence in multiplicates of certain genes, it is still concluded that at the most, only 6% of our DNA base sequences is utilized as genes⁵

A second widely used argument which suggests a minimum of informational DNA in the eukaryote genome (less than 10% of the available DNA) states that the mutational genetic load would be inordinate if mammals used all their DNA to carry and transmit biological information... If one accepts that the majority of gene substitutions and polymorphisms are selectively neutral, then the restrictions imposed by a genetic load on functional gene number become negligible. Neutral gene substitutions certainly cannot contribute to any accumulating substitutional or mutational load which depends upon selective disadvantage for its action. We must therefore estimate whether the number of functional genes are minimal, or rather that most gene substitutions are inconsequential with respect to natural selection.⁶

In other words, because of genetic load then either the genome must have very few genes, or the genes must be mostly made of junk DNA that can mutate without consequence.  He goes on to promote the latter hypothesis.

Middle-repetitive DNAs together comprise too large a fraction of most eukaryotic genomes to be kept accurate by Darwinian selection operating on organismal phenotype.⁷

If much of the DNA is simply “spacer” DNA whose sequence is irrelevant, then there will be a far smaller mutational load. But notice that the sequence must be truly irrelevant, not just of unknown function... Thus the mutational load argument seems to give weight to the notion that this DNA is nonspecific in sequence.¹⁵

Thus, according to the ENCODE Consortium, a biological function can be maintained indefinitely without selection, which implies that at least 80 – 10 = 70% of the genome is perfectly invulnerable to deleterious mutations, either because no mutation can ever occur in these “functional” regions, or because no mutation in these regions can ever be deleterious. This absurd conclusion was reached through various means [...] only sequences that can be shown to be under selection can be claimed with any degree of confidence to be functional... The absurd alternative... is to assume that no deleterious mutations can ever occur in the regions they have deemed to be functional.²⁵

If the human genome is indeed devoid of junk DNA as implied by the ENCODE project, then a long, undirected evolutionary process cannot explain the human genome... If ENCODE is right, evolution is wrong.²⁶

If the rate at which these mutations are generated is higher than the rate at which natural selection can weed them out, then the collective genomes of the organisms in the species will suffer a meltdown as the total number of deleterious alleles increases with each generation... [This is] incompatible with the view that 80% of the genome is functional in the sense implied by ENCODE.²⁸

It should be no more than 1 or 2 deleterious mutations per generation [...] If the deleterious mutation rate is too high, the species will go extinct.³⁶

There is an upper bound to the number of genes we can possibly carry, and it happens to be in the neighborhood of the number of genes estimated in the human genome project [...] this is why some of us go all spluttery and cross-eyed at any mention of the ENCODE project. They just blithely postulated orders of magnitude more functioning elements in the genome than could be tolerated by any calculation of the genetic load.²⁰

Most people in the field [of theoretical genetics] think the human genome is clearly degenerating, but they dismiss this as merely arising due to relaxed selection. But those who have examined it most closely realize that even with intense selection there is still a profound problem.³⁹

It is inevitable that natural selection of the special sort we call non-phenotypic will favor the development within genomes of DNAs whose only "function" is survival within genomes.⁷

John Maynard Smith, a population geneticist from the University of Sussex, England, cut through what confusion remained with this clear statement: "If there are elements in the genome that can multiply, and if certain structures of these elements can influence their replication, then it follows logically that there will selfish DNA."

To quote Dawkins: "The true 'purpose' of DNA is to survive, no more and no less. The simplest way to explain the surplus DNA is to suppose that it is a parasite or at best a harmless but useless passenger, hitching a ride in the survival machines created by the other DNA."¹³

the molecular processes generating extra DNA outpace those getting rid of it.¹⁴

[Mobile elements] have come to be present in such great abundance because they have found mechanistic ways to proliferate within host genomes.²⁴

the vast majority of transposons in the human genome are merely parasites, parasites of parasites, and dead parasites.²⁵

In fact, the genome resembles nothing so much as a hodgepodge of borrowed, copied, mutated, and discarded sequences and commands that has been cobbled together by millions of years of trial and error against the relentless test of survival.¹¹

The most striking feature of the genomic analyses we now have is how much apparently nonfunctional DNA there is. Birds have it, bees have it, we have it, but some simpler organisms, bacteria, for example, have far less of it. The genomes of multicellular organisms are full of what look like the residues of sequences that were once functional genes, often in many copies, but that have now become degraded and lay no role in generating proteins...

From the Darwinian perspective all this is explicable--the molecular equivalent of the tinkering that is pervasive in the history of life at the anatomical level.¹⁸

The tinkerer [of evolution] […] manages with odds and ends. What he ultimately produces is generally related to no special project, and it results from a series of contingent events, of all the opportunities he had to enrich his stock with leftovers."²⁵

It seems totally implausible that the number of radically different genes needed in a salamander is 20 times that in a man.⁸

The DNA instructions for making a human being comprise some 4 billion nucleotide pairs, while those for a one-celled amoeba contain 300 billion nucleotide pairs. There is little evidence that amoebae are almost a hundred times more "advanced" than humans"¹⁰

Dr. Venter pointed out that there is a good excuse for those who have long shrugged off junk as so much garbage. After all, some organisms function just fine without it. The smallpox virus, the E. coli bacterium and other microorganisms have only genes packed shoulder to shoulder, with no junk or introns in between. Even a couple of higher creatures, like the puffer fish, have very little noncoding DNA.¹²

Less than 5 percent of the human DNA has a coding function. Salamanders do much better--or worse, depending on one’s point of view. Some of these animals have twenty times more DNA than we have, with those in the west of the United States beating those in the east by severalfold.¹³

Why does an onion need a genome that is about five times larger than ours?"²⁵

A human genome contains eight times more DNA than that of a pufferfish but is 40 times smaller than that of a lungfish.²⁸

The eukaryotic genome is amde mostly of noncoding DNA without obvious function, sometimes called "junk" or "ballast" DNA. Less than 5 percent of the human DNA has a coding function...

The amount of apparently useless DNA in the genome of higher plants and animals requires an explanation...

On the other hand, the possibility that this DNA plays a role, for example, in chromosomal structure, or in some other unknown way, cannot be excluded.¹³

Rather than being intelligently designed, the human genome looks more and more like a mosaic of mutations, fragment copies, borrowed sequences, and discarded strings of DNA that were jerry-built over millions of years of evolution.¹⁷

Go for the gusto andask them what their god was thinking when he loaded up your genome with the molecular equivalent of styrofoam packing peanuts¹⁹

The majority of human DNA consists of repetitive, mutationally degraded sequences.²⁸

it is known from several species groups that chromosome arms increase proportionally in length as species accumulate more DNA, e.g. in salamanders. This might be a reflection of some process [...] that requires that certain regions of the genome should be kept as separable unique entities [...] we should not abandon all hope of arriving at an understanding of the manner in which some sequences might affect the biology of organisms in completely novel and somewhat unconventional ways.⁴²

Maynard Smith said that the selfish or ignorant origin of DNA does not necessarily imply that it has no effect on its host. Some sequences might became involved in signaling, and all of them, simply by increasing the amount of DNA in the nucleus, might influence the size and cycle time of the host cells.⁹

While a Creation/Fall model could account for the accumulation of some random, mutationally defective "extra copies," evolutionists felt they had a strong point that 97% "junk" DNA pointed more to evolution than intelligent design. Creationists have long suspected that this "junk DNA" will turn out to have a function. In fact, junk DNA research is now a hot topic; not only are more and more functions being detected, but it is suspected that junk DNA is full of yet-to-be-discovered "intellectual riches."⁴⁶

A do-nothing string of NOPs [no operations] might appear as "junk code" to the uninitiated, but, when inserted in a program loop, a string of NOPs can be used to achieve a precise time delay. Perhaps the "junk DNA" puzzle would be solved more rapidly if a few more computer scientists would make the switch to molecular biology.⁴⁸

because we have not yet discovered a use for a structure does not mean that no use exists⁴⁹

Little by little, the so-called "junk" DNA is revealing its functions... It would be foolish indeed to pronounce anything as "junk." Like the "vestigial organs" idea, it seems that evolutionary ideas about the molecular machines in cells feed on lack of knowledge.⁵⁰

On an evolutionary view we expect a lot of useless DNA. If, on the other hand, organisms are designed, we expect DNA, as much as possible, to exhibit function.⁵¹

A theory of design can in principle be predictive and quantitative [...] The good-design assumption leads to specific predictions and applications, e.g., the prediction that it is unlikely to find wires which take up metal and space but serve no purpose, with the application that studying any particular wire is likely to be useful. A bad-design assumption (e.g. that the chip maker made many random circuits and then just picked out the ones that worked) would give very different predictions.⁵²

"Junk DNA" (or, rather, DNA that doesn’t directly code for proteins) is not evidence for evolution. Rather, its alleged junkiness is a deduction from the false assumption of evolution. Just because no function is known, it doesn’t mean there is no function.⁵³

We have to wonder why the Intelligent Designer added to our genome junk DNA, repeated copies of useless DNA, orphan genes, gene fragments, tandem repeats, and pseudo­genes, none of which are involved directly in the making of a human being.¹⁷

What rival explanation can creationist provide? They can't say these are strikingly good designs. For much of what we find is a disorderly botch, some if it dangerous and needing newly contrived methods of control. As the evidence accumulates, creationists increasingly must take refuge in responses Darwin saw as unsatisfactory evasions, appealing to the thought that these properties of life are unfathomable mysteries.¹⁸

Much of our makeup is entirely by accident, and evolution is a story of filtered accidents. Creationists don’t like that — one of their central assumptions is that everything is purposeful — but don’t pander to their beliefs. Go for the gusto and ask them what their god was thinking when he loaded up your genome with the molecular equivalent of styrofoam packing peanuts¹⁹

Turning the genome into a well oiled efficient machine in which every last nucleotide has a function is the dream of every creationist and IDiot (derogatory term for intelligent design proponent), so the frequent killing of junk DNA serves no good purpose.⁵⁴

If on the other hand organisms are designed, then all DNA, or as much as possible, is expected to exhibit function.²⁶

I have noticed that there are some creationists who are jumping on [the 2012 ENCODE results] because they think that's awkward for Darwinism.  Quite the contrary it's exactly what a Darwinist would hope for, is to find usefulness in the living world [...] we thought only a minority of the genome was doing something, mainly that minority which only codes for protein, and now we find that actually the majority of it is doing something.  What it's doing is calling into action the protein coding genes. [...] The program that's calling them into action is the rest that had previously been written off as junk.⁶¹

The thought before the start of the [ENCODE] project, was that only 5 to 10 percent of the DNA in a human being was actually being used. The big surprise was not only that almost all of the DNA is used but also that a large proportion of it is gene switches.⁶²

Where tested, these [differentially expressed] noncoding RNAs usually show evidence of biological function in different developmental and disease contexts, with, by our estimate, hundreds of validated cases already published and many more en route, which is a big enough subset to draw broader conclusions about the likely functionality of the rest.⁶⁴

While not everyone yet agrees with me, the evidence is very strong and my thesis is more widely accepted than it once was.⁶⁵

The term "junk DNA" repelled mainstream researchers from studying noncoding genetic material for many years.⁶⁷

"The math just doesn't add up...There's just not enough molecular diversity" in proteins to create the complexity of the brain. "For a while, I despaired of ever being able to even think about this in my lifetime in a rational way," Mehler says. Then he heard about noncoding RNA.⁶⁸

I consider that these publications [the 1980 papers advocating junk DNA by Doolittle, Sapienza, Crick, and Orgel] are bordering with crime [borderline-criminal] because they completely misled scientific community so that all the messages carrying by the noncodingsequences have been ignored since then--30 years.⁶⁹

These two papers inflicted an immense damage to biological sciences.⁶⁹

Intergenic DNA was dismissed as irrelevant junk and many transcripts are presumed to be just so much noise... Early gene therapytrials were, for example, halted owing to unforeseen knock-on consequences of gene insertion.⁷⁰