Junk No More

Casey Luskin September 5, 2012 4:08 PM | Permalink

A groundbreaking paper in Nature reports the results of the Encyclopedia of DNA Elements (ENCODE) project, which has detected evidence of function for the "vast majority" of the human genome. Titled "An integrated encyclopedia of DNA elements in the human genome," the paper finds an "unprecedented number of functional elements," where "a surprisingly large amount of the human genome" appears functional. Based upon current knowledge, the paper concludes that at least 80% of the human genome is now known to be functional:

The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation.

(The ENCODE Project Consortium, "An integrated encyclopedia of DNA elements in the human genome," Nature, Vol. 489:57-74 (September 6, 2012) (emphasis added))

In the past we've frequently read about studies reporting function for many thousands of base pairs (see here or here for a few of many examples), but it's often hard to get a sense of just how much of the genome has had function detected for it. Through the collaboration of hundreds of researchers, the ENCODE project determined that "The vast majority (80.4%) of the human genome participates in at least one biochemical RNA- and/or chromatin-associated event in at least one cell type."

"Surprisingly Large" Amount of the Human Genome is Functional

The ENCODE paper divides up functional genomic elements into major categories: RNA transcribed regions, protein-coding regions, transcription-factor-binding sites, chromatin structure, and DNA methylation sites. After analyzing all of these different kinds of genomic elements, the project found:

Accounting for all these elements, a surprisingly large amount of the human genome, 80.4%, is covered by at least one ENCODE-identified element. The broadest element class represents the different RNA types, covering 62% of the genome (although the majority is inside of introns or near genes). Regions highly enriched for histone modifications form the next largest class (56.1%). Excluding RNA elements and broad histone elements, 44.2% of the genome is covered. Smaller proportions of the genome are occupied by regions of open chromatin (15.2%) or sites of transcription factor binding (8.1%), with 19.4% covered by at least one DHS or transcription factor ChIP-seq peak across all cell lines. (internal citations removed)

In addition to finding 863 pseudogenes that are "transcribed and associated with active chromatin," the paper reports that nearly all of the genome is found near a functional DNA element: "A total of 99% of the known bases in the genome are within 1.7 kb of any ENCODE element."

"Non-Conserved" No Longer Implies "Non-Functional"

As we've discussed here on ENV before, molecular biologists often infer function for non-coding DNA by finding the sequence is "conserved" or "constrained" (i.e. similar) across diverse species, implying there is some kind of selectable function preventing it from accumulating mutations. But if a sequence is not conserved or constrained (i.e. it's different) across different species, does that imply it's not functional? The ENCODE asked this question, and found the answer is "no":

Primate-specific elements as well as elements without detectable mammalian constraint show, in aggregate, evidence of negative selection; thus, some of them are expected to be functional

Later the paper found that within primates, unconserved sequences may be very important for determining body form:

There are also a large number of elements without mammalian constraint, between 17% and 90% for transcription-factor binding regions as well as DHSs and FAIRE regions. Previous studies could not determine whether these sequences are either biochemically active, but with little overall impact on the organism, or under lineage specific selection. By isolating sequences preferentially inserted into the primate lineage, which is only feasible given the genome-wide scale of this data, we are able to examine this issue specifically. ... [A]n appreciable proportion of the unconstrained elements are lineage-specific elements required for organismal function, consistent with long-standing views of recent evolution, and the remainder are probably "neutral" elements that are not currently under selection but may still affect cellular or larger scale phenotypes without an effect on fitness. (internal citations omitted)

And of course, if a genetic element affects "cellular or larger scale phenotypes," then clearly those elements have function as well.

Findings are "Unprecedented"

The paper concludes that researchers have uncovered an "unprecedented number of functional elements":

The unprecedented number of functional elements identified in this study provides a valuable resource to the scientific community as well as significantly enhances our understanding of the human genome.

They also make the obvious conclusion that much more of the genome appears to be involved in regulation processes than producing biochemically active proteins:

Interestingly, even using the most conservative estimates, the fraction of bases likely to be involved in direct gene regulation, even though incomplete, is significantly higher than that ascribed to protein coding exons (1.2%), raising the possibility that more information in the human genome may be important for gene regulation than for biochemical function.

And of course, the implications of this study for fighting disease are profound:

The broad coverage of ENCODE annotations enhances our understanding of common diseases with a genetic component, rare genetic diseases, and cancer, as shown by our ability to link otherwise anonymous associations to a functional element.
Junk DNA Will Be "Consigned to the History Books"

The news media have picked up on this story, with headlines like

"Breakthrough study overturns theory of 'junk DNA' in genome" (UK Guardian) or "Bits of Mystery DNA, Far From 'Junk,' Play Crucial Role" (NY Times).

These articles frankly acknowledge the implications for the old "junk DNA" notion:

• "Long stretches of DNA previously dismissed as "junk" are in fact crucial to the way our genome works, an international team of scientists said on Wednesday. ... For years, the vast stretches of DNA between our 20,000 or so protein-coding genes -- more than 98% of the genetic sequence inside each of our cells -- was written off as "junk" DNA. Already falling out of favor in recent years, this concept will now, with Encode's work, be consigned to the history books." (Alok Jha, "Breakthrough study overturns theory of 'junk DNA' in genome," UK Guardian (September 5, 2012))
• "The human genome is packed with at least four million gene switches that reside in bits of DNA that once were dismissed as 'junk' but that turn out to play critical roles in controlling how cells, organs and other tissues behave. The discovery, considered a major medical and scientific breakthrough, has enormous implications for human health because many complex diseases appear to be caused by tiny changes in hundreds of gene switches. ... Human DNA is 'a lot more active than we expected, and there are a lot more things happening than we expected,' said Ewan Birney of the European Molecular Biology Laboratory-European Bioinformatics Institute, a lead researcher on the project." (Gina Kolata, "Bits of Mystery DNA, Far From 'Junk,' Play Crucial Role," New York Times (September 5, 2012))

The NY Times further commented on the complexity of what we're finding:

There also is a sort of DNA wiring system that is almost inconceivably intricate.
"It is like opening a wiring closet and seeing a hairball of wires," said Mark Gerstein, an Encode researcher from Yale. "We tried to unravel this hairball and make it interpretable."

There is another sort of hairball as well: the complex three-dimensional structure of DNA. Human DNA is such a long strand -- about 10 feet of DNA stuffed into a microscopic nucleus of a cell -- that it fits only because it is tightly wound and coiled around itself. When they looked at the three-dimensional structure -- the hairball -- Encode researchers discovered that small segments of dark-matter DNA are often quite close to genes they control. In the past, when they analyzed only the uncoiled length of DNA, those controlling regions appeared to be far from the genes they affect.
Over at Discover Magazine, Tom Gingeras, a senior scientist affiliated with ENCODE, states that "Almost every nucleotide is associated with a function":

According to ENCODE's analysis, 80 percent of the genome has a "biochemical function". More on exactly what this means later, but the key point is: It's not "junk". Scientists have long recognised that some non-coding DNA probably has a function, and many solid examples have recently come to light. But, many maintained that much of these sequences were, indeed, junk. ENCODE says otherwise. "Almost every nucleotide is associated with a function of some sort or another, and we now know where they are, what binds to them, what their associations are, and more," says Tom Gingeras, one of the study's many senior scientists.

The Discover Magazine article further explains that the rest of the 20% of the genome is likely to have function as well:
And what's in the remaining 20 percent? Possibly not junk either, according to Ewan Birney, the project's Lead Analysis Coordinator and self-described "cat-herder-in-chief". He explains that ENCODE only (!) looked at 147 types of cells, and the human body has a few thousand. A given part of the genome might control a gene in one cell type, but not others. If every cell is included, functions may emerge for the phantom proportion. "It's likely that 80 percent will go to 100 percent," says Birney. "We don't really have any large chunks of redundant DNA. This metaphor of junk isn't that useful."
We will have more to say about this blockbuster paper from ENCODE researchers in coming days, but for now, let's simply observe that it provides a stunning vindication of the prediction of intelligent design that the genome will turn out to have mass functionality for so-called "junk" DNA. ENCODE researchers use words like "surprising" or "unprecedented." They talk about of how "human DNA is a lot more active than we expected." But under an intelligent design paradigm, none of this is surprising. In fact, it is exactly what ID predicted.

This important paper also represents a stunning vindication of Jonathan Wells's book The Myth of Junk DNA. He wrote there:

Far from consisting mainly of junk that provides evidence against intelligent design, our genome is increasingly revealing itself to be a multidimensional, integrated system in which non-protein-coding DNA performs a wide variety of functions. If anything, it provides evidence for intelligent design. Even apart from possible implications for intelligent design, however, the demise of the myth of junk DNA promises to stimulate more research into the mysteries of the genome. These are exciting times for scientists willing to follow the evidence wherever it leads.

(Jonathan Wells, The Myth of Junk DNA, pp. 9-10 (Discovery Institute Press, 2011).)
While undoubtedly a few holdouts will continue to defend "junk DNA" thinking for philosophical or theological reasons, this paper should put most arguments in favor of junk DNA to rest.

Image credit: rusty one/Flickr

那個＂80%junk說＂本來就有點匪宜所思，但不知道"junk no more" 怎麼就支持"intelligent design說"了＂？

我看"intelligent design說"還是不要跟gene過不去了，還是先解釋一個簡單點的問題吧：design男人的奶頭有什麼用？

研究竟然不反對科學了, 不怕研究結果和進化論吻合,不怕講究結果和聖經衝突了?

hellman 發表於 2012-9-7 00:28
研究竟然不反對科學了, 不怕研究結果和進化論吻合,不怕講究結果和聖經衝突了?  ...

我什麼時候反科學了？我本身就是科學工作者。

BenAl 發表於 2012-9-6 23:09
那個＂80%junk說＂本來就有點匪宜所思，但不知道"junk no more" 怎麼就支持"intelligent design說"了＂？

...

說是為了美，為了性感。你信嗎？上帝願意怎麼design就怎麼design。

好好讀文章。

研究 發表於 2012-9-7 01:13
說是為了美，為了性感。你信嗎？上帝願意怎麼design就怎麼design。

好好讀文章。 ...

你這個好象是為"80%junk"而辯護的: ＂上帝願意怎麼design就怎麼design＂，那design大部分無用又如何？

哈哈，為＂性感＂？你自己信嗎？你念１０００遍＂十戒＂去吧。

研究 發表於 2012-9-7 01:11
我什麼時候反科學了？我本身就是科學工作者。

要吃飯當然要工作了. 我前天就看了這個新聞. 還查了項目啟動時遇到的困難主要是宗教組織的反對. 像你這樣的科學家肯定矛盾的很.

沒看明白。

BenAl 發表於 2012-9-7 01:39
你這個好象是為"80%junk"而辯護的: ＂上帝願意怎麼design就怎麼design＂，那design大部分無用又如何？

...

你看明白了?

來往加國 發表於 2012-9-7 09:33
沒看明白。

這是對今天自然雜誌發表的巨作的點評.

hellman 發表於 2012-9-7 06:43
要吃飯當然要工作了. 我前天就看了這個新聞. 還查了項目啟動時遇到的困難主要是宗教組織的反對. 像 ...

不明白為什麼宗教組織要反對?

BenAl 發表於 2012-9-7 01:39
你這個好象是為"80%junk"而辯護的: ＂上帝願意怎麼design就怎麼design＂，那design大部分無用又如何？

...

你沒看明白. 好好看看再說話, 省得讓人笑話. 最好看看自然的原文, 希望你能看懂.

Strikingly, the data overturn old ideas that the bulk of DNA in our cells is useless — albeit inoffensive — junk just carried along for the evolutionary ride. Back in 2003 when the human genome was published, scientists estimated that less than 2% of it carries instructions for making proteins, and many of them thought the rest didn』t do very much.

But the new analysis shows that more than 80% of the human genome is active in at least one biological process that the ENCODE team measured. Nearly every part of it could end up being active when the data are more complete.

The discoveries were published on Wednesday in six papers in the journal Nature and in 24 papers in Genome Research and Genome Biology. In addition, The Journal of Biological Chemistry is publishing six review articles, and Science is publishing yet another article.

[...]The thought before the start of the project, said Thomas Gingeras, an Encode researcher from Cold Spring Harbor Laboratory, 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. Before Encode, said Dr. John Stamatoyannopoulos, a University of Washington scientist who was part of the project, 「if you had said half of the genome and probably more has instructions for turning genes on and off, I don』t think people would have believed you.」

It』s just another prediction of Darwinian orthodoxy falsified by experimental evidence published in the top scientific peer-reviewed journal. Will this cause Darwinians to revise their theory to fit the evidence? Not likely. Their motivations for clinging to naturalism, the religion that undergirds Darwinism, are entirely beyond correction by evidence.

研究 發表於 2012-9-7 12:00
你沒看明白. 好好看看再說話, 省得讓人笑話. 最好看看自然的原文, 希望你能看懂. ...

這有什麼難的嗎？難道不是說原來認為只有很少有用，現在卻發現大部分都有用了？

研究 發表於 2012-9-7 12:34
It』s just another prediction of Darwinian orthodoxy falsified by experimental evidence published in ...

這個評論是誰做的？很有JDT的特徵，在原作者還沒說什麼之前，就搶先替別人解釋了。

研究 發表於 2012-9-7 11:57
不明白為什麼宗教組織要反對?

Human Genome Shows Proof of Recent Evolution, Survey Finds

http://news.nationalgeographic.c ... 0308_evolution.html

Scott Norris
for National Geographic News

March 8, 2006
Signs of recent evolution by natural selection are widespread across the human genome, experts say.

Genome researchers at the University of Chicago have identified more than 700 regions in human DNA where apparently strong selection has occurred, driving the spread of genes linked to a broad range of characteristics.

The results suggest that humans in different regions have continued to adapt in numerous ways to both environmental changes and cultural innovations.

Many of the genetic changes Pritchard's group detected came during or after the emergence of agriculture, beginning about 10,000 years ago, and long after the formation of modern human populations.

Some of the genes most strongly affected by selection were those associated with skin color, bone structure, and the metabolism of different foods.

Using newly available data, the scientists conducted a genome-wide scan for genetic variants showing evidence of recent selection in European, Asian, and African populations.

Most of the selected genes varied strongly among the three groups, suggesting that humans were adapting to pressures specific to different parts of the world.

The results are published in this month's issue of the journal PLoS Biology.

Changing World, Changing Genes

Positive selection occurs when a specific gene gives its carriers some advantage over others who lack the gene.

The findings, along with other recent studies, begin to provide a kind of genetic narrative of recent human evolution.

Joshua Akey, a genetics researcher at the University of Washington in Seattle, says selection-driven changes recorded in the genome provide tantalizing clues about past challenges faced by humans.



"These are all potentially strong selective forces, which Dr. Pritchard and his colleagues appear to have captured in their analysis."

For example, major changes in diet occurred as nomadic hunter-gatherers slowly shifted to a settled agricultural existence.

Pritchard says this transition left a legacy of strong selection on genes associated with the processing of carbohydrates and fatty acids.

The clearest example—one previously known about by researchers—is the gene that allows for the digestion of milk into adulthood.

Among Europeans, whose ancestors relied on milk products as an important food source, this gene has become widespread. In most other human populations the gene is rare.

The study also provides new evidence that mutations to better digest different food products have spread in other groups.

Asian and African populations showed selection in genes affecting the metabolism of the plant sugars mannose and sucrose.

All three groups also showed selection for different genes involved in the uptake, storage, and energy conversion of dietary fats.

Another previously unreported example of natural selection involves the genes that people today rely on to process most pharmaceutical products.

Changes in these genes may be a legacy of human exposure to toxic plant compounds, either through a diet of wild foods or deliberate medicinal uses.

Physical Differences

Genes related to physical characteristics also showed strong evidence of selection, with interesting differences among the three populations.

"We found five different genes involved in skin pigmentation in the European population," Pritchard said.

He noted that, for humans living far from the equator, lighter skin is important for producing vitamin D, which is often formed in the body following exposure to the sun's ultraviolet rays.

Pritchard says evidence of recent pigmentation changes in Europeans may be the tail end of a much older process underway since modern humans first moved out of Africa or Asia to higher latitudes.

But the genetic changes could also be a reflection of more recent northward migrations following the last Ice Age, about 14,000 years ago, he says.

The survey also turned up evidence of selection in genes affecting skeletal development in Europeans and Asians and hair formation in Africans.

Pritchard says that while proteins involved in these processes were clearly targeted, it is still too early to say exactly why the changes occurred or what the evolutionary outcomes may have been.

Disease Selection

Evidence of different selective pressures operating on different populations may be medically important, says study lead author Benjamin Voight.

Discovering genes that contribute to common human diseases is always difficult, Voight said.

But "our hope is that the identification of selective targets using evolutionary theory might give other researchers a starting point."

Many disease-related genes should leave a strong signal of selection, because they influence individual survival.

By examining how selection has operated on different populations, researchers may be able to track down the genes underlying conditions such as diabetes, hypertension, and obesity, which vary in incidence and severity across ethnic groups.

"This research may provide the foundation for understanding how human evolutionary history has contributed to the susceptibility to complex diseases," the University of Washington's Akey said.

"Genome-wide scans for selection are not an end but rather an exciting beginning."



The methods used by Pritchard's group detected apparently beneficial genes that have spread through a large portion of the population but are not yet universal.

http://darwins-god./2010/03/sean-carroll-on-why-dna-proves.html


Sean Carroll on Why DNA Proves Evolution

In his book The Making of the Fittest, Sean Carroll writes 「the degree of similarity in DNA is an index of the [evolutionary] relatedness of species.」 [98] This can only make sense if we first assume evolution is true. But Carroll's book is a defense of evolution, intended to demonstrate that the theory is true without first assuming it is true. He seeks to prove evolution is true, but he begins with evolutionary reasoning and interpretations. That is circular reasoning. Unfortunately such circular reasoning is a common motif in the evolution genre.

In recent years the genomes of various species have been decoded. It is an avalanche of disparate data, as genomes can contain a variety of types of messages. For evolutionists, these messages hold many secrets of evolutionary history. If the species share common ancestors, then the contents of their genomes should help decipher that evolutionary history.

For instance, mobile genetic elements are genome segments that can move about, inserting themselves at various locations within the genome. These insertions, according to evolutionists, are a random affair. After all, evolutionists assume that life is a fluke, and biology is one big kludge.

A few years back evolutionists claimed that retroviruses found in primate genomes proved common descent. The retroviruses, it was said, were the perfect evolutionary sign post. They were assumed to insert randomly into the genome and once inserted to stay put. Therefore, if two cousin species shared a similar pattern of retroviruses, then those retroviruses must have been inherited from a common ancestor. It would be too great of a coincidence for the retroviruses to have independently inserted into the two genomes (notice the circular reasoning).

These assumptions are routinely revised. Retroviruses patterns were found that cannot be explained by common descent (e.g., same pattern in only two of three cousin species). Apparently the retroviruses were not such perfect evolutionary sign posts as had been assumed. But evolutionists viewed such cases as anomalies, and rationalized them using ad hoc explanations. Such falsifiers have long since been discovered. They are just not advertised.

This dynamic has repeated itself with other types of genetic messages, such as pseudogenes and interspersed elements. Here is what Carroll had to say about the latter:


These landmarks are produced by accidental insertions of junk DNA sequences near genes. ... Once [an interspersed element] is inserted, there is no active mechanism for removing it. The insertion of these elements marks a gene in a species, and is then inherited by all species descended from it. They are really perfect tracers of genealogy. [99]

Except, that is, when they aren't. This is simply a misrepresentation. Like retroviruses, and pseudogenes, interspersed elements occasionally violate the evolutionary pattern. Apparently they are not quite such 「perfect tracers of genealogy.」 To be sure, such outliers are unusual, but if they can be explained by mechanism (rather than inheritance), then so can the others. Carroll concludes that the interspersed elements:


can be explained only by the species sharing a common ancestor. ... biologists have sufficient forensic evidence to determine species' kinship beyond any doubt. [99]

This is, of course, false. In fact, interspersed elements patterns are explained without resorting to a common ancestor and the tremendous problems with such an explanation.
Posted by Cornelius Hunter at Wednesday, March 03, 2010

hellman 發表於 2012-9-8 02:00
http://darwins-god./2010/03/sean-carroll-on-why-dna-proves.html

這隻不過是達爾文主義的最後的嚎叫罷了. 物種間基因相近, 不等於是進化的, 波音747 也不是波音737進化來的. 它們都是由設計者設計的.