September 3, 2014

More Light Is Cast on Epigenetics and Design

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by Evolution News & Views

The study of epigenetics — codes and systems “above” genetics — has accelerated in recent years. Scientists now recognize a multitude of players implicated in regulating genes. These players include proteins, RNA molecules, and chemical “tags” that DNA translation machinery recognizes. Some recent papers elucidate a few of the many ways epigenetic factors interact with the genome.

Epigenetics in Embryology

When an embryo develops, epigenetic factors really go into action, because decisions must be made continually about what genes need to be activated as cells rapidly multiply and differentiate. The Ludwig Institute for Cancer Research described three classes of genes that respond to different epigenetic controls. Some DNA bases (particularly cytosine) are tagged with methyl groups that silence the gene. Some genes are left untagged, as if to leave them open for expression. That the system is vital is underscored by what can go wrong:

The researchers also found that the human genome is peppered with more than 1,200 large regions that are consistently devoid of DNA methylation throughout development. It turns out that many of the genes considered master regulators of development are located in these regions, which the researchers call DNA methylation valleys (DMVs). Further, the team found that the DMVs are abnormally methylated in colon cancer cells. While it has long been known that aberrant DNA methylation plays an important role in various cancers, these results suggest that changes to the cell’s DNA methylation machinery itself may be a major step in the evolution of tumors. (Emphasis added.)

A third class of genes are not tagged directly on the DNA bases, but are silenced via tags on the histone proteins that DNA is wrapped around. This is all very logical, the press release said:

“You can sort of glean the logic of animal development in this difference,” says Ren. “Histone methylation is relatively easy to reverse. But reversing DNA methylation is a complex process, one that requires more resources and is much more likely to result in potentially deleterious mutations. So it makes sense that histone methylation is largely used to silence master genes that may be needed at multiple points during development, while DNA methylation is mostly used to switch off genes at later stages, when cells have already been tailored to specific functions, and those genes are less likely to be needed again.”

In their four-year research into epigenomics, the team also cataloged enhancers that promote gene expression. Once again, this was all very logical, according to Bing Ren, Ludwig Institute Member and professor at UC San Diego School of Medicine:

Further, the researchers catalogued the regulation of DNA sequences known as enhancers, which, when activated, boost the expression of genes. They identified more than 103,000 possible enhancers and charted their activation and silencing in six cell types. Researchers will in all likelihood continue to sift through the data generated by this study for years to come, putting the epigenetic phenomena into biological context to investigate a variety of cellular functions and diseases.

These data are going to be very useful to the scientific community in understanding the logic of early human development,” says Ren.

Epigenetics in Nuclear Organization

RNA molecules can also have epigenetic effects. Science Magazine described how long noncoding RNAs (lncRNA) may have a surprising function: organizing the 3-D structure of DNA in the nucleus. Elizabeth Pennisi set the stage for a contest between “junk” and “function” for these enigmatic RNA molecules:

Our 21,000 protein-coding genes aren’t the only readable units in our genome. At last count, another 13,000 “genes” specify mysterious molecules called long noncoding RNAs (lncRNAs), and when the final tallies are in, they may outnumber protein-coding genes. But what are these RNAs good for? Some researchers have suggested that they represent “noise”: DNA randomly converted to RNA that serves no purpose. Others propose that they may be as pivotal as proteins in guiding cellular processes.

The remainder of the article discussed a specific case: a lncRNA named XIST, that “operates by interacting with loops of nearby chromosome.” Notice how design thinking turned on the lights for one researcher:

“It seems to be creating a three-dimensional organization, bringing together regions of the genome in a way that we had assumed proteins were doing,” says Emmanouil Dermitzakis, a genomicist from the University of Geneva in Switzerland. This finding supports a role for lncRNAs in regulating chromosomal activity by influencing the shape of chromatin, the protein complex that swaddles DNA. “It gives us a model of how other lncRNAs might be active,” Dermitzakis adds.

Though much remains to be learned about lncRNAs, this example shows that a function can be found by reasoning logically that it must be there for a purpose. Another genomicist remarked, “It’s possible that lncRNAs represent a new type of gene regulator.”

Epigenetics in Structure

Another mystery of the human genome was why there are long, repetitive sequences. One example of a function for some of them was discovered by the Friedrich Miescher Institute for Biomedical Research: “They show in the renowned scientific journal Cell, how three proteins interact on the repetitive sequences at the chromosomal ends, the telomeres, to form a powerful protein scaffold required for telomere homeostasis.” Cells are glad to have these seemingly useless repetitive sequences. Why? They don’t want to die:

The genome is full of sequence repetitions. Sequence motive [sic, motif] is added after sequence motive, sometimes more than a hundred times. Erratically it seems. And these sequence motives bind proteins that control transcription factors in regions of the genome where no transcription should occur. A conundrum. Nicolas Thomä, group leader at the Friedrich Miescher Institute for Biomedical Research, and his team together with the team of David Shore at the University of Geneva, have now been able to give an answer and assign a function to this seeming inconsistency. In a study published today in Cell, they elucidated how sequence repeats in telomeres help stabilize these regions and prevent cell death.

Thomä added a prediction for other repetitive sequences: “This is a novel concept and could explain how other regions of the genome with sequence repetitions function to control transcription and cell fate.”

Epigenetics and Environment

For these and other reasons, Denise Chow at Live Science says that “DNA May Not Be Your Destiny.” She recalls how scientists expected to understand every human disease and behavior by mapping the genome. When the Human Genome Project was completed, something was missing — and it was epigenetics. As the ENCODE project showed, vast quantities of seemingly useless “junk DNA” are expressed, not for making proteins, but for switching genes on and off. The new science of epigenetics, Chow explains, is providing a new level of understanding of how genes are regulated — and how the environment can affect gene expression in heritable ways.

Epigenetics and Evolution

In another article at Live Science, Tia Ghose suggests that epigenetics makes the current theory of evolution inadequate: “some researchers think the modern consensus on evolutionary theory may need to be extended to encompass epigenetics.” But since epigenetics is “incredibly complicated,” evolutionary theory will need an overhaul, not just a patch. Laurel Fogarty from Stanford commented on several of the new discoveries:

“Findings like these show clearly that we need to broaden our understanding of how natural selection, genes and non-genetic inheritance interact if we want to fully understand evolution,” Fogarty wrote.

The statement implies that evolution is not fully understood, nor can it be unless this “incredibly complicated” epigenetic information, which may dwarf the information content of DNA, is understood. What, then, of 154 years of bluffing that evolution is well-understood science?

Epigenetics and Intelligent Design

In Signature in the Cell, Stephen Meyer inferred that intelligent design stands as the best explanation for the information content of DNA. That was in 2009, before the ENCODE revelations. Now, ongoing discoveries of even higher levels of epigenetic information are amplifying that inference. While evolutionists scramble to deal with the unprecedented complexity, intelligent design is not surprised by it. Design thinking propelled the discovery of functions for what evolutionists considered useless leftovers of a haphazard process, as the above reports show.

The lesson is clear: intelligent design is in the best position to promote scientific discovery, and to deliver the understanding sought by science.

Read the Full Article Here: http://www.evolutionnews.org/2013/06/more_light_is_c073041.html

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