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Genetics Leaves Central Dogma and Junk DNA in the Rear-View Mirror

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Today, we look at some discoveries that continue to leave the Central Dogma and “junk DNA” in the rear-view mirror. Through the front windshield, we see discoveries about epigenetics coming fast.

New Form of Regulatory DNA

A “mysterious” form of DNA shaped like a four-stranded knot, once thought to exist only in the lab, has been discovered to be active in cell nuclei. Yasemin Saplakoglu reports in Live Science that “many scientists thought that it couldn’t possibly exist in human cells,” because it loves acidic environment not found naturally in the body. Called an i-motif, the structure has been now reported by Australian scientists in a paper in Nature Chemistry, and the rush is on to see what it does. Saplakoglu thinks “it may play an important role in regulating our genes.” Co-author Marcel Dinger sees much more to discover in the forward view:

“There’s so much of the genome that we don’t understand, probably like 99 percent of it,” Dinger said. Seeing DNA folded like this in living cells “makes it possible to decode those parts of the genome and understand what they do.” [Emphasis added.]

Bye-Bye Junk; Hello Captain

How often have we heard about new roles for junk DNA? Here’s another: “A conserved function for pericentromeric satellite DNA” announced in the journal eLife by researchers at the University of Michigan. This one got promoted from junk to captain:

A universal and unquestioned characteristic of eukaryotic cells is that the genome is divided into multiple chromosomes and encapsulated in a single nucleus. However, the underlying mechanism to ensure such a configuration is unknown. Here we provide evidence that pericentromeric satellite DNA, which is often regarded as junk, is a critical constituent of the chromosome, allowing the packaging of all chromosomes into a single nucleus.

Old-school geneticists considered this kind of DNA as “junk” or “selfish” DNA that perpetuated itself for no purpose, says Science Daily. But lead author Yukiko Yamashita and colleagues “were not quite convinced by the idea that this is just genomic junk.” For one thing, it is highly conserved, so “If we don’t actively need it, and if not having it would give us an advantage, then evolution probably would have gotten rid of it. But that hasn’t happened.” When they took a closer look, they found that cells in fruit flies, mice, humans and probably all vertebrates cannot survive without it. Using a protein named D1 that binds to the satellite DNA, they found it provides vital attachment points for molecular machines that keep chromosomes in the nucleus. Without it, DNA would float off into buds with only part of the genome, and the cell would die.

The similar findings from both fruit fly and mouse cells lead Yamashita and her colleagues to believe that satellite DNA is essential for cellular survival, not just in model organisms, but across species that embed DNA into the nucleus — including humans.

Genetics Without the “Epi” Prefix Is Incomplete

A geneticist at Johns Hopkins is telling colleagues not to forget the “epi” in genetics research. “In a review article published April 5 in the New England Journal of Medicine, scientist Andrew Feinberg, M.D., calls for more integration between two fields of DNA-based research: genetics and epigenetics.” It is essential for human disease prevention and mitigation, Feinberg notes, but from his vantage point, “scientists know comparatively little about how existing drugs may be altering patients’ epigenomes.” 

He suggests that combining genomewide and epigenomewide association studies can overcome problems of assigning cause and effect to specific alterations among either type of study alone.

Identity Crisis Solved

Why do cells with identical genes perform unique jobs? Consider how different a blood cell is from a brain cell, and yet they both share the same genome in their nuclei. Researchers at Trinity College Dublin explored the question of “cellular identity,” which they say is “central to the field of epigenetics,” and “made a significant discovery that explains how and why the billions of different cells in our bodies look and act so differently despite containing identical genes.”

Central to this is a group of epigenetic regulators, called Polycombs, which are vital to regulating cellular identity in multicellular organisms of both the plant and animal kingdoms. The Bracken lab studies the biology of these Polycomb epigenetic regulators, and their newly discovered PALI1 and PALI2 proteins form a new family of Polycombs that are unique in that they are only present in vertebrates — they are not found in invertebrate animals, or plants.

The uniqueness of these regulators to vertebrate animals does not mean that plants and invertebrates lack mechanisms to achieve cellular identity; they just have different ones.

The Anti-Dogmatists

Confidence in the Central Dogma been collapsing for a long time now. The idea that DNA is the master molecule, making RNA that makes proteins and that’s all you need to know — taught uncritically since the 1960s — cannot stand up to all the new discoveries. At The Conversation, Staffan Müller-Wille and Hans-Jörg Rheinberger explain “Why genes don’t hold all the answers for biologists.”

It is still widely believed that the gene is the foundation of life — that its discovery has provided information about how all living beings are controlled by the genetic factors they inherit from their parents.

But scientists and philosophers are beginning to doubt the relevance of the gene for understanding biology.

Despite being central to the subject for over a century, there has never been a universally accepted, constant definition of what genes actually are. From the beginning, scientists have tried to link human characteristics to genes, but had limited success in establishing stable connections.

Rheinberger is a historian of science at the Max Planck Institute. Together, the two produced a book called The Gene: From Genetics to Postgenomics that undermines the neat picture of genetics as a triumph of 20th-century science. While readers of the press release will enjoy the short video biography of Gregor Mendel, the 19th-century father of genetics whose work was largely ignored until well into the 20th century, genetics today is much more complicated. 

Biologists will of course continue to talk about genes in the future. But genes will no longer be seen as the blueprint for life, even if technological and medical applications of gene technology suggest this. Instead, they are increasingly seen as only one of the many resources that organisms make use of in adapting to challenges in their environments.

Conclusion

The old genetics of the late 20th century was powerful enough evidence of intelligent design, with its systems of highly-accurate transcription and translation of encoded information. Now, we find that the old picture was far too simplistic. And the surprising lack of “genes” found by the Human Genome Project, feeding rumors of useless “junk” pervading our genome, is rapidly being supplanted by evidence of hierarchical codes and functions everywhere. 

If the old genetics was sufficient to allow A.E. Wilder-Smith to help convince Matti Leisola to become a Darwin Heretic in the 1970s (pp. 40-41), how much more will the flood of new discoveries, illustrated by these few examples, persuade the next generation of geneticists that Darwinism is hopelessly inadequate to account for the complexity of life? It’s like having to account for half a dozen codes instead of one. The future looks bright for ID in next-generation genetics, embedded in epigenetics. The nucleus is a whole new ball game.

Photo credit: Jack, via Flickr.