Discovery of Intron Function Interrupts Evolutionary Paradigm

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BY FAZALE RANA – MARCH 6, 2019

Nobody likes to be interrupted when they are talking. It feels disrespectful and can be frustrating. Interruptions derail the flow of a conversation.

The editors tell me that I need to interrupt this lead to provide a “tease” for what is to come. So, here goes: Interruptions happen in biochemical systems, too. Life scientists long thought that these interruptions disrupted the flow of biochemical information. But, it turns out these interruptions serve an important function, offering a rejoinder a common argument against intelligent design.

Now back to the lead.

Perhaps it is no surprise that some psychologists study interruptions1 with the hope of discovering answers to questions such as:

  • Why do people interrupt?
  • Who is most likely to interrupt?
  • Do we all perceive interruptions in the same way?

While there is still much to learn about the science of interruptions, psychologists have discovered that men interrupt more often than women. Ironically, men often view women who interrupt as ruder and less intelligent than men who interrupt during conversations.

Researchers have also found that a person’s cultural background influences the likelihood that he or she will interrupt during a discourse. Personality also plays a role. Some people are more sensitive to pauses in conversation and, therefore, find themselves interrupting more often than those who are less uncomfortable with periods of silence.

Psychologists have learned that not all interruptions are the same. Some people interrupt because they want the “floor.” These people are called intrusive interrupters. Cooperativeinterrupters help move the conversation along by agreeing with the speaker and finishing the speaker’s thoughts.

Interruptions are not confined to conversations. They are a part of life, including the biochemical operations that take place inside the cell.

In fact, biochemists have discovered that the information harbored in genes, which contains the instructions to build proteins—the workhorse molecules of the cell—experience interruptions in their coding sequences. These intrusive interruptions would disrupt the flow of information in the cell during the process of protein synthesis if the interrupting sequences weren’t removed by the cell’s machinery.

Molecular biologists have long viewed these genetic “interruptions” (called introns) as serving no useful purpose for the cell, with introns comprising a portion of the junk DNA found in the genomes of eukaryotic organisms. But it turns out that introns—like cooperative interruptions during a conversation—serve a useful purpose, according to the recent work of two independent teams of molecular biologists.

Introns Are Abundant

Noncoding regions within genes, introns consist of DNA sequences that interrupt the coding regions (called exons) of a gene. Introns are pervasive in genomes of eukaryotic organisms. For example, 90 percent of genes in mammals consists of introns, with an average of 8 per gene.

After the information stored in a gene is copied into messenger RNA, the intron sequences are excised, and the exons spliced together by a protein-RNA complex known as a spliceosome.

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Figure 1: Drawing of pre-mRNA to mRNA. Image credit: Wikipedia

Molecular biologists have long wondered why eukaryotic genes would be riddled with introns. Introns seemingly make the structure and expression of eukaryotic genes unnecessarily complicated. What possible purpose could introns serve? Researchers also thought that once the introns were spliced out of the messenger RNA sequences, they were discarded as genetic debris.

Introns Serve a Functional Purpose

But recent work by two independent research teams from Sherbrooke University in Quebec, Canada, and MIT, respectively, indicates that molecular biologists have been wrong about introns. They have learned that once spliced from messenger RNA, these fragments play a role in helping cells respond to stress.

Both research teams studied baker’s yeast. One advantage of using yeast as a model organism relates to the relatively small number of introns (295) in its genome.

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Figure 2: A depiction of baker’s yeast. Image credit: Shutterstock

Taking advantage of the limited number of introns in baker’s yeast, the team from Sherbrooke University created hundreds of yeast strains—each one missing just one of its introns. When grown under normal conditions with a ready supply of available nutrients, the strains missing a single intron grew normally—suggesting that introns aren’t of much importance. But when the researchers grew the yeast cells under conditions of food scarcity, the yeast with the deleted introns frequently died.2

The MIT team observed something similar. They noticed that during the stationary phase of growth (when nutrients become depleted, slowing down growth), introns spliced from RNA accumulated in the growth medium. The researchers deleted the specific introns that they found in the growth medium from the baker’s yeast genome and discovered that the resulting yeast strains struggled to survive under nutrient-poor conditions.3

At this point, it isn’t clear how introns help cells respond to stress caused by a lack of nutrients, but they have some clues. The Sherbrooke University team thinks that the spliced-out introns play a role in repressing the production of proteins that help form ribosomes. These biochemical machines manufacture proteins. Because protein synthesis requires building block materials and energy, during periods when nutrients are scarce, protein production slows down in cells. Ratcheting down protein synthesis impedes cell growth but affords them a better chance to survive a lack of nutrients. One way cells can achieve this objective is to stop making ribosomes.

The MIT team thinks that some spliced-out introns interact with spliceosomes, preventing them from splicing out other introns. When this disruption happens, it slows down protein synthesis.

Both research groups believe that in times when nutrients are abundant, the spliced-out introns are broken down by the cell’s machinery. But when nutrients are scarce, that condition triggers intron accumulation.

At this juncture, it isn’t clear if the two research teams have uncovered distinct mechanisms that work collaboratively to slow down protein production, or if they are observing facets of the same mechanism. Regardless, it is evident that introns display functional utility. It’s a surprising insight that has important ramifications for our understanding of the structure and function of genomes. This insight has potential biomedical utility and theological implications, as well.

Intron Function and the Case for Creation

Scientists who view biology through the lens of the evolutionary paradigm are quick to conclude that the genomes of organisms reflect the outworking of evolutionary history. Their perspective causes them to see the features of genomes, such as introns, as little more than the remnants of an unguided evolutionary process. Within this framework, there is no reason to think that any particular DNA sequence element, including introns, harbors function. In fact, many life scientists regard the “evolutionary vestiges” in the genome as junk DNA. This clearly has been the case for introns.

Yet, a growing body of data indicates that virtually every category of so-called junk DNA displays function. We can now add introns—cooperative interrupters—to the list. And based on the data on hand, we can make a strong case that most of the sequence elements in genomes possess functional utility.

Could it be that scientists really don’t understand the biology of genomes? Or maybe we have the wrong paradigm?

It seems to me that science is in the midst of a revolution in our understanding of genome structure and function. Instead of being a wasteland of evolutionary debris, most of the genome appears to be functional. And the architecture and operations of genomes appear to be far more elegant and sophisticated than anyone ever imagined—at least within the confines of the evolutionary paradigm.

But what if the genome is viewed from a creation model framework?

The elegance and sophistication of genomes are features that are increasingly coming into scientific view. And this is precisely what I would expect if genomes were the product of a Mind—the handiwork of a Creator.

Now that is a discovery worth talking about.

Resources

Endnotes
  1. Teal Burrell, “The Science behind Interrupting: Gender, Nationality and Power, and the Roles They Play,” Post Magazine (March 14, 2018), https://www.scmp.com/magazines/post-magazine/long-reads/article/2137023/science-behind-interrupting-gender-nationality; Alex Shashkevich, “Why Do People Interrupt? It Depends on Whom You’re Talking To,” The Guardian (May 18, 2018), https://www.theguardian.com/lifeandstyle/2018/may/18/why-do-people-interrupt-it-depends-on-whom-youre-talking-to.
  2. Julie Parenteau et al., “Introns Are Mediators of Cell Response to Starvation,” Nature 565 (January 16, 2019): 612–17, doi:10.1038/s41586-018-0859-7.
  3. Jeffrey T. Morgan, Gerald R. Fink, and David P. Bartel, “Excised Linear Introns Regulate Growth in Yeast,” Nature 565 (January 16, 2019): 606–11, doi:10.1038/s41586-018-0828-1.

Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2019/03/06/discovery-of-intron-function-interrupts-evolutionary-paradigm

Ribosomes: Manufactured by Design, Part 2

ribosomesmanufacturedbydesign

BY FAZALE RANA – NOVEMBER 8, 2017

“I hope there are no creationists in the audience, but it would be a miracle if a strand of RNA ever appeared on the primitive Earth.”1

Hugh Ross and I witnessed the late origin-of-life researcher, Leslie Orgel, make this shocking proclamation at the end of a lecture he presented at the 13th International Conference on the Origin of Life (ISSOL 2002).

Orgel was one of the originators of the RNA world hypothesis. And because of his prominence in the origin-of-life research community, the conference organizers granted Orgel the honor of opening ISSOL 2002 with a plenary lecture on the status of the RNA world hypothesis. During his presentation, Orgel described problem after problem with the leading origin-of-life explanation, reaching the tongue-in-cheek conclusion that it would require a miracle for this evolutionary scenario to yield RNA, let alone the first life-forms. (For a detailed discussion of the problems with the RNA world hypothesis, see my book Creating Life in the Lab.)

Despite these problems, many origin-of-life researchers—including Leslie Orgel (while he was alive)—remain convinced that the RNA world scenario must be the explanation for the emergence of life via chemical evolution. Why? For one key reason: the intermediary role RNA plays in protein synthesis.

The RNA World Hypothesis

The RNA world hypothesis posits that biochemistry was initially organized exclusively around RNA and only later did evolutionary processes transform the RNA world into the familiar DNA-protein world of contemporary organisms. If this model is correct, then the DNA-protein world represents the historically contingent outworking of evolutionary history. To put it another way, contemporary biochemistry has been cobbled together by unguided evolutionary forces and the role RNA plays in protein synthesis is an accidental outcome.

The discovery of ribozymes in the 1980s provided initial support for the RNA world scenario. These RNA molecules possess functional capabilities, behaving just like enzymes. In other words, RNA not only harbors information like DNA, it also carries out cellular functions like proteins. Origin-of-life researchers take RNA’s dual capacities as evidence that life could have been organized around RNA biochemistry. These same researchers presume that evolutionary processes later apportioned RNA’s twofold capabilities between DNA (information storage) and proteins (function). Origin-of-life researchers often point to RNA’s intermediary role in protein synthesis as evidence for the RNA world hypothesis. Again, RNA’s reduced role in contemporary biochemical systems stands as a vestige of evolutionary history, with RNA viewed as a sort of molecular fossil.

Ribosomes serve as a prime illustration of RNA’s role as a go-between in protein synthesis. As subcellular particles, ribosomes catalyze (assist) the chemical reactions that form the bonds between the amino acid subunits of the proteins. Two subunits of different sizes (comprised of proteins and RNA molecules) combine to form a functional ribosome. In organisms like bacteria, the large subunit (LSU) contains 2 ribosomal RNA (rRNA) molecules and about 30 different protein molecules. The small subunit (SSU) consists of a single rRNA molecule and about 20 proteins. In more complex organisms, the LSU is formed by 3 rRNA molecules that combine with around 50 distinct proteins, and the SSU consists of a single rRNA molecule and over 30 different proteins.

The rRNA molecules function as scaffolding, organizing the myriad ribosomal proteins. They also catalyze the chain-forming reactions between amino acids. In other words, the ribosome is a ribozyme. At the ISSOL 2002 meeting, I heard Orgel adamantly insist that the RNA world hypothesis must be valid because rRNA catalyzes protein bond formation.

Orgel’s perspective gains support considering the inefficiency of ribozymes as catalysts. Protein enzymes are much more efficient than ribozymes. In other words, it seemingly would be better and more efficient to design ribosomes so that proteins catalyzed bond formation between amino acids, not rRNA. This reason convinces origin-of-life researchers that the role rRNAs play in protein synthesis is a haphazard consequence of life’s historically contingent evolutionary history.

But recent work by scientists from Harvard and Uppsala Universities paints a different picture of the compositional makeup of ribosomes, and in doing so, undermines what many origin-of-life researchers believe to be the most compelling evidence for the RNA world hypothesis. These researchers demonstrate that the compositional makeup of ribosomes does not appear to be the accidental outworking of an unguided, contingent process. Instead, an exquisite molecular logic accounts for the composition and structural properties of the protein and rRNA components of ribosomes.2

Is There a Rationale for Ribosome Structure?

As part of their research efforts, the Harvard and Uppsala University investigators were specifically trying to answer several questions related to the composition of ribosomes, including:

  1. Why are ribosomes made up of so many proteins?
  2. Why are ribosomal proteins nearly the same size?
  3. Why are ribosomal proteins smaller than typical proteins?
  4. Why are ribosomes made up of so few rRNA molecules?
  5. Why are rRNA molecules so large?
  6. Why do ribosomes employ rRNA as the catalyst to form bonds between amino acids, instead of proteins which are much more efficient as enzymes?

Ribosomes Make Ribosomes

Before a cell can replicate, ribosomes must manufacture the proteins needed to form more ribosomes—in fact, ribosomes need to manufacture enough proteins to form a full complement of these subcellular complexes. This ensures that both daughter cells have the sufficient number of protein-manufacturing machines to thrive once the cell division process is completed. Because of this constraint, cell replication cannot proceed until a duplicate population of ribosomes is produced.

Ribosome Composition is Optimal for Efficient Production of Ribosomes

As discussed in an earlier blog post, the Harvard and Uppsala University investigators discovered that if ribosomal proteins were large, or if these biomolecules were variable in size, ribosome production would be slow and inefficient. Building ribosomes with smaller, uniform-size proteins represents the faster way to duplicate the ribosome population, permitting the cell replication to proceed in a timely manner. They also determined that the optimal number of ribosomal proteins is between 50 to 80—the number of ribosomal proteins found in nature. In short, the composition of these sub cellular complexes appears to be undergirded by an elegant molecular rationale.

As part of their mathematical modeling study, these researchers also provided an explanation for why ribosomes are made up of large RNA molecules. Because the number of steps involved in rRNA production is fewer than the steps required for protein manufacture, rRNA molecules can be made more rapidly than proteins. This being the case, ribosome production is more efficient when these organelles are built using fewer and larger rRNA molecules as opposed to smaller, more numerous ones.

The research team learned that ribosomes containing more rRNA can be built faster than ribosomes made up of more proteins. This fact helps explain why rRNA operates as the catalytic portion of ribosomes (linking amino acids together to construct proteins), though less efficient as a catalyst than proteins.

These insights also explain the compositional differences among ribosomes found in bacteria, eukaryotic cells, and mitochondria. Bacteria, which typically replicate faster than eukaryotic cells, possess ribosomes that contain proportionally more rRNA and fewer proteins than ribosomes found in eukaryotic cells. Mitochondria—organelles found in eukaryotic cells—possess ribosomes with a much greater ratio of proteins to rRNA than eukaryotic cells. This observation makes sense because ribosomes in mitochondria don’t produce themselves.

It Would Be a Miracle if a Strand of RNA Appeared on the Primitive Earth

An exquisite molecular rationale undergirds the number and size of rRNA molecules in ribosomes and accounts for why the ribosome is a ribozyme. The work of the Harvard and Uppsala University scientists undermines the view that ribosomes were cobbled together as a result of the evolutionary transition from the RNA world to the DNA/protein world. If the presence and role of RNA molecules in ribosomes were simply vestiges of life’s origin out of an RNA world, then there should not be an elegant molecular logic that accounts for ribosome compositions in bacteria and eukaryotic organisms. In other words, it doesn’t appear as if ribosomes are the unintended outcome of an unguided evolutionary process.

This conclusion gains support from earlier work by life scientist Ian S. Dunn. As I wrote about in a previous blog post, Dunn has uncovered a molecular rationale for the intermediary role messenger RNA (mRNA) plays in protein synthesis. Again, it indicates that the intermediary role of RNA molecules in protein synthesis is a necessary design of a DNA/protein world, not a molecular vestige of life’s evolutionary origin that proceeds through an RNA world.

Given these new insights and the intractable problems with the RNA world scenario, I must agree with Leslie Orgel. It would be a miracle if a strand of RNA appeared on the primitive Earth—unless a Creator intervened.

Resources to Dig Deeper

Endnotes

  1. Fazale Rana, Creating Life in the Lab: How New Discoveries in Synthetic Biology Make a Case for the Creator(Grand Rapids, MI: Baker Books, 2011), 161.
  2. Shlomi Reuveni, Måns Ehrenberg, and Johan Paulsson, “Ribosomes Are Optimized for Autocatalytic Production,” Nature 547 (July 20, 2017): 293–7, doi:10.1038/nature22998.
Reprinted with permission by the author
Original article at:
https://www.reasons.org/explore/blogs/the-cells-design/read/the-cells-design/2017/11/08/ribosomes-manufactured-by-design-part-2