Which came first...?

What Chaperone Proteins Know

Evolution News & Views September 7, 2012 5:28 A.M

 

Here's a riddle for you: Proteins are used to make proteins, so if we assume a purely naturalistic origin of life, where did the first proteins come from?

If a cell is a factory, proteins are the factory workers. Proteins conduct most of the necessary functions in a cell. Proteins are made up of amino acid building blocks. A chain of amino acids must fold into the appropriate three-dimensional structure so that the protein can function properly. Within cells are proteins known as chaperones that help fold the amino acid chain into its proper three-dimensional structure. If the amino acid chain folds improperly, then this could wreak havoc on the cell and potentially the entire organism. The chaperone works to prevent folding defects and is a key player in the final steps of protein synthesis.

However, as important as chaperones are, there are still many questions as to how exactly they work. For example, do the chaperones fold the amino acid chain while it is still being constructed (during translation), or is the amino acid chain first put together, and then the folding beings? Or, is it some combination of both? Studies indicate that it is indeed a combination of both. There are two different kinds of chaperone proteins within the cell, one for translation and one for post-translation. With these two different kinds of chaperones, where and how does regulation happen to prevent misfolds?

Recent research on bacterial cells sheds light on the chaperones' important function. One chaperone in particular, Trigger Factor, plays a key role in correcting misfolds that may occur early on in the translational process. Trigger Factor can slow down improper amino acid folding, and it can even unfold amino acid chains that have already folded up incorrectly.

Here are some of the neat features of Trigger Factor:

• Trigger Factor actually constrains protein folding more than the ribosome does. It doesn't just "get in the way" like the ribosome. It also regulates the folding.
• Trigger Factor's function is specific to the particular region of the amino acid chain. It does not just perform one function no matter what the composition of the amino acid chain. It changes based on the region of the chain it is working with.
• Trigger Factor also changes its activity based on where the protein is in the translation process.
• Trigger Factor's process depends on how the amino acid chain is bound to the ribosome, and can even unfold parts of the chain that were misfolded in the translation process.

An additional factor that regulates when amino acid chains fold into proteins is its distance from the ribosome (the place where the amino acid chain is made). The closer the chain is to the ribosome, the less room it has to fold into a three-dimensional protein. Trigger Factor works with this spatial hindrance, making an interesting and complex regulation system.

Trigger Factor is only called into the game once the amino acid chain is a certain length (around 100 amino acids long) and when the chain has certain features, such as hydrophobicity. As the authors state it, Trigger Factor keeps the protein from folding into its three-dimensional structure until the amino acid chain has all of the information it needs to fold properly:

In summary, we show that the ribosome and TF each uniquely affect the folding landscape of nascent polypeptides to prevent or reverse early misfolds as long as important folding information is still missing and the nascent chain is not released from the ribosome.

So we have a protein that is able to perform various functions that inhibit or slow protein folding until the amino acid has the right chemical information for folding to occur.

This does not solve the riddle about proteins being made from proteins (otherwise known as the chicken-and-the-egg problem). It actually adds another twist to the riddle: How does one protein know how much information a completely different protein needs to fold into a three dimensional structure? How does a protein evolve the ability to "know" how to respond to specific translational circumstances as Trigger Factor does?

Why the search for a simple lifeform is a fool's errand.

Ciliate Organism Undergoes "Scrambled Genome" and "Massive...Rearrangement"

Casey Luskin October 14, 2014 3:39 A.M

 

 

 A fascinating new paper in the journal Cell, "The Architecture of a Scrambled Genome Reveals Massive Levels of Genomic Rearrangement during Development," describes how a unique single-celled eukaryotic organism, Oxytricha trifallax, scrambles and then reassembles its own genome as the organism reproduces. According to a story about the paper over at Princeton University's news desk:

The pond-dwelling, single-celled organism Oxytricha trifallax has the remarkable ability to break its own DNA into nearly a quarter-million pieces and rapidly reassemble those pieces when it's time to mate... The organism internally stores its genome as thousands of scrambled, encrypted gene pieces. Upon mating with another of its kind, the organism rummages through these jumbled genes and DNA segments to piece together more than 225,000 tiny strands of DNA. This all happens in about 60 hours.

One of the paper's lead researchers points out something that would occur to most any reader: "People might think that pond-dwelling organisms would be simple, but this shows how complex life can be, that it can reassemble all the building blocks of chromosomes." That kind of changes the meaning of the insult "Pond-scum"!

This ciliate organism is strange in other ways, as its cell contains two nuclei. One, called the somatic macronucleus (MAC), is used like a typical eukaryotic cell's functioning nucleus -- to generate proteins and function kind of like a CPU. But the second nucleus, called the germline micronucleus (MIC), is used to store genetic material that will be passed on to offspring during reproduction. And it's in the second nucleus that all the rearrangement and scrambling of the genome takes place.

The reproductive process of these organisms is also very strange. They don't use sex to reproduce, whether by binary fission or by creating a "new" organism. Rather, when two members of this species have "sex," they only exchange DNA for the purpose of replacing old, broken down genes. This allows them to "replace aging genes with new genes and DNA parts from its partner." Though the genome of the organism is reborn with each new generation, the organism itself is essentially immortal. The process goes approximately like this:

First the information in the second nucleus (the germline micronucleus) is broken into about 225,000 small fragments. Next, the organism swaps about half of that DNA with its mate. Then, the organism reassembles its thousands of chromosomes in the germline micronucleus. And this reassembly process shows the important functionality of non-coding DNA: "millions of noncoding RNA molecules from the previous generation direct this undertaking by marking and sorting the DNA pieces in the correct order." After sex, the old somatic macronucleus disintegrates, and a new somatic micronucleus is created from a copy of the newly assembled germline micronucleus. The paper describes the process:

In the micronucleus (MIC), macronuclear destined sequences (MDSs) are interrupted by internal eliminated sequences (IESs); MDSs may be disordered (e.g., MDS 3, 4, and 5) or inverted (e.g., MDS 4). During development after conjugation [sex], IESs, as well as other MIC-limited DNA, are removed. MDSs are stitched together, some requiring inversion and/or unscrambling. Pointers are short identical sequences at consecutive MDS-IES junctions. One copy of the pointer is retained in the new macronucleus (MAC). The old macronuclear genome degrades. Micronuclear chromosome fragmentation produces genesized nanochromosomes (capped by telomeres) in the new macronuclear genome. DNA amplification brings nanochromosomes to a high copy number.

Obviously this is an incredibly complex process, which requires numerous carefully orchestrated cellular subroutines. In fact, don't miss the paper's reference to the term "pointer." That's a term from computer science, where a pointer is a computer programming element that tells a computer where to put some piece of information. In a similar way, these ciliate organisms use pointers tell the organism where to put some piece of DNA information when it reassembles the genome.

"Radical Genome Architecture"

If that sounds complicated, consider some of the details reported in the paper about the germline micronucleus (MIC). In fact, the big story here is that this research represents the first attempt to decipher what's going on in the germline micronucleus. According to the paper, the MIC contains "over 225,000 [DNA] segments, tens of thousands of which are complexly scrambled and interwoven," where, "Gene segments from neighboring loci are located in extreme proximity to each other, often overlapping." The paper puts it this way:

The germline genome is fragmented into over 225,000 precursor DNA segments (MDSs) that massively rearrange during development to produce nanochromosomes containing approximately one gene each.

These nanochromosomes come in two types: scrambled and unscrambled. They thus further find:

In addition to the intense dispersal of all somatic coding information into >225,000 DNA fragments in the germline, a second unprecedented feature of the Oxytricha MIC genome is its remarkable level of scrambling (disordered or inverted MDSs). The germline maps of at least 3,593 genes, encoded on 2,818 nanochromosomes, are scrambled. No other sequenced genome bears zthis level of structural complexity.

They describe a striking example of scrambling: "The most scrambled gene is a 22 kb MIC locus fragmented into 245 precursor segments that assemble to produce a 13 kb nanochromosome encoding a dynein heavy chain family protein." But the complexity of the germline micronucleus goes even deeper, as some of the scrambled genes entail genes encoded within genes:

A third exceptional feature we noted is 1,537 cases (1,043 of which are scrambled) of nested genes, with the precursor MDS segments for multiple different MAC chromosomes interwoven on the same germline locus, such that IESs for one gene contain MDSs for another.

Additionally, these precursor DNA sequences may encode multiple chromosomes in the somatic macronucleus, which are shuffled and spliced back together during the reassembly process:

A fourth notable feature arising from this radical genome architecture is that a single MDS in the MIC may contribute to multiple, distinct MAC chromosomes. Like alternative splicing, this modular mechanism of "MDS shuffling" ... can be a source of genetic variation, producing different nanochromosomes and even new genes and scrambled patterns. At least 1,267 MDSs from 105 MIC loci are reused, contributing to 240 distinct MAC chromosomes. A single MDS can contribute to the assembly of as many as five different nanochromosomes.

There's a lot more in this paper discussing the complexity of these processes that deconstruct and reassemble the genome of Oxytricha trifallax. The natural question that arises is "How did this evolve?" The paper doesn't even attempt to offer an answer -- it's simply descriptive.

In a way, the degradation and reassembly of the genome brings to mind the liquidation and rebuilding of an insect's body during holometabolism. For more on that, see the Illustra film Metamorphosis. Holometabolism has also baffled evolutionary biologists since the programming for the entire process must be fully in place before it occurs, or you end up with a dead organism. Given the importance of a genome to an organism's survival, one would expect the same to be true of the processes involved in the degradation and reassembly of the Oxytricha trifallax genome.
From the perspective of intelligent design, these complex processes are more readily accounted for. They require a cause capable of thinking ahead, with planning and foresight. Intelligent agency is capable of doing that. An intelligent agent could produce the information to program the process of deconstructing and reassembling the Oxytricha trifallax genome from the beginning.

A goal-directed creative process like ID can shed light on the mystery of the Oxytricha trifallax genome. Obviously this paper in no way suggests that ID is the answer. But something tells me that unguided evolutionary explanations of the genomic complexity reported by these researchers won't be forthcoming.

 

Things that make you say "hmmm."

Doctor Doom, Eric Pianka, Receives Standing Ovation from Texas Academy of Science

Jonathan Witt April 3, 2006 3:15 P 

 

 

The following is excerpted from "Meeting Doctor Doom" by Forrest Mims, Chairman of the Environmental Science Section of the Texas Academy of Science:

... I watched in amazement as a few hundred members of the Texas Academy of Science rose to their feet and gave a standing ovation to a speech that enthusiastically advocated the elimination of 90 percent of Earth's population by airborne Ebola. The speech was given by Dr. Eric R. Pianka (Fig. 1), the University of Texas evolutionary ecologist and lizard expert who the Academy named the 2006 Distinguished Texas Scientist. Something curious occurred a minute before Pianka began speaking. An official of the Academy approached a video camera operator at the front of the auditorium and engaged him in animated conversation. The camera operator did not look pleased as he pointed the lens of the big camera to the ceiling and slowly walked away.
This curious incident came to mind a few minutes later when Professor Pianka began his speech by explaining that the general public is not yet ready to hear what he was about to tell us.

Because of many years of experience as a writer and editor, Pianka's strange introduction and the TV camera incident raised a red flag in my mind. Suddenly I forgot that I was a member of the Texas Academy of Science and chairman of its Environmental Science Section. Instead, I grabbed a notepad so I could take on the role of science reporter. One of Pianka's earliest points was a condemnation of anthropocentrism, or the idea that humankind occupies a privileged position in the Universe. He told a story about how a neighbor asked him what good the lizards are that he studies. He answered, "What good are you?"
Pianka hammered his point home by exclaiming, "We're no better than bacteria!"
Pianka then began laying out his concerns about how human overpopulation is ruining the Earth. He presented a doomsday scenario in which he claimed that the sharp increase in human population since the beginning of the industrial age is devastating the planet. He warned that quick steps must be taken to restore the planet before it's too late.
Saving the Earth with Ebola
Professor Pianka said the Earth as we know it will not survive without drastic measures. Then, and without presenting any data to justify this number, he asserted that the only feasible solution to saving the Earth is to reduce the population to 10 percent of the present number.
He then showed solutions for reducing the world's population in the form of a slide depicting the Four Horsemen of the Apocalypse. War and famine would not do, he explained. Instead, disease offered the most efficient and fastest way to kill the billions that must soon die if the population crisis is to be solved.
Pianka then displayed a slide showing rows of human skulls, one of which had red lights flashing from its eye sockets.
AIDS is not an efficient killer, he explained, because it is too slow. His favorite candidate for eliminating 90 percent of the world's population is airborne Ebola ( Ebola Reston ), because it is both highly lethal and it kills in days, instead of years. However, Professor Pianka did not mention that Ebola victims die a slow and torturous death as the virus initiates a cascade of biological calamities inside the victim that eventually liquefy the internal organs.
After praising the Ebola virus for its efficiency at killing, Pianka paused, leaned over the lectern, looked at us and carefully said, "We've got airborne 90 percent mortality in humans. Killing humans. Think about that."
With his slide of human skulls towering on the screen behind him, Professor Pianka was deadly serious. The audience that had been applauding some of his statements now sat silent.
After a dramatic pause, Pianka returned to politics and environmentalism. But he revisited his call for mass death when he reflected on the oil situation.
"And the fossil fuels are running out," he said, "so I think we may have to cut back to two billion, which would be about one-third as many people." So the oil crisis alone may require eliminating two-third's of the world's population.
How soon must the mass dying begin if Earth is to be saved? Apparently fairly soon, for Pianka suggested he might be around when the killer disease goes to work. He was born in 1939, and his lengthy obituary appears on his web site.
When Pianka finished his remarks, the audience applauded. It wasn't merely a smattering of polite clapping that audiences diplomatically reserve for poor or boring speakers. It was a loud, vigorous and enthusiastic applause.
Questions for Dr. Doom
Then came the question and answer session, in which Professor Pianka stated that other diseases are also efficient killers.
The audience laughed when he said, "You know, the bird flu's good, too." They laughed again when he proposed, with a discernable note of glee in his voice that, "We need to sterilize everybody on the Earth."
After noting that the audience did not represent the general population, a questioner asked, "What kind of reception have you received as you have presented these ideas to other audiences that are not representative of us?"
Pianka replied, "I speak to the converted!"
Pianka responded to more questions by condemning politicians in general and Al Gore by name, because they do not address the population problem and "...because they deceive the public in every way they can to stay in power."
He spoke glowingly of the police state in China that enforces their one-child policy. He said, "Smarter people have fewer kids." ...
With this, the questioning was over. Immediately almost every scientist, professor and college student present stood to their feet and vigorously applauded the man who had enthusiastically endorsed the elimination of 90 percent of the human population. Some even cheered. Dozens then mobbed the professor at the lectern to extend greetings and ask questions. It was necessary to wait a while before I could get close enough to take some photographs (Fig. 1).
I was assigned to judge a paper in a grad student competition after the speech. On the way, three professors dismissed Pianka as a crank. While waiting to enter the competition room, a group of a dozen Lamar University students expressed outrage over the Pianka speech.
Yet five hours later, the distinguished leaders of the Texas Academy of Science presented Pianka with a plaque in recognition of his being named 2006 Distinguished Texas Scientist. When the banquet hall filled with more than 400 people responded with enthusiastic applause, I walked out in protest.
Corresponding with Dr. Doom
Recently I exchanged a number of e-mails with Pianka. I pointed out to him that one might infer his death wish was really aimed at Africans, for Ebola is found only in Central Africa. He replied that Ebola does not discriminate, kills everyone and could spread to Europe and the the Americas by a single infected airplane passenger.
In his last e-mail, Pianka wrote that I completely fail to understand his arguments. So I did a check and found verification of my interpretation of his remarks on his own web site. In a student evaluation of a 2004 course he taught, one of Professor Pianka's students wrote, "Though I agree that convervation [sic] biology is of utmost importance to the world, I do not think that preaching that 90% of the human population should die of ebola [sic] is the most effective means of encouraging conservation awareness." (Go here and scroll down to just before the Fall 2005 evaluation section near the end.)
Yet the majority of his student reviews were favorable, with one even saying, " I worship Dr. Pianka."
The 45-minute lecture before the Texas Academy of Science converted a university biology senior into a Pianka disciple, who then published a blog that seriously supports Pianka's mass death wish.
Dangerous Times
Let me now remove my reporter's hat for a moment and tell you what I think. We live in dangerous times. The national security of many countries is at risk. Science has become tainted by highly publicized cases of misconduct and fraud.
Must now we worry that a Pianka-worshipping former student might someday become a professional biologist or physician with access to the most deadly strains of viruses and bacteria? I believe that airborne Ebola is unlikely to threaten the world outside of Central Africa. But scientists have regenerated the 1918 Spanish flu virus that killed 50 million people. There is concern that small pox might someday return. And what other terrible plagues are waiting out there in the natural world to cross the species barrier and to which scientists will one day have access?
Meanwhile, I still can't get out of my mind the pleasant spring day in Texas when a few hundred scientists of the Texas Academy of Science gave a standing ovation for a speaker who they heard advocate for the slow and torturous death of over five billion human beings. ...