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Ciliate Organism Undergoes “Scrambled Genome” and “Massive…Rearrangement”

Casey Luskin

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 this 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 liquefaction 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.

Casey Luskin

Associate Director, Center for Science and Culture
Casey Luskin is a geologist and an attorney with graduate degrees in science and law, giving him expertise in both the scientific and legal dimensions of the debate over evolution. He earned his PhD in Geology from the University of Johannesburg, and BS and MS degrees in Earth Sciences from the University of California, San Diego, where he studied evolution extensively at both the graduate and undergraduate levels. His law degree is from the University of San Diego, where he focused his studies on First Amendment law, education law, and environmental law.

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