Singled-celled eukaryotic organisms known as Tetrahymena contain many features that make them a good candidate model for front-loading evolution. At first glance, there does not seem to be anything all that special about them. They are pear-shaped protozoa that are widely distributed around the globe, mainly found in freshwater. Their lifestyle is predatory, where they will eat just about any organic substance they come into contact with. And their cell surface is covered with cilia, reflecting the fact that they are closely related to Paramecia, a protozoan that is familiar to all first-year biology students.

Several years ago, I noted one feature of Tetrahymena that helped us approach evolution through the perspective of front-loading: the elimination of histone protein H1 does not seem to have any deleterious effect in this protozoan, while H1 is essential in a complex metazoan state. While I will not expand on this story, it turns out Tetrahymena has more to offer when it comes to helping us envision the front-loading and design of evolution.

Another feature that is seen in the ciliates such as Tetrahymena which also speaks to the plausibility of front-loading centers around the fact that these single-celled creatures actually possess two nuclei. One nucleus, known as the micronucleus (MIC), contains a standard diploid set of five distinct chromosomes. The MIC is dormant most of the time as Tetrahymena swim about and look for food. However, when it is time to reproduce, the nucleus undergoes meiosis and forms a haploid state which can then be fused with another haploid MIC (in an event known as conjugation) to produce a new cell and corresponding diploid state.

The second nucleus is known as the macronucleus (MAC) and is derived and differentiated from mitotic copies of the MIC after reproduction. The MAC is in charge of the basic house-keeping duties of the cell, as it expresses all the genes needed for the everyday life of this protozoan. How does this speak to front-loading? What has been packaged into a single-cell is nothing less than the metazoan theme of somatic cells (MAC) and germline (MIC)!

The genome of Tetrahymena thermophila has been recently sequenced [1] and the new information adds to the plausibility of front-loading and the design of evolution. Here is a brief synopsis of some of the findings.

1. MAC differentiation entails the activation of programmed DNA rearrangements and the amplification of chromosome number. What is most interesting is that this DNA processing involves a pathway that cuts away much of the “junk DNA” that is part of the MIC. In fact, the researchers estimate that 90-100% of repetitive DNA is excised during MAC differentiation. Also removed are most of the transposon sequences.

Tetrahymena thus has the machinery and ability to “cleanse” itself of most of the genomic “junk.” But it doesn’t. Instead, it sequesters the “junk” into the germline. Given the role that sexual reproduction already plays in evolvability, it is tempting to speculate that Tetrahymena are telling us that “junk DNA” serves a very useful role, but it is a role that is restricted to reproduction and evolution.

2. Tetrahymena is the only known organism that can apparently assign an amino acid to each of its 64 codons. According to the canonical code, three codons are assigned to role of termination. In Tetrahymena, two of those codons actually signal for the incorporation of the amino acid glutamine. The third termination codon, UGA, does signal for termination, but can also be used in a context-dependent manner (depending on RNA structure) to code the amino acid, selenocysteine. What does this tell us? The genetic code can evolve. It is not a frozen accident. The fact that the code can indeed evolve makes its original universality all the more suggestive of design. More on that later.

3. The genome of Tetrahymena shows impressive examples of massive expansion of gene families by gene duplication. This, in turn, speaks to the design potential that is built into many of life’s core genes. For example, consider the kinases, which are enzymes that function to attach phosphate groups to other proteins giving the kinases the ability to modulate the activity of entire signaling circuits that coordinate and control intracellular activity. Tetrahymena have almost 1000 different kinases all serving the needs of a single cell. These kinases represented 54 of the known families (and subfamilies) of kinases. Also, there are 37 classes of kinases that are thus far unique to Tetrahymena. As the researchers comment:

The presence of so many novel kinases and expansions is both an indication of the versatility of the eukaryotic protein kinase domain seen in other lineages and suggestive of a great elaboration of ciliate-specific functions.

On one hand, it could have been simply good luck that the Blind Watchmaker stumbled upon a domain that would prove to be so useful and versatile. On the other hand, we might be looking at the echo of a wise, front-loading design.

4. I saved the best for last. The genome of Tetrahymena encodes for 27,424 protein-coding genes. In comparison, baker’s yeast have only 6500 such genes, fruit flies have about 14,000, and humans have close to 36,000 genes. In other words, this single-celled organism uses almost twice the number of proteins than the entire fruit fly and comes awfully close to the gene count for human beings.

Single-celled organisms can thus be stuffed with tens of thousands of genes that will be propagated over great spans of time.

Even more interesting is that many of these extra genes are probably ancient:

The high gene count in T. thermophila relative to some other single-celled eukaryotes is not simply a reflection of gene family expansions. For example, when recent gene expansions are collapsed into ortholog sets, we find that humans and T. thermophila share more orthologs with each other (2,280) than are shared between humans and the yeast S. cerevisiae (2,097) or T. thermophila and P. falciparum (1,325) (Figure 6), despite the sister phyla relationships of animals and fungi on the one hand and ciliates and apicomplexans on the other. We note that this does not mean that humans and T. thermophila are overall more similar to each other than either is to species in sister phyla. For example, humans and S. cerevisiae do share some processes that evolved in the common ancestor of fungi and animals. In addition, for orthologs found in all eukaryotes, the human and S. cerevisiae genes are more similar in sequence to each other than either is to genes from T. thermophila. The higher number of orthologs shared between humans and T. thermophila is a reflection of both the loss of genes in other eukaryotic lineages and the retention of a variety of ancestral eukaryotic functions by T. thermophila. Consistent with this conclusion, there are 874 human genes with orthologs in T. thermophila but not S. cerevisiae, 58 of which correspond to loci associated with human diseases (Table S12). Thus genome analysis reveals many cases where T. thermophila can continue to complement experimental studies of yeast as a model system for eukaryotic (and human) cell biology [13].

ScienceDaily summarizes as follows:

Although the organism is single-celled, it contains a genetic repertoire of seemingly more complex organisms. It shares, with humans and other animals, many genes and processes typically absent in single-celled organisms. [2]

It is this type of unusual discovery that is predicted by front-loading. As Krauze explained over at Telic Thoughts:

Last year, I wrote: “I’ll make a bold prediction: Once we start sequencing the oldest branches of our family tree, we will see that we have inherited more of our complexity from the microcopes [sic] than previously thought.” This prediction flows naturally from my thoughts about front-loading - the conjecture that the first organisms were designed with a future state in mind. So, if the first eukaryotes (a large group of organisms, which includes plants, animals, fungi, and several one-celled organisms) were front-loaded for multicellularity, we would expect them to contain genes required for multicellular life.

Because front-loading predicts such deep homology, it makes a practical prediction - as we sequence the genomes of about more and more exotic protozoa, we will uncover cells that will serve as useful models for understanding various human diseases. With Tetrahymena, many of the genes shared by this protozoan and humans (but not shared by humans and fungi) have already been implicated in human diseases.

Let me close with another quote from the ScienceDaily article that underscores the potential of Tetrahymena as a working model to think about front-loading evolution:

Rather than dividing labor into several types of cells, as humans and other multicellular organisms do, T. thermophila divides its activities, either into different places inside a cell or by changing the cell over time. It is a master multi-tasker.

“This organism is a true generalist,” says evolutionary biologist Jonathan A. Eisen, who led the Tetrahymena project while at The Institute for Genomic Research (TIGR) and is now at the University of California, Davis. “Whatever this unicell touches with its hairlike projections, it will try to eat. If it does not bump into anything, the organism will seek out food with diverse sensory systems. It can protect itself from radiation and other threats and also can fight back against competitors and predators. In short, versatility is its strength. Now, we can understand how this versatility works.” [2]

1. Macronuclear Genome Sequence of the Ciliate Tetrahymena thermophila, a Model Eukaryote

2. What’s Shaped Like A Pear And Has 2 Genomes? Check The Pond