Category Archives: LUCA

An Exceedingly Exceptional Code

I’m not sure how I missed this one. Recall that only one of a million randomly generated codes was more error-proof that the genetic code used by life. Well, in turns out the frequency of amino acids used by all three domains of life is much the same. And when you factor for this frequency of amino acid use, the genetic code is actually much better than “one in a million”:

We found that taking the amino-acid frequency into account decreases the fraction of random codes that beat the natural code. This effect is particularly pronounced when more refined measures of the amino-acid substitution cost are used than hydrophobicity. To show this, we devised a new cost function by evaluating in silico the change in folding free energy caused by all possible point mutations in a set of protein structures. With this function, which measures protein stability while being unrelated to the code’s structure, we estimated that around two random codes in a billion (10^9) are fitter than the natural code. When alternative codes are restricted to those that interchange biosynthetically related amino acids, the genetic code appears even more optimal.

[Gilis D, Massar S, Cerf NJ, Rooman M. 2001. Optimality of the genetic code with respect to protein stability and amino-acid frequencies. Genome Biol. 2(11):RESEARCH0049]

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Front-loading with ribosomes

While outlining the logic of front-loading in The Design Matrix, I noted how the existence of multifunctional (moonlighting) proteins would serve the needs of front-loading. In essence, a protein with multiple functions can be viewed as a protein that is packed with preadaptations ready to be more fully exploited when the proper conditions arise.

This developing paradigm has allowed me to come up with a prediction. If evolution was front-loaded, and a significant aspect of this front-loading existed as multifunctional proteins, whereby secondary or tertiary functions could be unleashed as evolution proceeded into the future, an excellent candidate for storage of some of these secondary functions would be the ribosome, the protein-synthesizing factory of the cell. This is because a designer could count on the ribosome being retained, largely unchanged, throughout billions of years of evolution because it plays such an absolutely essential role in life. If it remains largely unchanged, secondary functions can be carried into the future. Thus, I would predict that ribosomal proteins, which normally function as chaperones to fold the ribosomal RNA and hold it together to form the functioning ribosome, would also exhibit secondary functions (moonlight).

And a survey of the literature does indeed support this prediction.

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Genomes and LUCA

Continuing our hunt for LUCA, we have “A minimal estimate for the gene content of the last universal common ancestor—exobiology from a terrestrial perspective” by Christos Ouzounis , Victor Kunin, Nikos Darzentas, and Leon Goldovsky (Research in Microbiology 157 (2006) 57–68).   This research compared 184 completed genomes from the three domains in the search for LUCA.

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Protein Domains in LUCA

Here is an abstract of a study that was published in 2006 by Juan A. Ranea, Antonio Sillero, Janet Thornton, and Christine A. Orengo (J Mol Evol 63:513–525):

By exploiting three-dimensional structure comparison, which is more sensitive than conventional sequence-based methods for detecting remote homology, we have identified a set of 140 ancestral protein domains using very restrictive criteria to minimize the potential error introduced by horizontal gene transfer. These domains are highly likely to have been present in the Last Universal Common Ancestor (LUCA) based on their universality in almost all of 114 completed prokaryotic (Bacteria and Archaea) and eukaryotic genomes. Functional analysis of these ancestral domains reveals a genetically complex LUCA with practically all the essential functional systems present in extant organisms, supporting the theory that life achieved its modern cellular status much before the main kingdom separation (Doolittle 2000). In addition, we have calculated different estimations of the genetic and functional versatility of all the superfamilies and functional groups in the prokaryote subsample. These estimations reveal that some ancestral superfamilies have been more versatile than others during evolution allowing more genetic and functional variation. Furthermore, the differences in genetic versatility between protein families are more attributable to their functional nature rather than the time that they have been evolving. These differences in tolerance to mutation suggest that some protein families have eroded their phylogenetic signal faster than others, hiding in many cases, their ancestral origin and suggesting that the calculation of 140 ancestral domains is probably an underestimate.

The discussion and data concerning the differences in genetic versatility between protein families is quite interesting, and worth discussing later, but let’s stay focused on our hunt for LUCA, a “genetically complex” group of organisms “with practically all the essential functional systems present in extant organisms.”

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The Hunt for LUCA

The Seeding Story and Spawning Story have a different story to tell. The former begins with a consortium of sophisticated, complex cells while the latter begins with a simple self-replicating molecule able to co-opt from a huge assortment of potentially useful chemicals in the thick prebiotic broth. Does it really make sense to think such two radically different starting points cannot leave any traces that would help us distinguish between the two?

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What is life? Biologists have long understood that life is very hard to nail down with any precise definition. Daniel Koshland, from the Department of Molecular and Cell Biology at the University of California, recounts the following story that nicely illustrates this:

What is the definition of life? I remember a conference of the scientific elite that sought to answer that question. Is an enzyme alive? Is a virus alive? Is a cell alive? After many hours of launching promising balloons that defined life in a sentence, followed by equally conclusive punctures of these balloons, a solution seemed at hand: “The ability to reproduce—that is the essential characteristic of life,” said one statesman of science. Everyone nodded in agreement that the essential of a life was the ability to reproduce, until one small voice was heard. “Then one rabbit is dead. Two rabbits— a male and female— are alive but either one alone is dead.” At that point, we all became convinced that although everyone knows what life is there is no simple definition of life. [Koshland, DE. 2002. The Seven Pillars of Life. Science 295: 2215-2216.]

Moving away from a reductionist definition, Koshland instead identifies seven universal principles inherent in all living things. He calls these the “pillars” of life. Since such pillars are features of life itself, and LUCA (the last universal common ancestor) would also be considered an expression of life (otherwise, it could not evolve into the three basic cell types), it seems quite reasonable to suppose that the same seven pillars would apply to LUCA. So what are they?

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