From: Astrobiology Magazine
Posted: Monday, November 10, 2008
By Michael Schirber
Heat-loving organisms live where the water is hot but the gene pool is shallow. Genetic analysis has shown that so-called thermophiles have fewer mutations in their protein-coding genes than do their microbial cousins that live at room temperature. This seems to imply that the opportunities to evolve decrease as temperature increases.
To confirm this, Jonathan Silberg of Rice University and colleagues will explore how resilient proteins are to mutations at different temperatures. The results could have implications for theories that claim life arose near hydrothermal vents.
It is not surprising that high temperatures are tough on living things. If exposed to extreme heat, most cells will die because their outer membrane becomes unstable or because essential molecules, like proteins and DNA, cease to function properly. Proteins are especially sensitive to temperature: they become denatured (i.e. change their shape) when over-heated.
"Most proteins are marginally stable at their natural environmental temperature, which is to say that they aren't all that much more stable than they need to be," says Jesse Bloom of California Institute of Technology in Pasadena, CA. "At one time, this might have been thought to imply that these proteins just couldn't get any more stable."
However, scientists have since discovered thermophilic organisms whose proteins work just fine at temperatures as high as 121 degrees Celsius (249.8 degrees Farhenheit). This begs the question: can proteins be stable at even higher temperatures? Or do thermophiles mark the temperature boundary for protein-based life?
Silberg thinks his group can answer this question by studying the potential for proteins to evolve as a function of temperature. "Our basic question is: how hard is it for Nature to design a protein at high temperature?" Silberg says.
As part of NASA's Astrobiology: Exobiology and Evolutionary Biology program, Silberg's group will compare the effects of mutations on two versions of an essential type of protein found in both thermophiles and normal temperature mesophiles.
Proteins perform a multitude of roles in living organisms. As enzymes, they help break down food; as receptors, they receive signals from other cells; as connectors, they provide structure. A single species will have many thousands of different proteins, each characterized by a sequence of amino acids linked together in a chain. These chains fold up on themselves to form a complex three dimensional shape. Often it is this shape that allows a protein to do its job. However, the shape is not uniquely tied to one chain of amino acids: there can be several different chains that all fold up into the same shape and, therefore, all do roughly the same thing.
This redundancy is thought to be crucial to the evolution of proteins because it allows for a certain amount of random mutations. Imagine an organism relies on protein X to do some vital task inside its cells. One day a mutation occurs in the gene that codes for protein X, resulting in a slightly different amino acid sequence. Two things can happen. One, the mutated protein X folds in a different way and is therefore useless. The organism ends up dying or is unfit to compete with its neighbors. The other possibility is that the mutated protein X retains the original shape and therefore continues to perform the same task as before -- a "shape-preserving mutation." Each protein has a whole network of shape-preserving mutations associated with it.
"Over time, organisms drift across these networks in order to find some slight improvement," Silberg says. Those genetic mutations that confer some advantage will spread throughout the population. "That's how adaptive evolution works," Silberg says.
In earlier work, Silberg and colleagues devised a model that predicts how many shape-preserving mutations are associated to a particular protein. The model is based on thermodynamic parameters that give the probability that a certain amino acid sequence has a particular shape.
"My idea comes from a physics perspective," Silberg says. "Proteins are polymer chains in which each bead can be one of 20 different amino acids, so what happens if you change one of the beads?"
Although most of the work is done with computer simulations, the researchers have tested the accuracy of their model by synthesizing proteins in the lab with various amino acid substitutions. The results provide a picture of the evolutionary playing field on which protein-coding genes can explore possible improvements.
Gene pool put on simmer
In this new project, Silberg's group plans to look for the first time at the number of shape-preserving mutations available to thermophiles. Their hypothesis is that the evolutionary playing field shrinks - that there are fewer possibilities for viable mutations --as the temperature goes up.
Previous work has shown that the protein-coding genes of thermophiles have an unusually low number of a particular type of mutations. The cause of this may not be due to temperature, because reduced genetic diversity can arise in a number of ways. Silberg and his collaborators want to directly examine a protein at high temperature to see if it is less tolerant to slight changes in its amino acid configuration. This experiment could confirm whether or not genetic diversity is correlated with temperature.
The protein the group has chosen to study is adenylate kinase (AK), which regulates the energy inside a cell and is essential to all living things. The researchers will look at AK in two bacteria: a thermophile (Thermus thermophilus) and a mesophile (E. coli). The AK protein is similar in both organisms, but there are distinct differences due to the fact that they operate at different temperatures (80 and 40 degrees C, respectively, (176 and 104 F)). The researchers will determine-through a combination of lab work and computer simulations-which amino acid substitutions retain the original shape of each protein at their respective temperatures. By comparing the number of shape-preserving substitutions, the team will be able to say how temperature affects protein evolution.
"The research proposed by Dr. Silberg is potentially interesting because it will indicate whether the proteins of thermophiles are anywhere near the maximum thermostability that is evolutionary achievable," says Bloom, who is not involved with this study.
If thermophilic proteins are just barely within the evolutionary limits, this might argue against hydrothermal vents and/or hot volcanic pools being home to the first life on Earth (a popular theory due to the fact that thermophiles are closely related to life's earliest common ancestor). If high temperatures prove to be less forgiving of the genetic mutations that are necessary for evolution, then it might make more sense that life started in cooler environs and only later migrated into hot places.
Furthermore, if Silberg and company do find a temperature dependence to protein mutation tolerance, the results might be extrapolated to higher temperatures to locate at what point the evolutionary playing field shrinks to zero."This will tell us where proteins no longer make for a good polymer," Silberg says. If life were to exist on an exoplanet hotter than this maximum protein temperature, those extra-terrestrials would likely need a different "do-it-all" molecule to replace proteins.
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