Seattle Local Health Guide Blog published an interview about our recent paper “Niche adaptation by expansion and reprogramming of general transcription factors”.
Researchers at Seattle’s Institute for Systems Biology (ISB) have discovered how a group of organisms that thrive in places with conditions that would kill most living things —such as hot springs, geysers, and salt ponds — rapidly adapt to changing conditions.
The trick, the researchers report, is the organisms’ ability to alter the activity of a group of proteins that, in turn, rapidly reset many of the organisms’ functions simultaneously.
These proteins, called general transcription factors, have long been thought to operate primarily in the background, playing a quiet, supporting role in the process of gene expression.
But new findings suggest these factors play a more important regulatory function than previously though and a fundamental role in evolution, says Nitin Baliga, Ph.D., director of Integrative Biology at the institute, who led the research team.
The paper was published online by the journal Molecular Systems Biology.
The findings not only shed light on how living things evolve, they may also help increase our understanding of the role that the human counterparts of these factors play in human health and disease, says the paper’s lead author ISB research scientist Serdar Turkarslan.
The focus of the Seattle team’s study was Halobacterium salinarum, a microscopic, single-celled organism that can thrive in super-salty environments like the the Great Salt Lake and the Dead Sea and even in salt evaporation ponds. These are the organisms that give such high-salt waters their sometimes pinkish tinge.
H salinarum belong to a group of organisms often called extremophiles (extreme + loving), because members of this group are found living in extreme environments.
Indeed, these organisms can live in water ten-times saltier than the sea, in temperatures as high as 235 degrees F (113 C), and in highly acidic conditions with a pH as low as zero.They are also found in oxygen-poor environments such as deep-sea sediments — and the human gut.
Halobacterium salinarum are from a group of extremophiles called archaea.
Although the archaea were first discovered in the 1970s in extreme environments, they have been found in many environments, and it is estimated that they make up about 20 percent of the earth’s biomass.
The archaea were originally grouped with the bacteria, but now are considered to be their own unique group because they have a different evolutionary history and a unique biochemistry.
Like bacteria, they lack nuclei, but the way they process the genetic information encoded in their DNA more closely resembles the processes seen in eukaryotes, including humans. “They look like bacteria,” says Baliga, “but they are in many ways simplified eukaryotic cells”
This makes them interesting organisms to study, Baliga says: because they are simple, they are easy to grow and tinker with; but because their molecular machinery more closely resembles that of eukaryotes, studying them can provide better insights into the molecular biology of eukaryotic, including human, cells.
Transcription Factor B
The proteins in these cells Baliga and his team were interested are a group of proteins called general transcription factors, in particular transcription factor B, or TFB.
These factors affect the activity of hundreds, even thousands of other genes, so a change in their function can have a widespread effect throughout a cell.
What was particularly interesting to the ISB researchers was that the archaea had so many copies of TFB genes, up to eleven. “Researchers wondered if only one copy was necessary, what are the other copies doing?’ Baliga said.
In addition, not only were the curiously large number of TFB genes, there also seemed to be a clear pattern to their evolution: Archaea that live in high temperature environments, for example, appeared to develop one set or “lineage” of TFBs , while those that are able to live in low oxygen environments another, and those that live in saline environments yet another.
It appeared that in Archaea, at least, TFBs doing more than just playing a quiet, supporting role in the background. “It was an observation that was hard to ignore,” says Baliga.
By tracing the family tree of the archaea, researchers have worked out that the organisms had accumulated TFB genes through a process called duplication.
Duplication is a common way cells create new genes. Indeed, about 90 percent of the genes in our chromosomes arose through duplication.
In this process, an organism makes an extra copy of a gene. Now, with two copies of the gene, it is possible for one of the copies to mutate without harming the cell.
The cell survives because, as one copy mutates, the other copy continues to do the gene’s original job. With time and chance the mutating gene can evolve to a new form that gives the organism a new ability.
“For some period of time, the genes would have the same function,” says Baliga. “But one gene can mutate as long as there is a second copy that continues to do the gene’s original tasked function. And, voila, eventually you have two genes that came from the same original gene that now have two functions.”
If that new function allows the cell to adapt to a change in the environment, say it allows the cell to handle higher temperatures, the organism now has an advantage over cells that do not have the new gene and is more likely to survive in a hotter environment.
What is Systems Biology?
“Systems biology is the study of an organism, viewed as an integrated and interacting network of genes, proteins and biochemical reactions which give rise to life. Instead of analyzing individual components or aspects of the organism, such as sugar metabolism or a cell nucleus, systems biologists focus on all the components and the interactions among them, all as part of one system.”
From the ISB Intro to Systems Biology more…
In the new study, Baliga and his colleague wanted to find out what role the different TFB genes might play in helping in H salinarum adapt to different environments.
So what they did was grow the cells in different conditions, varying the temperature, salinity and concentration of copper, a potentially toxic element in high enough concentrations.
Cells that grew better in one environment were deemed to be more “fit” for that environment than those that did not.
Then, using the systems biology approach, the team measured the activity of the different TFB genes in the different conditions and the effect they had on other genes and proteins throughout the cell.
They also tinkered with the cells, sometimes removing the genes for different TFBs, sometimes inserting genes, and repeating the experiments to see what effect the loss or addition of a particular TFB had on the cell’s “fitness”.
All in all they ran nearly 2,500 experiments, generating millions of data points on gene expression, protein activity and other factors, which they then analyzed using powerful computer algorithms.
What they found was that the different TFBs, either alone or in combination, did, indeed, allow the cells to better survive in radically different environments. In some environments, one TFB or a combination of TFBs, was crucial. In other environments, and another set of factors was important.
Expanded genetic “toolbox”
The findings suggest that by having several types of TFBs, the archaea have on hand in their genetic “toolbox” the means to quickly adjust to a variety of new conditions.
“The result is a simple, efficient way for these cells to rapidly acclimate to a changing environment,” says Baliga. “It gives them the flexibility to adapt.”
In nature, this means in a population of archaea living in a salt pond that suddenly begins to dry up and become more salty, some of the cells are more likely to have a mutated version of a TFB on hand that will allow the cells to adjust and survive in the new environment. Subsequent generations would then be able to evolve even more to be even better adapted to the new environment.
The findings not only shed light on a “fundamental mechanism of evolution”, says Baliga, it gives us insight into the biology of a the archaea, a class of organisms that makes up a substantial, if little understood part of life on earth.
Baliga says that one of the first practical uses of the research may be to engineer artificial TFBs that would make it possible for archaea to survive in highly toxic environments, such as that created by a toxic spill, where the organisms could break down the toxins and render them harmless.
The archaea could also be used as models in research into the roles TFBs play in a wide variety of human diseases, including heart disease, cancer, and a number of inherited conditions, Baliga said.
To learn more:
- http://mylocalhealthguide.com/wp-content/themes/wp-davinci_basic/images/…); background-attachment: initial; background-origin: initial; background-clip: initial; background-color: initial; background-position: 0px 1px; background-repeat: no-repeat no-repeat; “>Read Baliga and Turkarslan’s paper: Niche adaptation by expansion and reprogramming of general transcription factors.
- http://mylocalhealthguide.com/wp-content/themes/wp-davinci_basic/images/…); background-attachment: initial; background-origin: initial; background-clip: initial; background-color: initial; background-position: 0px 1px; background-repeat: no-repeat no-repeat; “>Visit the Institute for Systems Biology’s website.