Competition among equals: How multicellular organisms develop
By Ruth SoRelle, M.P.H.
More than two decades ago, when Gad Shaulsky, Ph.D. was an undergraduate student, he began to puzzle over why cells become different in organisms made up of many cells. All the cells contain the same genetic code, but their outward behaviors and appearances are very different.
The mystery of differentiation – the way in which cells become different as organisms grow and develop – has fascinated scientists for years and generated a host of theories as to its rationale.
Competition determines proportion
As Shaulsky's scientific expertise grew and matured, he began to consider the various theories. At the same time, he and a friend began to think about the possibility that competition among the cells in an organism – say the human body – could contribute to this process and to the survival of the organism as a whole. In a recent essay that appeared online in the journal Nature Reviews Genetics, he and Anupama Khare, a graduate student, address the possibility that competition could determine which cells take precedence in an organism made up of many kinds of cells.
Shaulsky is an associate professor of molecular and human genetics and the program in developmental biology at Baylor College of Medicine. Khare is pursuing her graduate studies in his laboratory.
Shaulsky does not claim that the report, which not only proposes his hypothesis but also explores the competition among cells in a variety of organisms, proves his point, but he does see it as beginning the dialogue.
"What we are proposing in this paper is that evolution tinkered with what it had to work with," said Shaulsky. "It took the basic tendency of cells to compete and harnessed it to determine proportions among cells. It was something that had to happen for multicellular organisms to work.
Spore and stalk cells
He points to an example from Dictyostelium discoideum, the model organism with which he works most frequently. Dictyostelium is a single-celled organism when food is plentiful. When food supplies dwindle, they aggregate into multicellular organisms. Learn more about Dictyostelium at http://dictybase.org/tutorial/.
Dictyostelium has both spore and stalk cells. Spore cells are alive, and stalk cells are dead. A killer gene was introduced into the cells that were "pre-spore."
What the scientists found buttressed Shaulsky's competitive premise. The pre-stalk cells "transdifferentiated" to replace the dying pre-spore cells that were crucial to the organism's survival. However, if the scientists killed the pre-stalk cells, the pre-spore cells did not change to replace them because they were not critical to survival.
"Once the pre-spore cells were established, those that were left became pre-stalk but they maintained the ability to become pre-spore," he said. The finding showed the ability to become "pre-spore" had been harnessed to maintain the balance between tissue types.
Biological imperatives
"If you look at the life of unicellular organisms, there is no question. They compete and the fittest survive," said Shaulsky. However, multicellular organisms represent a paradox because they are a collection of individual cells.
"Some of these individual cells give up the two most important tendencies in biology – survival and reproduction," he said. "In our body, most cells will not survive. They are being replaced constantly. Most will not reproduce."
Giving up these biological imperatives is a requirement of multicellularity because cells must execute different functions so not all of them can participate in reproduction.
Evolutionary perspective
What defines a unit of evolutionary selection?" he asked. "Why should we think there is no competition among genetically identical cells in the body in which the best cells will give rise to the germ line (sperm and eggs) and the next best cells will give rise to the progenitor (or stem) cells that keep renewing themselves and give rise to the more differentiated tissues of the body? The least fit cells will be those that eventually die, such as red blood cells, skin or hair."
"From an evolutionary perspective, it made sense to us," he said. "Competition is one of the strongest forces in biology. It didn't make sense to us that these tendencies would be wiped out upon transition from unicellular to multicellular organisms. They might be harnessed to serve other purposes, but they would still be there."
The notion is not strange to scientists who study how organisms develop, but it runs contrary to the thought of most evolutionary biologists, he said. "Evolutionary biology says that competition happens to a point. The cost of competition is high and, from an evolutionary perspective, when organisms are genetically identical, they don't compete," he said. "We say, yes, they do compete and we give examples."
In the essay, Khare and Shaulsky find examples of competition in a variety of creatures – from the soil amoeba Dictyostelium discoideum that vacillates between unicellular and multicellular depending on external conditions to Drosophila melanogaster or fruit flies to mice and humans.
"What we are proposing is that evolution tinkered with what it had to work with," said Shaulsky. "It took the basic tendency of cells to compete and harnessed it to serve in developmental decision making processes. It was something that had to happen for multicellular organisms to work."
The work should bridge the gap between the two kinds of biologists, he said. "Developmental biologists should look at processes they are studying from the point of view of what is the evolutionary advantage of this competitive process. And evolutionary biologists could benefit from revisiting their notion that identical units don't compete."
