Developmental Biology, Evolutionary Biology
University of California, Berkeley
Dr. King is also a professor of molecular and cell biology at the University of California, Berkeley.
Choanoflagellates and the Origin of Animals
Influenced by her father, a historian, and enthralled by the fossilized sharks' teeth and manatee bones she and her brother collected from creek beds near their Florida home, Nicole King became hooked on evolution at an early age.
"I learned that Earth's history is long and deep, and the Earth has changed," says King, an evolutionary biologist at the University of California, Berkeley. "By studying the past we can learn something about how life has evolved and how things work today."
She's fascinated by the leap, more than 600 million years ago, from single-celled life to the first multicellular animals, an event that eventually sparked the rise of all animals, including humans. There is no fossil record of these multicelled pioneers, but King says they very likely resembled a group of single-celled organisms called choanoflagellates, which are abundant today in marine and fresh water environments all over the world. "Choanos," as King fondly refers to them, generally live as single cells, but at times they can develop into colonies that resemble early-stage animal embryos.
The idea that choanoflagellates might illuminate the transition to multicellularity was proposed in the 1840s, but molecular biologists completely ignored the simple organisms, according to King, who first learned about the creatures in graduate school at Harvard University. She became convinced that choanoflagellates could unlock important secrets of the past, but there were no molecular tools to study them. So she took it upon herself to develop the tools to look for molecules and pathways that choanoflagellates share with multicellular animals, also known as metazoans.
For her postdoctoral research, she joined the University of Wisconsin–Madison lab of Sean B. Carroll (then an HHMI investigator, now HHMI vice president for science education), who was intrigued by King's unconventional and ambitious proposal. She staked her research program on being able to get the microscopic organisms to reliably form colonies in the lab for study. For a long time, the finicky protists refused to cooperate.
Fortunately, King stumbled on the solution, and in doing so, gained an unexpected insight into the evolution of multicellularity. Because choanoflagellates are grown in the presence of prey bacteria, she and her lab group at Berkeley first treated her cultures with antibiotics to reduce the amount of bacterial DNA. "Suddenly and unexpectedly," she says, "we observed tons of colony formation."
The antibiotics killed off one species of bacteria and gave another an opportunity to thrive alongside the choanoflagellates. Boosting the population of that second species triggered colony formation.
"We know that the first animals evolved in a sea of bacteria," she says. "So it's possible that the earliest animals might have developed multicellularity in response to chemical cues produced by bacteria." In recent work, she's shown that the colony-inducing bacteria produce a lipid, RIF-1, that provokes the choanoflagellates to undergo a special kind of cell division that allows them to develop into colonies.
In the meantime, her search for multicellular traits in choanoflagellates has been paying off. In 2003, King and her colleagues reported that long before animals evolved, their ancestors expressed genes coding for proteins involved in three crucial components of multicellular animals: cell adhesion, extracellular matrix, and cell signaling. These proteins were likely necessary for the transition from single-celled organisms to multicellular animals, yet had never been seen in nonanimals.
King and her collaborators also discovered that choanoflagellates contain relatively large numbers of tyrosine kinases, enzymes that form an intracellular signaling system that is critical for coordinating complex processes in animals. Among their many roles, tyrosine kinases in animals regulate cell proliferation, but their functions in choanoflagellates were unknown. When King used chemical inhibitors to block the activity of the enzymes in choanoflagellates, cell division slowed. This revealed functional similarities between these tyrosine kinases and their counterparts in animals.
In King's view, it's most likely that the origin of animal multicellularity occurred when the unicellular ancestors of animals underwent cell division but failed to separate completely. Eventually, some formed stable colonies, and over time cells became differentiated for various functions, leading to the evolution of the first metazoans. The selective advantage of forming colonies isn't entirely clear, but King hypothesizes that it made the organisms more efficient in capturing the microbes that were their major food source.