What is C. elegans and why do scientists use it to study human development and disease?

    This question leaps to the minds of most people when they first learn that scientists study a small soil nematode worm to gain insights into human development and disease.  It is a reasonable question with a very straightforward answer:  evolutionary conservation of gene function, as described below.


C. elegans

Photo by Erik Lundquist

  C. elegans is a small soil worm or nematode, and it shares a common ancestor with humans that lived in the pre-Cambrian era, 500-600 million years ago.   This ancestor is referred to as the urbilaterian ancestor, as it is the relative of all bilaterally symmetric, multicellular organisms on the planet, including invertebrates (insects, nematodes, sea urchins) and vertebrates (mammals, fish, birds, reptiles).

    Most of the genes and genetic mechanisms that govern modern organismal development, including those involved in human development and disease, were present in the urbilaterian ancestor and are shared by existing animals, including humans and nematodes.

    Evolution is a process by which existing genetic mechanisms are conserved but changed slightly to result in distinct species.  As the descendants of the urbilaterian ancestor evolved, core pathways governing development were generally conserved but slightly modified in each distinct species by this evolutionary “tinkering”.

    As a result, C. elegans nematodes have neurons, skin, gut, muscles, and other tissues that are very similar in form, function, and genetics to those of humans.  The genes that control the development and function of these tissues have been “conserved” from our common ancestor.  While there are clear and important differences in human and nematode development, scientists can study developmental mechanisms in C. elegans to understand the basic, core mechanisms that also operate in humans.

    This is extremely important, as many developmental and genetic experiments are impossible in humans, and are very time-consuming and expensive in mice and other vertebrates.  C. elegans are easily cultured in the laboratory, have a short (4-day) generation time, and come with a “toolkit” of genetic and molecular techniques by which gene function in development can be experimentally dissected.

    Because of evolutionary conservation of gene function and experimental tractability, C. elegans represents an ideal “model organism” to study basic genetic and molecular mechanisms of human development and disease.  Studies on C. elegans are relevant to human diseases such as cancer, neurodegeneration (e.g. Alzheimer’s disease), neurodevelopmental disabilities and syndromes, muscular dystrophies, and aging, which is not itself a disease but influences the other diseases mentioned.  Indeed, genetic mechanisms important in cancer (Ras and Bcl oncogene signaling), aging (insulin signaling), and nervous system development (UNC-6/Netrin signaling) were first identified using C. elegans.

C. elegans with green fluorescent protein (gfp) expression in neurons.