Life models Understand article

Model organisms – yeast, worms, flies and mice – help researchers to probe the secrets of life.

When we think of a model, we usually think of something smaller and simpler than the original – like a scale-model railway or a pocket-sized version of a classic car. But models are not always toys: maps are models that encode the details of a landscape, and architects and engineers build models to test their ideas before putting them into full-scale practice.

For decades, molecular biologists have used models in a similar way – studying simpler organisms in place of more complex species, including humans. Such ‘model organisms’ often seem to be quite unlike the species they are used to model. For example, Caenorhabditis elegans (usually known as C. elegans) is a worm that is only a millimetre long, and its lifestyle and appearance are of course nothing like those of humans – yet on a molecular scale it shares with us many fundamental processes of life. Studying C. elegans has led to many important findings that apply not only to that species, but to many others. For example, researchers used C. elegans to study the effects of beta-amyloid peptides, the molecules that build up in the brains of Alzheimer’s patients. This has helped to reveal some of the molecular mechanisms that underlie this disease.

Different, but similar

What is the underlying reason for such similarity across species? Comparing the genomes of many different species has revealed that the genes for many key biological functions have been conserved throughout evolution and are now found across species ranging from bacteria to mammals. So, although worms and humans diverged from a common ancestor millions of years ago, some 40%of the coding genes in the C. elegans genome have human counterparts.

The yeast Saccharomyces cerevisiae, a unicellular organism, is perhaps even more remote from humans – yet this model organism has been vitally important for cancer research. This is because the cell cycle – the set of processes through which cells grow and divide – is so fundamental to life that it has been preserved across all eukaryotic species, including yeast. The cell cycle is also crucial to how cancer cells replicate, so studying this cycle in yeast has led not only to increasing our understanding of a basic life process, but also to clinical benefits.

What makes a good model organism?

Although every model organism has its own advantages, there are some features and advantages that most model organisms share. One of these is small size, as laboratory space is a limited resource. C. elegans scores highly here, as some 10 000 individuals can be kept in a single dish of 10 cm diameter. But perhaps the most important feature shared by all model organisms used in molecular biology, from the bacterium Escherichia coli to the laboratory mouse Mus musculus, is a very short generation time compared to humans. C. elegans, for example, grows from embryo to adult in just three days and has a lifespan of just two to three weeks. This means that experiments involving several generations can be carried out in weeks instead of years.

Using a simpler organism as a model is often an advantage in itself, as it generally makes experiments simpler. For example, the fruit fly Drosophila melanogaster has only four pairs of chromosomes while humans have 23, so Drosophila became a favourite model organism early on for studying how genes are transmitted across generations. It is also a favourite for research linking genetics to behaviour, as it shares with humans and other mammals some important behavioural genes. For example, researchers use Drosophila to investigate the circadian rhythm – the complex biological mechanism that tells us (and flies) when to wake up or sleep. There are fewer factors that influence sleep / wake behaviour in Drosophila than in humans, so it provides a useful simplified model.

Genetic similarity can be another important advantage. The genome of the mouse Mus musculus is similar in size to the human genome, and almost every human gene has a mouse counterpart – which is one reason why this species is so widely used as a model, particularly for human diseases. But sometimes, dissimilarity can also be an advantage: researchers used C. elegans to investigate a human kidney disease with a known genetic cause – even though this species has no kidneys. This meant the organism could stay healthy with the faulty disease-causing gene inserted into its genome, allowing the biochemical pathway that inflicts the damage in humans to be worked out.

Ultimately, the choice of one model organism over another is based on the particular question that researchers wish to investigate. The completely transparent body of C. elegans, for example, is another advantage in developmental biology research: we can observe how every single cell develops in a few days from the fertilised egg, using a simple microscope.

Gene technology and the future

Today, continuing improvements in gene editing techniques, combined with information from fully sequenced genomes, are making it increasingly easy to modify the genetic information within living organisms very precisely. Human genes can now be inserted into other organisms that are genetically or anatomically quite different, thus reducing the need to work with species whose genomes are very similar in nature to our own. In addition, bioinformatics – the application of data processing techniques to biology – can now tell us exactly which genes are shared between humans and model organisms.

Together, these technologies provide limitless scope for exploring the causal links between genes and human disease in simple model organisms. Alongside these potential medical benefits, researchers are also exploring new frontiers of knowledge in the science of life, and the common biological systems that connect all living beings.

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