Biological meaning

At ComBio, Maleszka will argue that while large-scale genomic projects are here to stay, single gene and single network analysis is largely heading for obsolescence. He believes that with so many genomes being sequenced, technology developing so fast and mountains of information so available, biologists are in danger of drowning in data.

“We have to begin to convert that massive amount of raw data into real biological meaning,” he says. “For many years people have been studying biology gene by gene, taking various genes and trying to connect them to various phenotypes and behaviours, but I think that is no longer an interesting approach. It is not going to generate the understanding of how such complex biological systems work.

“The work on the bees is a good example of where you are getting information from the genome and you identify individual genes, but now there is a global genome-wide control of development, through methylation and epigenetics for example, so what I will argue is that we not only have to try to bridge this gap from genotype to phenotype, but we also have to bridge the gap between genotype and environment. In many cases you can see evidence that the genome is being modulated by the environment and epigenetic controls are responsive. I think we need to look into those massive amounts of data and look at systems biology more than individual genes.

“The genomic is useful of course but looking at those genomes for the sake of sequencing them is not necessarily helpful. Reshuffling and channelling our resources into addressing specific questions and looking at global genetic and epigenetic systems and how environment modulates and controls it, that is helpful. We have problems now with obesity and diabetes and clearly they are environmental. That is why insects, and especially the honey bee in this case, are very useful as a model to identify some of those mechanistic switches that also exist in humans.”

Royals and Anarchists

Royal jelly makes the queen, and the so-called Major Royal Jelly Proteins (MRJPs) are probably responsible. Maleszka’s research has shown that MRJPs are encoded by a set of nine genes found in the same region as the yellow family, which play a diverse role in pigmentation, development and sexual maturation in insects. Yellow genes are found only in insects and bacteria, and it is thought they came from symbiotic bacteria by horizontal transfer.

Maleszka’s team has also shown that royal jelly proteins retain some of the ancestral roles associated with the yellow proteins and may serve as developmental regulators or activators of biochemical pathways.

In queen bee development, the selected larva receives an enormous amount of royal jelly, which is sensed by the gut epithelium and is metabolised by the fat body, the insect version of a liver. This then activates the insulin pathway, which then activates the juvenile hormone that controls many metabolic sub-networks in bees. This leads to a rapid demand for more nutrients and then the astonishingly rapid growth of the young queen.

In addition to looking at honey bee epigenetics and proteins, Maleszka and his team have been studying honey bee genes involved in learning and behavioural development. A decade ago, ANU put up some money to create a project in which the molecular and the behavioural levels were studied side by side. “The idea was to try to combine the power of genetics and molecular biology with the well-established behavioural studies on the honey bee at ANU and see if we can bridge those two levels of biological complexity and get a new idea of how behaviour is generated from the genome,” he says.

“The idea was to understand some of the genes involved in learning and memory but also those genes that generate social behaviour. The main attraction of the honey bee is that it is a social organism, so there is this extra level of biological complexity in comparison to the famous vinegar fly, Drosophila. Everyone was very anxious to understand how very similar genomes can generate such different outputs in social and solitary species.”

Another very interesting project his team is involved in is helping Professor Ben Oldroyd from the University of Sydney with technical aspects of his work on the mechanisms of social cohesion in bee colonies. Oldroyd has created a strain of “anarchistic” bees in which workers are able to lay eggs, and lots of them.

The anarchist bees will be useful for investigating how worker sterility is maintained in normal colonies, and to isolate and characterise the genes that control worker sterility in social insects. These genes may prove to be the semi-mythical genes for altruism, Oldroyd says.