Dr Spillane's Genetics & Biotechnology Lab in the Dept of Biochemistry & Biosciences Institute at University College Cork (UCC) is working on SFI-funded research to improve scientific understanding of why some genes on plant and mammalian chromosomes are only active when inherited from either the mother or the father. The ground-breaking research was conducted as part of an ongoing international collaboration between Dr Spillane's research group, and the groups of Professor Ueli Grossniklaus (University of Zurich) and Dr Karl Schmid (Max Planck Institute of Chemical Ecology, Germany).

Genes with memory!

We inherit two copies of every gene from our parents, one from our mother and one from our father. For the majority of the 30,000 or so genes on our chromosomes that we inherit from both parents, both copies are active. However, it emerged in the 1980s that for a small number of genes, the only active copy is the one inherited from our mother. An approximately equal number of other genes behave in the opposite manner, where only the copy inherited from your father is active. To date, almost 100 such genes have been identified that behave in this unusual manner. Such "imprinted" genes can flip between being on (working) and off over successive generations, simply depending on whether the gene copy is passed on by a mother or a father to the offspring.

No new mutations in the DNA are responsible for the change in the on/off activity of such imprinted genes. This is because the genes were epigenetically "imprinted" when they were in the egg or sperm, which allows them to remember whether they were inherited from the mother or the father. "Epigenetics" is a term used to describe an exciting new frontier of genetics where scientists such as Dr. Spillane are studying heritable changes in gene function that occur without a change in DNA sequence. According to Dr. Spillane, "there are now far-reaching implications of epigenetic research for agriculture, and for human biology and disease, including our understanding of cancer, nutrition, stem cells, and ageing. The fundamental research that is now being done in this area is paving the way for future applications in agriculture and medicine".

Epigenetically regulated imprinted genes are emerging as key genes controlling human susceptibilities for asthma, cancer, diabetes, obesity, and many behavioral and developmental disorders. To date, imprinting disorders have been linked to Alzheimer's disease, autism, bipolar disorder, diabetes, male sexual orientation, obesity, and schizophrenia; as well as an increasing number of cancers.

Battle of the sexes

Genomic imprinting has only been found in placental mammals (such as humans) and flowering plants. Little is known about how imprinting arose during the evolution of mammals and plants. One major theory is the parental conflict theory which proposes that imprinting of some genes occurred because of a battle or conflict between the sexes to control the maternal allocation of resources to their offspring. This theory proposes that paternally active imprinted genes can enhance the extraction of nutrients from the mother during pregnancy, whereas maternally active imprinted genes seek to limit such nutrient extraction. Where such genes have opposing (or antagonostic) effects there is potential for an evolutionary "arms race" to arise between the proteins coded for by each gene. Such genetic battles between the mother's and father's genes played out in the embryo can affect health and behaviour throughout our lives.  

Genomic imprinting and sexual conflict in plant seeds

While a human embryo is nurtured by the placenta, the embryo of a seed plant is nourished by a nutrient-rich storage tissue called the endosperm. So why is plant endosperm of scientific interest? The starchy endosperm of seeds is the basis of our planet's food supply, as it is the nutritive part of cereals and the key component of all seeds that we depend on for carbohydrates, protein and oils. Crop seeds such as rice, wheat and maize provide over three quarters of the world's food energy intake. Dr Spillane stresses that "By understanding the genetics of how endosperm is made will help us to breed and develop better crops for the future, whether for food, bioenergy or biomaterials purposes. This has important implications for future food and energy supplies".

Dr. Spillane and his collaborators studied a maternally active imprinted gene in plants called MEDEA.  Without the MEDEA gene the endosperm of the seeds aborts, and the aborted seeds have giant embryos, suggesting that MEDEA controls the allocation of resources to the embryo. They discovered that the MEDEA gene arose sometime in the past 35-85 million years as a result of a duplication of the entire set of genes in an ancestor of the plant species Arabidopsis thaliana. This meant that the Arabidopsis genome also harbored a duplicate gene copy of MEDEA which was called SWINGER.

What was surprising was that while both of these genes were active in the same locations in the seed, only the MEDEA gene was active in the nutritive cells and tissues giving rise to the endosperm. They found that while the MEDEA gene was imprinted and essential for making seeds, the duplicate SWINGER gene was neither imprinted nor essential for seed development.

To investigate how these two duplicate genes could have evolved different functions, the researchers analysed the gene sequences and found that the amino-acid sequence of the MEDEA gene was very rapidly changing, compared to the slower rate of change for the SWINGER gene. This was a very exciting finding as it indicated that the imprinted MEDEA gene was undergoing a form of "evolutionary race" likely driven by a genetic "conflict" between the maternal and paternal genomes over allocation of resources to the embryo in the developing seed. In this regard, the study provided the first strong evidence based on rates of protein evolution supporting the parental conflict theory for the evolution of imprinted genes.

Science Foundation Ireland

Dr. Spillane's research group are funded by Science Foundation Ireland (SFI). SFI was established in 2003 to invest in academic researchers and research teams who are most likely to generate new knowledge, leading edge technologies and competitive enterprises in Ireland. Prior to returning to Ireland in 2003, Dr Spillane was researching genomic imprinting in Switzerland, and also at the Cold Spring Harbor Laboratory in New York. Based on research experience gained in the UK, Italy, Switzerland and the USA, Dr. Spillane highlights that "If Ireland is to strive over the next decade to become internationally competitive in science, technology and innovation there is a need for greater and sustained investment in both fundamental and applied research".

Weblinks

Dr Spillane's lab website: http://www.ucc.ie/spillane

Genomic imprinting website: http://www.geneimprint.com

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