Scientists unpick genetics of first 15 minutes of life

Scientists have identified the gene responsible for controlling a first key step in the creation of new life, according to new research published in the journal Nature tomorrow (Thursday 27 October 2005).

The gene, known as HIRA, ‘chaperones’ the early processes that take place once a sperm enters an egg, giving it a crucial role in the most fundamental process in sexually reproducing animals.

The absence or mutation of this gene in the maternal (mother’s) genome explains why eggs fail to produce a zygote – or early embryo – despite the presence of ‘healthy’ sperm.

Although the researchers use the fruit fly Drosophila melanogaster to discover the basic genetic processes of sex, the same genetic processes are present in all sexually reproducing animals, including humans.

“All sexually reproducing animals do the same kind of DNA ‘dance’ when the DNA from the mother’s egg cell and the father’s sperm cell meet for the first time,” said Dr Tim Karr from the University of Bath (UK) who worked closely with Drs Benjamin Loppin and Pierre Couble from Centre de Génétique Moléculaire et Cellulaire (France) on the project.

“When the sperm enters the egg, the DNA it carries needs to be re-packaged so that it can engage in normal cellular activities, including combining with the maternal DNA in the first act of genetic fertilisation.

“A single gene, HIRA, looks after this re-packaging process, making it fundamental for those first 15 minutes in the regeneration of a new life.”

When sperm cells are created, the molecule that the sperm DNA is wrapped around (called chromatin) is remodelled by swapping the type of ‘packing material’, known as histone proteins, it contains.

When it arrives at the egg cell, however, the sperm DNA needs to be re-packaged with a new set of histone proteins so that the sperm DNA can engage in normal cellular activities. The result is called the male pro-nucleus.

To understand how this process occurs, the researchers used a type of mutant fruit fly, known to biologists as a sésame mutant, which they know does not form a proper male pro-nucleus.

By highlighting the chromatin and watching the changes it goes through at different stages of the fertilisation process, the scientists found that the pro-nucleus in sésame mutant is wound into a tight ball that could not interact with its female counterpart, the egg pro-nucleus.

This showed that there was a problem with the re-packaging process in the sésame mutant.

The researchers looked at the genetic makeup of the sésame mutant and identified what is known as a point mutation in the HIRA gene – showing that HIRA is the gene responsible for chaperoning the assembly of the sperm pro-nucleus.

“This is one of the most crucial process that takes place in sexually reproducing animals,” said Dr Karr who works in the Department of Biology and Biochemistry at the University of Bath.

“Sperm DNA has to undergo a complete transformation when it arrives in the egg cell so that it can properly join with the female pronucleus to form a new genetically complete life form.

“A slight mutation in the HIRA gene means that life does not even get started.

“Amazingly we still know relatively little about the structure of sperm DNA and the genetic processes involved in the most crucial early phases of reproduction.”

Because of the particular type of histone protein used in the re-packaging of sperm DNA, the researchers believe that this process leaves its mark in the genome of the newly-formed organism.

This genetic marker could be a useful way of tracking the genetic material an offspring inherits from either their father or mother.

The research was funded by a Wolfson Royal Society Merit Award, the Centre National de la Recherche Scientifique and the French Ministry of Research.