During sperm production, an enormous amount of DNA has to be packed into a very small space without breaking anything. Protamines are the key to this compression, wrapping the DNA thread tightly, but humans have a second type of protamine which had an unknown purpose. Insights into this key mechanism are described in PLoS Genetics.
During the production of human sperm cells, DNA has to be packed into a tiny space, not unlike trying to cram too many clothes into a tiny suitcase to go on holiday. DNA is normally in a comparatively loose tangle. In sperm cells, however, it is enormously compressed. The 23 DNA threads have a total length of one metre and have to be packed into a head just three thousandths of a millimetre in diameter. All of this must happen without the delicate DNA threads tearing or becoming inextricably tangled up.
We often sit on packed suitcases to close them, and the body uses a similar trick during spermatogenesis. “If DNA were to take up as much space as a watermelon under normal circumstances, sperm cells would then only be as big as a tennis ball,” explained Professor Hubert Schorle from the University Hospital Bonn.
This process is termed hypercondensation. In their loose state, DNA threads are wrapped around numerous spherical protein molecules, the histones. In this state, they resemble 23 tiny strings of pearls. During hypercondensation, the histones are first exchanged for transition proteins, which are in turn are replaced by so-called protamines. Due to their chemical composition, protamines exert a very strong attraction on DNA, causing it to wrap itself in very firm and tightly loops around the protamine
“Most mammals seem to produce only one type of protamine, PRM1,” explained Dr Lena Arévalo, a postdoctoral researcher in Schorle’s group. “In humans, but also rodents like mice, it’s different — they have a second type, PRM2.” Until now, it was unclear what this second protamine is needed for. It was however known that some parts of it are successively cut off during sperm development.
These cut-off parts that appear to be immensely important, according to the new study. When mice produce only a truncated PRM2 molecule that lacks the cut-off snippets, they are infertile. “The removal of transition proteins during hypercondensation is impaired,” Dr Arévalo said. “In addition, the condensation seems to proceed too quickly, causing the DNA strands to break.”
It is possible that a defective protamine 2 can also lead to infertility in human males. The team now plans to investigate this hypothesis further, thanks to their lab being the only one so far that has successfully generated and bred PRM and PRM2 deficient mouse lines.
Source: University of Bonn
