Our DNA is tightly packed in the nucleus. Each chromosome is one long DNA molecule wrapped around a protein called a histone, like a very tiny thread on a very tiny spools.
But sperm even puts the packing skills of chromosomes to shame.
“If DNA took up as much space as a watermelon under normal circumstances, then sperm would be the size of a tennis ball,” said Hubert Schorle, a researcher at University Hospital Bonn.
In humans & in mice, 2 proteins called protamine re-place histones to pack DNA even more densely, using each space like the blocks in a game of Tetris. This process is called hyper condensation.
How this happens is pretty well understood, but Schorle and a team of researchers have dug deeper into the hypercondensation process and looked at what happens when you mess with one of these protamines, PRM2.
During the entire process of creating sperm, a part of the PRM2 protein called N-terminus is cut-off. This cutting-off, or cleaving, seems to be necessary to make sperm, well sperm.
“Proper cleavage of PRM2 therefore appears to be crucial for successful reproduction yet, however, the function of the cleaved PRM2 domain & PRM2 processing remain unknown to date,” the team writes in their paper.
To find out what was going on, the researchers created mutant mice that didn’t have an N-terminus on their PRM2 to delete. After examining their sperm closely, the team determined that PRM2 definitely needs to be cut-down to size, since mice with uncleaved PRM2 had DNA that completely fell apart.
First author Lena Arévalo, also from the University Hospital Bonn, said: “The removal of transition proteins during hyper condition is impaired.
“Also, the condensation seems to happen so quickly that the DNA strands to break.”
This, unsurprisingly, resulted in infertile males, but only if both copies (or alleles) of PRM2 were lost or damaged. When only one of these genes was lost, the mice remained fertile. You can see diagram of this below.
While we do not yet have direct evidence of this action in humans, it is possible that problems with human fertility could sometimes caused by issues with PRM2 cleaving. The team is currently investigating whether this is the case.
“Only a few research groups have analyzed the role of protamine in hyper condensation,” says Schorle.
“We are so far the only laboratory in the world that has succeeded in generation & reproducing PRM1- and PRM2-deficient mouse lines, which are now being used to study the role of these proteins in spermatogenesis.