One of the biggest competitions out there is the battle between sperm cells racing to make it to the egg first. Considering the millions of sperm cells that compete, and the fact that on most occasions there is only one winner, the race is bound to be intense – and get a little ruthless sometimes.
A key part of this competition is motility, as sperm that can move better have a higher chance of getting to the egg first to fertilize it. Now, researchers from the Max Planck Institute for Molecular Genetics have shown, using mice, that an active protein called RAC1 is really important for the ability of sperm to move progressively. Sperm that have the optimal amount of this protein have a better chance to compete, and those that don't fail miserably.
The interesting part of the new study, published in PLoS Genetics, is that mice contain a "selfish" gene fragment that breaks the standard rule of genetic inheritance, providing some sperm cells with a 99% success rate if they have it. The researchers described the genetic segment as a “t-haplotype” (t-sperm) which contains gene variants. They have shown for the first time that the mice sperm that contain it have more progressive movement abilities and can move faster forward compared to their peers, which increases their chances of fertilizing the egg.
Furthermore, the researchers linked this "selfish" genetic segment to the active RAC1 protein. This protein acts as a switch, relaying information from the outside to the inside of cells by activating other signaling molecules. It is known to have functions in directing cells such as immune cells to their targets. The authors of the new study hypothesized that RAC1 might also be helping sperm cells to "sniff" their way to the egg.
“The competitiveness of individual sperm seems to depend on an optimal level of active RAC1; both reduced or excessive RAC1 activity interferes with effective forward movement,” said Dr Alexandra Amaral, first author of the study, in a statement.
More interestingly, the authors found that t-sperm cells that contained the t-haplotype genetic segment could disable other sperm in the competition that did not contain it. Early during spermatogenesis (the maturation of sperm), certain distorting factors are distributed to all t-sperm cells specifically. These factors are in a sense the poison, and could distort regulatory signals in other "normal" sperm, diminishing their movement abilities.
“Sperm with the t-haplotype manage to disable sperm without it,” said Bernhard Herrmann, Director at the MPIMG and of the Institute of Medical Genetics at Charité – Universitätsmedizin Berlin, and corresponding author of the study. “The trick is that the t‑haplotype “poisons” all sperm, but at the same time produces an antidote, which acts only in t-sperm and protects them,” he explained. “Imagine a marathon, in which all participants get poisoned drinking water, but some runners also take an antidote.”
During sperm formation, chromosomes are evenly split, and each sperm receives half of the original copies in the precursor cell that divided. Only the t-haplotype sperm that inherit a copy of the chromosome containing this genetic segment produce an additional factor that can reverse the negative effects of the distorting factors from other t-sperm. Therefore they are not influenced and are in a sense protected compared to sperm that do not have it.
The study did point out that t-sperm have no advantage if they are left on their own, without normal sperm to compete with.
For example, when the researchers tested male mice with the segment on only one of the two copies of chromosome 17 (the chromosome where the t-haplotype segment is inherited from) they had a mixture of t-sperm and "normal" sperm. They noticed that it was mostly the normal sperm that had difficulties in moving forward, illustrating the competitiveness of the t-sperm in outperforming them due to their dirty trick of poisoning with distorting factors, which made the normal sperm move slower.
However, when they applied a substance to the second group of mixed t-sperm and normal sperm that inhibits the ability of the active RAC1 protein, they observed that the normal sperm were also able to swim progressively. This took the advantage of t-sperm away, as abnormal RAC1 activity disturbs progressive motility.
The researchers then concluded the reason why some male mice that inherit two copies of the genetic segment on both their copies of chromosome 17 are sterile. This is because during spermatogenesis these mice only produce t-sperms, which contain too much RAC1 and don't have any normal sperm to compete with. This in turn results in their own motility diminishing, and the t-sperm almost cannot move forward. Thus, the authors pointed out, too little RAC1 protein can reduce motility, too much of it can do the same, and hence some forms of male infertility in humans might be a result of aberrant RAC1 activity. However, further research in the future is needed to investigate that.
"Our data highlight the fact that sperm cells are ruthless competitors," stated Herrmann. Furthermore, the example of the t-haplotype demonstrates how some genes use somewhat dirty tricks to get passed on. "Genetic differences can give individual sperm an advantage in the race for life, thus promoting the transmission of particular gene variants to the next generation," he concluded.
