Harmit Singh Malik: Why Are Protamines Essential for Male Fertility?
Harmit Singh Malik, Investigator at Howard Hughes Medical Institute and Affiliate Professor at The University of Washington, shared a post on LinkedIn about 2 articles he co-authored with colleagues:
“Most animal species pack sperm DNA with protamines instead of histones.
Protamines are essential for male fertility.
They are among the fastest-evolving genes in animals.
That makes little sense.
We think we know why, in a new paper led by former postdoc Ching-Ho Chang (who is now an Assistant professor at the Institute for Molecular Biology in Academia Sinica, Taipei, Taiwan):
We took a fly protamine, Mst77F, which is both essential for male fertility in D. melanogaster and among the fastest-evolving genes, and swapped in versions from related species.
We also halved its dose. In both cases, sperm carrying the X chromosome compacted their DNA more slowly.
As a result, those X-bearing sperm dropped out during spermatogenesis. Males fathered more than 60% sons (sometimes 70%) instead of 50%. Mendel’s fair coin is rigged.
Ching-Ho Chang actually predicted this very outcome in a previous paper.
That is meiotic drive. Something (we think Y-linked) kills sperm that carry a target on the X. Mst77F protects them.
Crosses of fused sex chromosomes (attached X^X and attached X^Y) confirm this.
We do not know the target yet, but we ruled out the obvious suspect: a giant satellite repeat on the X.
What about other Drosophila species? We deleted Mst77F in D. yakuba, but surprisingly, it did not cause sterility. However, it still skewed the sex ratio. Thus, policing drive may be the older job for Mst77F, with fertility as the recent add-on.
TL:DR; male fertility essential protamines still evolve fast because they are in an arms race with selfish genes on the sex chromosomes.
Although Mendelian inheritance is ubiquitous, it is a fragile truce, and itself is a Red Queen conflict: ‘running hard to keep in place’.
The lion’s share of the credit for this project goes to Ching-Ho Chang for conceiving it, and to a number of older and newer co-authors who helped finish all the crosses, as he and some of the fly stocks crossed (and were lost over) the Pacific.
If you are keen on this work, check out the ECG Lab.
Ching-Ho has some very clever projects cooking and would be interested in hearing from prospective techs, grad students, and postdocs.”
Title: Rapid protamine evolution suppresses meiotic drive in Drosophila.
Authors: Ching-Ho Chang, Aida Flor A. de la Cruz, Hung-Yu Lai, Isabel Mejia Natividad, Alex Noyola, Elian Angelo, Magsino Abellanosa, Harmit S. Malik.
You can read the Full Article in Science Advances.
Title: Expansion and loss of sperm nuclear basic protein genes in Drosophila correspond with genetic conflicts between sex chromosomes.
Authors: Ching-Ho Chang, Isabel Mejia Natividad, Harmit S. Malik.
You can read the Full Article in eLife.
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