What is true for human sperm is true for fly sperm

ResearchBlogging.orgWell, sort of. PLoS Genetics published a cool article yesterday titled, “Widespread Presence of Human BOULE Homologs among Animals and Conservation of Their Ancient Reproductive Function” by Chirag Shah, et al. This is cool because a gene involved in sexual reproduction (which normally is a hotbed of selection) is actually conserved – sequentially, expressively and perhaps functionally – among almost all animal phyla. Details below!

Sperm (size, shape, and motility), eggs, gonad structure, testis size, etc. show a remarkable range of diversity. Just read Dr. Tatiana’s Sex Advice to All Creation for a rundown. (Very humorous book, by the way). However, because sexual reproduction is a defining feature of most animals, something must provide a common base from which all of this diversity can arise. Unless you subscibe to the creation theory of life, of course, in which that base isn’t necessary…

Anyway, meiosis is clearly an important feature to consider and is where the most research takes place in this area (according to the authors, anyway), but what about gametogenesis? Is this a conserved feature across the higher taxa or did it evolve multiple times in indepenent lineages? Is there an …Ur…gametogenes…titian? Yeah, Urgametogenestitian… probably doesn’t work but that is definitely a sweet word I just made up!

Alright, back to the subject at hand. Even though genes involved in sexual reproduction are often a site of rampant natural selection and divergence (the Y chromosomes of humans and chimps are a great example which I will be blogging about in the next couple weeks), can there be an underlying mechanism? Are there any common genes? This is what Chirag Shah, et al. wanted to discover.

They first set some limits – what exactly are they looking for in a common gametogenic factor? It first has to be present in most, if not all, sexually reproducing animals. Second, this gene had to have arisen when gametogenesis evolved. Which is kind of a corollary of the first requirement, but whatever. Third, they wanted a gene that was conserved not only sequentially (which isn’t too hard to pull off), but also at the levels of expression and function.

Finally, and perhaps most interestingly, they wanted a gene that was expressed in a specific sex. Why? They worried that a gene that was involved in sexual reproduction may also be involved elsewhere in the body for non-reproductive purposes and was only conserved because it proved too crucial to the body-at-large to be eliminated. To ensure this wasn’t the case, they wanted to be able to knockout a gene and be able to observe a loss of function in one of the sexes. If the gene is male-specific, for example, a knockout would not affect the female because as long as the gene is involved in spermatogenesis, the female should be fine. If the gene is involved elsewhere, the female would be affected, and the authors would know the gene is expressed outside of gametogenesis. Pretty slick, eh?

Shah, et al. settled on Boule as a candidate, a human gene involved in spermatogenesis, that also had studied homologs in Drosophila, C. elegans, and frogs. Oddly, Boule in Drosophila is male-specific, but the C. elegans homolog, daz-1, is female-specific. (This will come up later.) Shah, et al. proceeded anyway.

What they discovered is pretty cool – Boule homologs are found in both deuterostomes and protosomes, which they already knew, but also in Cnidaria! That’s getting fairly close to the evolution of spermatogenesis (Figure 1)! They were unable to find it in the sponge they examined unfortunately, but they note that the sequence they used was only a preliminary draft of Amphimedon queenslandica. No homolog was found in <a href="http://en.wikipedia.org/wiki/Trichoplax&quot;Trichoplax, a sexual metazoan more primitive than the sponges, however. (According to Wiki, fertilization has never been witnessed in this species but it does have cells that resemble sperm.) Boule homologs also aren’t found in plants or fungi. I definitely wonder what the function of Boule‘s ancestor was though.

Figure 1. Phylogenetic distribution of motile sperm, Boule and Dazl homologs among species from major lineages of the animal kingdom and fungi.

They also found that DAZ, a family member of Boule in humans, is only found in vertebrates. DAZ will make an appearance in the Y chromosome series so watch out for it!

Boule is also highly conserved. Shah, et al. examined two protein domains specifically and found that the gene is actually under purifying selection, not the positive selection normally found in sperm-related genes. Purifying selection implies that this gene is important and individuals are less fit without it.

Now that they knew there was a sequential conservation for Boule, Shah, et al. looked at expression levels and found that Boule is primarily expressed in the testes (with C. elegans as a strong exception) but low levels of it can be found in the ovaries of various animals early in development. Expressive conservation confirmed.

Functionally, an experiment on mice produced results to the above scenario: Boule was knocked out in males and they proved to be normal except they were infertile. Mutant females were fine and reproduced successfully. When they examined the testes in more detail, they found that structurually wildtypes and mutants were the same, but when they looked deeper, Shah, et al. discovered that spermatogenesis had been “global[ly] arrest[ed].” Spermatogeneis was stopped at the very beginning! Weirdly, the same thing happened in Drosophila, even though the homology between deuterostomian and protostomian gonads is currently unclear. Ignoring C. elegans, Boule may be functionally conserved across animalian taxa.

C. elegans shouldn’t be ignored though. The authors speculate that a spermatogenic role is ancestral to Boule and it switched to oogenesis in the nematode lineage (Ockham’s razor and all that), but the sample is just too small to be sure. Study of more protostomes is essential to knowing if Boule is actually functionally conserved or not. The authors do speculate that perhaps Boule served a role in gametogenesis generally and subsequently became sex-specific. But what does the Boule homolog in Cnidaria do? Can it be found in Porifera? This paper is definitely an example of a result producing many more questions than what it answers.

It is always cool to find another aspect of ourselves that is common to other animals. The results of the paper aren’t all that surprising – this is something we have come to expect, in fact – but I don’t think we’ll ever tire of it. I mean, we know that the Hox family can be found in most animals, showing that we share the same developmental tools with fruit flies, but genes like Boule show us that even our sperm share something with flies! Isn’t that just awesome to know?

Chirag Shah, Michael J. W. VanGompel, Villian Naeem, Yanmei Chen, Terrance Lee, Nicholas Angeloni, Yin Wang, & Eugene Yujun Xu (2010). Widespread Presence of Human BOULE Homologs among Animals and Conservation of Their Ancient Reproductive Function PLoS Genetics, 6 (7) : 10.1371/journal.pgen.1001022

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