make GO:0060468 | prevention of polyspermy more general

[ValWood]

To describe the fertilization block in Nature. 2018 Aug;560(7718):397-400. Epub 2018 Aug 8. Gamete fusion triggers bipartite transcription factor assembly to block re-fertilization.

the authors selected the GO term: GO:0060468 | prevention of polyspermy

I wonder if we could generalise this term The negative regulation of fertilization process that takes place as part of egg activation, ensuring that only a single sperm fertilizes the egg.

i.e term name: negative regulation of re-fertilization?

The negative regulation of fertilization process after initial fertilization event that prevents the fusion of more than two gametes? Or something along those lines?

[ValWood]

The parent of GO:0060468 | prevention of polyspermy GO:0007343 egg activation The process in which the egg becomes metabolically active, initiates protein and DNA synthesis and undergoes structural changes to its cortex and/or cytoplasm. looks incorrect.

Presumably these are parallel processes. GO:0060468 | prevention of polyspermy can be independent of egg activation (although they occur simultaneously?)

[ValWood]

GO:0007343 egg activation part_of single fertilization looks like a possible TPV?

[ukemi]

This doesn't sit well with me, but assigning to @vanaukenk to get another developmental biologist's opinion.

[ValWood]

In this case maybe a general parent term?

[ValWood]

GO:0009566 fertilization Definition The union of gametes of opposite during the process of sexual reproduction to form a zygote. It involves the fusion of the gametic nuclei (karyogamy) and cytoplasm (plasmogamy).

The union of gametes of opposite sexes or mating types during the process of sexual reproduction to form a zygote. It involves the fusion of the gametic nuclei (karyogamy) and cytoplasm (cytogamy).

plasmogamy does not even exist in GO, should it be added as an exact synonym of cytogamy?

[ValWood]

https://en.wikipedia.org/wiki/Plasmogamy narrow symonym ?

[ValWood]

To support "Presumably these are parallel processes. GO:0060468 | prevention of polyspermy can be independent of egg activation (although they occur simultaneously?)" above

In conclusion Thus, mating repression in zygotes shares components with, but bifurcates from, meiotic induction.

[ValWood]

nice summary placing into context with other fertilization blocks:

"Mechanisms preventing re-fertilization ensure ploidy maintenance across generations in evolutionarily divergent phyla. These mechanisms generally involve rapid changes, such as the release of cortical granules and shedding of surface receptors in mammals1, membrane depolarization in amphibians 4,25 and the degradation of pollen guidance cues in plants . Our results provide a first glimpse into fungal re-fertilization blocks, by showing that yeast zygotes rapidly initiate transcription to discontinue mating. Whereas Mi peptides are fast-evolving peptides that we could only identify in the Schizosaccharomyces lineage by genome position, Pi-like homeodomain proteins are ancestral eukar- yotic proteins that are extensively used in developmental processes27. Their primordial role may be in the haploid-to-diploid transition28, which suggests that their rapid post-fusion activation is used elsewhere to block re-fertilization. For instance, rapid post-fusion homeodomain complex formation and nuclear translocation has previously been observed in Chlamydomonas reinhardtii 29."

[ValWood]

this is interesting too:

The bipartite design of the Mi–Pi transcription factor—which is reminiscent of hormone nuclear receptors and their ligands30—favours post-fusion activation speed, limited only by the rate at which Mi reaches the nuclear-localized homeodomain Pi protein. Because this simple two-component system inherently leads to asymmetric zygotic expression, asymmetry may follow from the selective pressure to rapidly block re-fertilization. As even a transient cytoplasmic connection is sufficient for formation of an active complex, such transcription factor design may also be used to impart cell fate changes upon—or build sensors to monitor—other instances of transient cytoplasmic bridge formation.

[ValWood]

Final note:

The author also suggested

"Regulation of asymmetric gene expression from parental genomes" Factor that regulates differential gene expression of homologous parental gene copies

Although important, this seems more like a consequence of the mechanism of the fertilization block. I wasn't sure if it was possible to capture this in GO, although there are a few terms related to the generation of asymmetry in development I could not find anything related to asymmetric zygotic expression, or even a general asymmetric process term. Any ideas?

[vanaukenk]

@ValWood - Working on this ticket, I am looking at the term GO:0000747 conjugation with cellular fusion that is a sibling of fertilization. A few thoughts/questions that I have:
If we update the definition of fertilization to include a reference to mating types do these two terms then start to overlap in meaning? Would fertilization then need to be a parent of GO:0000747? How often does the fungal community refer to 'fertilization' vs 'conjugation'?
Would the existing 'negative regulation of conjugation with cellular fusion' be a better term, or parent for a new term, for what you're trying to capture with this paper?

[ValWood]

Thought:

I don't think "fertilization" and "conjugation with cellular fusion" are equivalent.

"conjugation with cellular fusion" is the yeast term for "mating". In fact, nobody really calls this "conjugation with cellular fusion" but we needed to use this term to disambiguate from

GO:0007618 mating The pairwise union of individuals for the purpose of sexual reproduction, ultimately resulting in the formation of zygotes.

which was bagged for the multicellular equivalent.

So i'm not an expert in this at all but I would say that both processes (conjugation and mating) are broader, and result in, or involve the 'fertilization of a gamete'.

It seems that the "prevention of polyspermy" is therefore a post-mating process? (its a bit analogous to the prevention of re-replication after replication has taken place)

I agree, that this would also be a type of "negative regulation of conjugation with cellular fusion", but this is a very general process which could apply at any stage in conjugation and missed the important post-conjugation aspect, very cooly demonstrated by this work (including the exact mechanism).

The solution here would be to have a sibling term to GO:0060468 | prevention of polyspermy

NTR prevention of polyzygosity in spores this could have parentage to a fertilization block, AND "negative regulation of conjugation with cellular fusion"

@mah11 does that sound sensible to you and @Antonialock (I know you are busy too busy to look in detail)

[ValWood]

@mah11 @Antonialock what do you think about this?

is my thinking above correct?

[Antonialock]

I'm not completely following but I agree that conjugation with cellular fusion is analogous to mating.

I am not sure if prevention of polyspermy is always downstream of mating, there must also be mechanims that go on during mating to ensure there is only one cell:cell fusion site?

[ValWood]

so the main question is

"is mating/conjugation" broader then fertilization. I think it definitely is? (nobody uses these interchangably in yeast). Fertilization is only part_of the mating process.

if so, my preferred solution is

make a more general parent "term name: negative regulation of re-fertilization?

The negative regulation of fertilization process after initial fertilization event that prevents the fusion of more than two gametes? Or something along those lines?

make "prevention of polyspermy" a child of this

add a new child:

NTR prevention of polyzygosity in spores this could have additional parentage to "negative regulation of conjugation with cellular fusion"

It would be great if I could do this soon, since it was a high profile Nature paper, and a community curation session. I forgot about it and I'd like to make it live very soon.

[mah11]

prevention of polyzygosity in spores

I agree that adding a new term is preferable to altering the existing GO:0060468, but this phrase does not make sense.

Zygosity isn't the same thing as ploidy, and the emphasis on spore ploidy will make hard to tell that the term would (or should) be usable for any yeasts, and maybe any fungi. (Remember that budding yeast doesn't usually undergo sporulation immediately after conjugation.)

I think it would be better for the term name to describe the actual regulation event itself, rather than its downstream consequences. Ideas:

negative regulation of conjugation with zygote negative regulation of cell fusion with zygote during conjugation negative regulation of conjugation between three or more cells

"is mating/conjugation" broader then fertilization.

I've rarely seen "fertilization" used to refer to anything in yeast, and in the few cases I have seen have been a bit woolly - wordings have been imprecise enough to allow for either the "conjugation with cellular fusion" meaning or just the cell fusion part. So I don't think we should have a fungal-oriented term with "fertilization" in the name; related synonyms would be fine.

I don't know enough to comment on whether all prevention of polyspermy-or-analogous-problem is post-mating, for fungal or broader senses of "mating".

[ValWood]

Thanks!

I like "negative regulation of conjugation between three or more cells" since it is very clear what is being negatively regulated, and why it would be a ~synonym~ sibling? of GO:0060468 | prevention of polyspermy

[ValWood]

Any thought on this. I just noticed that we are still using "prevention of polyspermy" which is incorrect and looks strange!

[Antonialock]

I think I like "negative regulation of conjugation with zygote" best

I think it is more specific than ""negative regulation of conjugation between three or more cells" - this term could also any gene product that ensures that the cell only projects towards one other cell? (maybe?)

I think the "negative regulation of conjugation with zygote" captures the post fusion part ("post-fusion reconstitution of a bipartite transcription factor blocks re-fertilization")

I also think that the paper uses some "unconventional yeast language" - probably to put it in context of the broader scientific audience. I don't think yeast researchers typically refer to vegetatative or shmooing cells as 'gametes'. Or 'fertilization'.

[ValWood]

OK let's go with that. We can always improve later.

I also think that the paper uses some "unconventional yeast language" - probably to put it in context of the broader scientific audience. I don't think yeast researchers typically refer to vegetatative or shmooing cells as 'gametes'. Or 'fertilization'.

That may be so but GO is supposed to normalize different language, or at least identify common parents.

[ValWood]

@vanaukenk there seems to be a solution agreed on but not implemented. Cheers Val

[ValWood]

I think the proposal was NTR "negative regulation of conjugation with zygote" (although we do not have "conjugation with zygote")

Can anyone suggest an appropriate definition?

[Antonialock]

"A process that prevents a zygote from fusing with additional cells " ?

[ValWood]

"A process that prevents a zygote from fusing with additional gametes " ?

[Antonialock]

maybe it is personal but I dislike calling yeast cells gametes

[ValWood]

OK! A process that prevents a zygote from fusing with additional cells "

[pgaudet]

So, the action is

NTR "negative regulation of conjugation with zygote" A process that prevents a zygote from fusing with additional cells "

• Can you please provide a reference ?
• Are there other actions that I missed ?

[ValWood]

Nature . 2018 Aug;560(7718):397-400. doi: 10.1038/s41586-018-0407-5. Epub 2018 Aug 8. Gamete fusion triggers bipartite transcription factor assembly to block re-fertilization Aleksandar Vještica 1, Laura Merlini 1, Pedro Junior Nkosi 1, Sophie G Martin 2 PMID: 30089908

[pgaudet]

1. Added new term:

+[Term] +id: GO:0140538 +name: negative regulation of conjugation with zygote +namespace: biological_process +def: "A process that prevents a zygote from fusing with additional cells." [PMID:30089908] +is_a: GO:0060467 ! negative regulation of fertilization +property_value: term_tracker_item https://github.com/geneontology/go-ontology/issues/16329 xsd:anyURI +created_by: pg +creation_date: 2020-11-07T07:50:23Z

2. Made 'GO:0060468 prevention of polyspermy' a child of that new term.

Thanks, Pascale

[ValWood]

@Antonialock

Aleksander requested

There are two findings in the paper that I failed to capture by the availble terms.

1) Pi and Mi proteins govern ASYMMETRICALLY zygotic expression of their target mei3, such that it is more rapidly and robustly expressed from the P-cell genome.

2) Pi, Mi, Mei3, and Mei2 function to establish a re-fertilization block in zygotes. In the provided list of terms I have used the term "polyspermy block" which might not be the most suitable given that in yeast zygotes are produced by isogametes.

this term is for 2). Should I just replace the current 'part_of' here?

https://curation.pombase.org/pombe/curs/46c89f342f117ca5/ro

[ValWood]

@Antonialock Ignore, it is further down the session. I worked on this one, I thought it was one of yours.

but why does "prevention of polyspermy" show up as an unknown term? I can still see it in QuickGO, and that should still exist @pgaudet ?

[ValWood]

@pgaudet Any idea what is happening here?

GO:0140538 is not yet available (they usually arrive the next day), and the term we were using GO:0060468 prevention of polyspermy is no longer available (I can't see why, there are no taxon constraints?) but I cant put the session back into our database

[pgaudet]

GO:0060468 prevention of polyspermy has taxon constraints:

GO:0007338 | single fertilization | Never in Taxon | 58024 | Spermatophyta |   GO:0007338 | single fertilization | Only in Taxon | 2759 | Eukaryota https://www.ebi.ac.uk/QuickGO/term/GO:0060468

I dont think this should block it for you ?

===

For GO:0140538 negative regulation of conjugation with zygote: I created it on Nov 7th, and the last snapshot ran on Nov8th, I suppose it just missed it. You can view the most recent snapshot date here: http://snapshot.geneontology.org/metadata/release-date.json

Thanks, Pascale

[ValWood]

no don't worry. I just wante dto check that there wasn't a problem.

vsal

[pgaudet]

the fact that you dont see GO:0060468 seems odd.

[ValWood]

Hmm @mah11 @kimrutherford any ideas (might be a Canto issue)

[ValWood]

I still don't see this term?

[balhoff]

@ValWood I thought we determined in #20362 that this was expected.

[ValWood]

sorry I should be precise ! "this" here is

+[Term] +id: GO:0140538 +name: negative regulation of conjugation with zygote +namespace: biological_process +def: "A process that prevents a zygote from fusing with additional cells." [PMID:30089908] +is_a: GO:0060467 ! negative regulation of fertilization +property_value: term_tracker_item #16329 xsd:anyURI +created_by: pg +creation_date: 2020-11-07T07:50:23Z

the replacement term further back in the ticket.

[balhoff]

@ValWood that term will be excluded by owltools --make-species-subset for the same reasons.

[ValWood]

That term was added for fission yeast though @pgaudet?

[ValWood]

I think we need to put the new term

+id: GO:0140538 +name: negative regulation of conjugation with zygote

directly under sexual reproduction

[balhoff]

directly under sexual reproduction

Looks like that would work.

[Antonialock]

"A process that prevents a zygote from fusing with additional gametes " ?

I realized why I dislike the word 'gamete' for yeasts - and in your proposed context I think it would be ok to call them gamete (but keeping it at cells is also ok! I don't mean that it needs to change, I just wanted to clarify since I just had this epiphany)

Often, papers will refer to "spores" as "gametes" - but I think this is completely incorrect (spores are the progeny! Spores may go on to develop into gametes, but the 'spore form' itself is not a sexually capable state)

[ValWood]

Hi,

I still can't use this term. Is there any issue to moving it directly under 'sexual reproduction' ?

Thanks Vl

[pgaudet]

Hi @ValWood

Do you want 'negative regulation of conjugation with zygote' part_of 'sexual reproduction' ? (I dont think is can be is_a?)

What would be the is_a - the most general in 'biological regulation' but that seems too general.

Thanks, Pascale

[pgaudet]

Or can I use is_a 'negative regulation of reproductive process' ?

[Antonialock]

I don't think 'negative regulation of reproductive process' fits

• it's a QC mechanism to prevent an upstream process from happening again

2 gametes fuse -> zygote formation once the zygote has formed you don't want any other gametes fusing with your zygote.

[pgaudet]

ok - what is the is_a parent then ?

[Antonialock]

I think the current parentage looks ok? ia_a neg reg of fertilization which is part_of sexual reproduction?