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Chloe Girard, PhD @chloegirard.bsky.social · 2d

1st desk rejection ! I am very proud of this paper and will persist nevertheless,

Wish me luck (and share the paper widely ! Yes, I am doing shameless self-promotion) !

💪

Chloe Girard, PhD @chloegirard.bsky.social · 7d

🚨 First pre-print from my team !!

TL;DR: presence of polymorphism (sequence differences between the homologous chromosomes) can *increase* the local rate of recombination in Arabidopsis thaliana, turning cold regions of the genome hot (purple v. grey) !

The recombination frequency (cM/Mb) along chromosome 4 of A. thaliana (female meiosis).

In full hybrids (grey), where polymorphism is distributed all along chromosomes, most crossovers occur in the regions surrounding the Centromere (Cen), and very few at chromosome ends (Tel: telomeres).

In lines where polymorphism is restricted to chromosome ends (purple), the local recombination rate increases drastically, at the expense of the non-polymorphic regions (yellow).

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Reposted by Chloe Girard, PhD

Nature @nature.com · 8d

Nature research paper: Holliday junction–ZMM protein feedback enables meiotic crossover assurance

go.nature.com/42JHXnV

Holliday junction–ZMM protein feedback enables meiotic crossover assurance - Nature

Holliday junctions maintain chromosome synapsis to enable crossover assurance in budding yeast.

go.nature.com

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Reposted by Chloe Girard, PhD

Marie Monniaux @mariemonniaux.bsky.social · 6d

Wow this is quite amazing - I know almost nothing on recombination, but always assumed that the more similar the sequences were, the more likely they would recombine, turns out it's the opposite!

Chloe Girard, PhD @chloegirard.bsky.social · 7d

🚨 First pre-print from my team !!

TL;DR: presence of polymorphism (sequence differences between the homologous chromosomes) can *increase* the local rate of recombination in Arabidopsis thaliana, turning cold regions of the genome hot (purple v. grey) !

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Chloe Girard, PhD @chloegirard.bsky.social · 6d

Oh I’m so glad! They say don’t meet your idole, but I wish I was downtown to have a chance to cross you in the street (without recognizing you, else you talked in a mic I guess!)

Enjoy!!!

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Chloe Girard, PhD @chloegirard.bsky.social · 6d

Awww you’re in Paris! Welcome! Hope you enjoy your stay!

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Chloe Girard, PhD @chloegirard.bsky.social · 6d

In Arabidopsis at least! And plants probably (maize shows the same trend, although the genome-wide effect hasn’t been look at yet)
Happy to see you like it 🤓

Chloe Girard, PhD @chloegirard.bsky.social · 7d

Always feels good to get independent confirmation right? Science rules! Thanks for your support Piotr!

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

Thank you Takashi! It’s been long in the work

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

Merci Yann!! Je suis super contente de ce papier!

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

Thanks Max! Now let’s hope it finds a good home 🤓

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

This work couldn’t have been done without the amazing #meiosis4ever community, who first supported the @agencerecherche.bsky.social
grant for this work

I am also very grateful for the guidance of @raphmercier.bsky.social, Eric Jencewski, Julie Clément, Mathilde Grelon, and Bertrand Llorente ❤️🧬

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

This is the work of a tremendous PhD student, Benoit Madec, who did everything in this study (genetics, molecular biology, all the bioinformatics analyses)

He defended his PhD on Monday and is now Dr Madec!

I am very proud of him and all the work he has accomplished!

Benoît during his PhD defense on Monday!

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

To read the full story, head out here:

www.biorxiv.org/content/10.1...

Any and all comments are appreciated !

Polymorphism can extensively reshape the genome-wide crossover landscape in Arabidopsis thaliana

Meiotic recombination, via the formation of crossovers (COs), re-assorts parental alleles and dictate which traits are inherited together, or not. The recombination rate is not homogeneous across the ...

www.biorxiv.org

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

Ok but so what do you think is happening?!

We propose a model in which presence of polymorphism is a major driver of recombination in A. thaliana, totally reshaping the crossover landscape, and competing with other rec. drivers that usually favor crossovers in the pericentromeric "HRZ" regions.

Our model:

Left: in full hybrids (or fully homozygous lines for that matter, check out Raphaël Mercier's work Lian et al., 2022), most crossovers occur around the centromeres, promoted by unknown recombination drivers (although we have a few hypotheses!!).

Right: in cases where recombination has the choice, crossovers are favored in polymorphic regions (purple) at the expense of non-polymorphic ones (yellow).

We also discuss the role of crossover interference (dint) in shaping the crossover landscape, whose strength is unchanged in the two situations, but whose effect can amplify the differences cause by the presence of polymorphism.

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

How is this happening ?

Recombination involves the invasion of an intact matrix by a broken DNA molecule. If the sequence of the two DNA molecules differes, this can create mismatches, recognized by the MMR (mismatch repair)/

The MMR protein MSH2 is required for COs to form in polymorphic regions.

Top: Recombination Rate (cM/Mb) on chromosome 3 of A. thaliana, in both WT and msh2 mutant lines. Yellow: non-polymorphic regions, Purple: polymorphic regions. Dashed line: Centromere

Bottom: recombination rate across the genome in both WT and msh2, in all polymorphic regions (purple, left) and non-polymorphic ones (yellow, left) of the genome.

We observe that the recombination rate is lower in msh2 than in WT in polymorphic regions, but the opposite is true in non-polymorphic ones.

This suggests that MSH2 drives recombination to polymorphic regions.

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

What is fantastic about this discovery?

Not only do we turn cold region of the genome hot, but we also turn hot regions cold !

Case and point: the High-Recombination Zone (HRZ) that flanks the centeromeres in A. thaliana can be depleted of crossovers (see also Fig 1 above).

Recombination Rate (cM/Mb) on chromosome 2 of A. thaliana (male meiosis).

When non-polymorphic (yellow), the HRZ (high-recombination zone) sees its recombination rate decrease compared to full F1 hybrids (grey, where polymorphism is distributed all along the chromosomes).

This is due to the fact that a polymorphic region (purple) is present on the arm of the chromosome, which promotes local recombination, at the expense of the HRZ.

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

And what do we see ?

Always higher recombination in polymorphic regions (heterozygous, purple), than in non-polymorphic ones (homozygous, yellow).

This is true in male and female meiosis, across the genome, independently of other genomic features.

Top: recombination rate (RR) across chromosomes 4 of A. thaliana. Purple: RR when the region is polymorphic (Heterozygous)
Yellow: RR when the region is non-polymorphic (Homozygous)
Grey: Centromeric region.
Pale blue: Pericentromeres, as defined by DNA methylation levels.

Bottom: Normalized total number of crossovers per region, the darker the color palette, the more COs.

When a region is heterozygous (polymorphic, purple) , the recombination rate is higher than when the same region is homozygous (non polymorphic, yellow).

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

How did we figure this out?

We used Recombinant Inbred Lines, which genomes are a patchwork of two parental genomes. After many generations of inbreeding, these lines are now homozygous.

We backcrossed the RIL to its parents, and measured recombination genome-wide in both crosses.

Experimental design: a Recombinant Inbred Line (RIL, top) is crossed to its original parents (Catania-1 and Columbia-0). This produces two lines (bottom) in which some regions are polymorphic, and some are not.

Because we performed both crosses, we can measure crossovers (COs) in each region under its polymorphic (purple) or non-polymorphic state (yellow).

We also analyzed male and female meiosis independently for both reciprocal crosses.

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

Why is this important ? (cont.)

This seems to be conserved in plants (check out @piotraz.bsky.social 's work in maize!).

It could be important in selfing plants, in which genomes tend to become homozygous over generations.

--> The effect we describe could mitigate this loss of diversity.

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

Why is this important ?

Recombination is a homology based mechanism, and detection of differences between DNA molecules engaged in recombination is crucial to avoid genome rearrangements.

BUT low levels of divergence (0.4%, 1 SNP/250pb) can actually promote recombination (crossover formation)

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Chloe Girard, PhD @chloegirard.bsky.social · 7d

🚨 First pre-print from my team !!

TL;DR: presence of polymorphism (sequence differences between the homologous chromosomes) can *increase* the local rate of recombination in Arabidopsis thaliana, turning cold regions of the genome hot (purple v. grey) !

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Chloe Girard, PhD @chloegirard.bsky.social · 14d

@ccilelorrain.bsky.social @cecilesauvanet.bsky.social @boulayac.bsky.social @cecilecourret.bsky.social @annesofio.bsky.social
@ksiudeja.bsky.social @ambresala.bsky.social

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Chloe Girard, PhD @chloegirard.bsky.social · 19d

Paper submitted! Not rejected yet!! Celebration is required 🥳

Thread will come as soon as it appears on BioRxiv

🥂

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Chloe Girard, PhD @chloegirard.bsky.social · 21d

I was about to say the same. KASP can become cheaper but you need to establish the markers, but so do you with micro sat. I don’t have a better solution, let’s hope the hive mind does!

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Chloe Girard, PhD @chloegirard.bsky.social · Jul 19

Aahhhhh c’est cool qu’ils aient eu la cover!! 7 ans sur BioRxiv

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