Zachary Baker

Evolutionary biologist, interested in meiosis, recombination and comparative phylogenetics.

[Zachary Baker @ZachTWBaker]

The full version of our paper on the evolution of the PRDM9 and its binding sites, in light of the importance of symmetric PRDM9 binding, is now available online https://t.co/hcdBSlovhu

[Zachary Baker @ZachTWBaker]

@spence_jeffrey_ @GuyS2747 @molly_przew Of course, we also assume that each PRDM9-bound site is equally like to experience a DSB. In reality, DSB heats would be influenced by PRDM9 binding heats and other factors (e.g., ATM, as in Paiano et al. 2020).

[Zachary Baker @ZachTWBaker]

@GuyS2747 @molly_przew Happy to share our preprint addressing the question of why PRDM9 binding and the recombination hotspot landscape evolve so rapidly: https://t.co/fHIuYlTArB

[Zachary Baker @ZachTWBaker]

@spence_jeffrey_ @GuyS2747 @molly_przew For simplicity, we modeled 'cold alleles' as sites wherein a binding motif had been completely disrupted by mutation. But all that is crucial for our model is that the allelic variation in heats is caused, one way or another, by local sequence variation.

[Zachary Baker @ZachTWBaker]

@WTF_R_species @GuyS2747 @molly_przew My own personal hypothesis is that it likely gained such a role even earlier, if only because it seems all the pieces to do so are in place.

[Zachary Baker @ZachTWBaker]

@WTF_R_species @GuyS2747 @molly_przew However, the evidence for co-evolution of PRDM9 with ZCWPW1 within fish (Cavissim et al 2022) suggests that PRDM9 has likely been playing a role since at least the ancestor of bony vertebrates.

[Zachary Baker @ZachTWBaker]

By extension, we suggest that the evolutionary advantage of hotspots may be to increase the efficiency of DSB repair and/or homolog pairing through the symmetric recruitment of factors involved in both DSB initiation and repair.

[Zachary Baker @ZachTWBaker]

New PRDM9 alleles restore binding sites. But they are favored not because they increase PRDM9 binding, as previously argued, but because they limit the number of binding sites that are used and thereby increase symmetric binding.

[Zachary Baker @ZachTWBaker]

@izabelcavassim @lichtenmj Another possibility is that the association stems more indirectly from TEX15's role in the piRNA pathway. Methylation of TEs prevents their use as sites of recombination in mice (eg, Zamudio et al 2015). Might be that TEX15 is important for preventing PRDM9 binding to TEs.

[Zachary Baker @ZachTWBaker]

@FlorianLabourel @molly_przew @izabelcavassim I think the simplest explanation is just that the mammalian losses of PRDM9 are the most recent losses. We still find various degrees of evidence for reduced constraint in these lineages, eg, for both ZCWPW genes in platypus and for ZCWPW2 in canids.