Ever wonder what the #3Dgenome folding🔺of a Neanderthal looked like?! Could it hold any clues as to where and why we have DNA 🧬and trait differences?
Check out our @capra_lab, Pollard lab & @gfudenberg lab collaboration @biorxivpreprint biorxiv.org/content/10.110…
1/8
Check out our @capra_lab, Pollard lab & @gfudenberg lab collaboration @biorxivpreprint biorxiv.org/content/10.110…
1/8
Sadly, bc of ancient👴sample degradation, we've never explored the role of the 3D genome in archaic hominins like Neanderthals/Denisovans.
But lucky for us, new deep learning models can infer 3D genome structure from DNA sequence alone (like @gfudenberg & @drklly's Akita).
2/8
But lucky for us, new deep learning models can infer 3D genome structure from DNA sequence alone (like @gfudenberg & @drklly's Akita).
2/8
Using these models, we predict 3D contact maps across Neanderthal, Denisovan, and diverse modern human genomes.
We identify 167 distinct regions with diverged 3D genome organization between archaics and modern humans across the genome!
3/8
We identify 167 distinct regions with diverged 3D genome organization between archaics and modern humans across the genome!
3/8
We show that 3D divergent windows in Neanderthals are enriched nearby genes associated with lots of interesting traits like the eye👀, supra-orbital ridges💀, hair💇, lungs 🫁, immune response💉, and cognition🧠! Provides a putative molecular mech for genotype -> phenotype
4/8
4/8
Despite the differences.. overall, modern human and archaic 3D genomes are more similar than expected, suggesting that the pressure to maintain 3D genome organization constrained hominin sequence evolution. (See the paper for some simulations & details.)
5/8
5/8
We also find that 3D genome organization constrained the landscape of archaic ancestry in humans today: regions more tolerant of 3D variation are enriched for introgression (archaic ancestry) in modern Eurasians.
6/8
6/8
Because we found 3D differences between humans and Neanderthals, we wondered...did humans inherit any of these novel predicted 3D genome structures from our Neanderthal ancestors bc of interbreeding? Spoiler alert: we did! 🤯
7/8
7/8
Lots more with more context + details in the paper. Plenty of limitations and future directions. We hope our deep-learning applications to predict 3D genome folding provides a window 🪟 into previously unobservable molecular mechanisms🧬. Thanks to all collaborators! Enjoy!
8/8
8/8
Artistic phylogeny inspired by Ahlquist, @FerVillanea @KWitt_aDNA et al. GBE 2021 Fig1 (not to scale)!
• • •
Missing some Tweet in this thread? You can try to
force a refresh
