GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars...
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![Page 1: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/1.jpg)
GSRThe Gene Sequence evolution model
with iid Rate variation over tree
Örjan Åkerborg, KTH
Lars Arvestad, KTH
Jens Lagergren, KTH
Bengt Sennblad
![Page 2: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/2.jpg)
What?
• Gene evolution through duplication and loss
• Sequence evolution
![Page 3: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/3.jpg)
Why?
• Base reconciliation analysis directly on data– Avoid information loss– Addresses uncertainty better
• Gene tree reconstruction should mirror generation
![Page 4: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/4.jpg)
When?
• Arvestad et al. 2003, – MrBayes + GEM– Flawed model
![Page 5: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/5.jpg)
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60s ribosomal data
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• Arvestad et al. 2003, – MrBayes + GEM– Flawed model
• Arvestad et al. 2004 – Intergrated GEM + Substitution model– Mathematically correct model– Molecular clock– Sampling algorithm - slow
When?
![Page 7: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/7.jpg)
MHC revisited
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![Page 8: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/8.jpg)
• Åkerborg et al. Submitted (GSR)– Integrated GEM + SRT model
When?
• Arvestad et al. 2003, – MrBayes + GEM– Flawed model
• Arvestad et al. 2004– Intergrated GEM + Substitution model– Mathematically correct model– Molecular clock– Sampling algorithm - slow
![Page 9: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/9.jpg)
How?
• GSR– GEM
• Reconciled trees – duplication and loss
– SRT• Relaxed clock model (iid)• Substitution model
– Fast algorithm• Discretized time space
![Page 10: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/10.jpg)
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Trees, T
Sequence data, F
Pr[D,T]
Self-consistency
![Page 11: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/11.jpg)
Self-consistency – the X%-test
![Page 12: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/12.jpg)
Application to Yeast data
• Compare to prev. Results– YGOB– Orthogrups (SYNERGY)
• Both synteny-based
![Page 13: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/13.jpg)
Synteny -- gene order
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Application to Yeast data
• Compare to prev. Results– YGOB– Orthogrups (SYNERGY)
• Both synteny-based
– Whole genome duplication• Challenge!
• Genome-wide analysis!– 4809 gene families
(orthogroups)
![Page 15: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/15.jpg)
Comparison YGOB results
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Molecular clock?
![Page 17: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/17.jpg)
Comparison SYNERGY results
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Sequence vs. synteny data
• No sequence diff– 36% of data sets are >85% similar
• Strong divergence– 25% of data set are <40% similar– Long-branch attraction
• Conflicting sequence-synteny signal
![Page 19: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/19.jpg)
Sequence vs. synteny data
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Orthogroup 3176
42.4 %
Single best SYNERGY tree
21.6 %31.6 %
![Page 21: GSR The Gene Sequence evolution model with iid Rate variation over tree Örjan Åkerborg, KTH Lars Arvestad, KTH Jens Lagergren, KTH Bengt Sennblad.](https://reader036.fdocuments.net/reader036/viewer/2022062516/56649d575503460f94a353db/html5/thumbnails/21.jpg)
Summary
• primeGSR– Integrated model
• Reconciliation – gene duplication loss• Relaxed clock• Sequence evolution
– Efficient algorithms– Improved gene tree reconstruction
• Future prospects– Divergence time estimates (MAP)– Species tree reconstruction– Include synteny