sequencing neanderthal dna lauren edelson. road map sequencing ancient dna: methods & outcomes...
TRANSCRIPT
![Page 1: Sequencing Neanderthal DNA Lauren Edelson. Road Map Sequencing ancient DNA: methods & outcomes (Review article) DNA sequencing to infer Neanderthal ancestry](https://reader030.vdocument.in/reader030/viewer/2022020111/56649d125503460f949e5b31/html5/thumbnails/1.jpg)
Sequencing Neanderthal DNA
Lauren Edelson
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Road Map• Sequencing ancient DNA:
methods & outcomes (Review article)
• DNA sequencing to infer Neanderthal ancestry in modern humans (Sankararaman et al)
• Examining the Altai Neanderthal population in depth (Prüfer et al)
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Learning About Human Population History From Ancient And Modern Genomes (Review, 2011)
Mark Stoneking and Johannes Krause
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High-throughput sequencing of ancient DNA
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Challenges of sequencing ancient DNA• Repairing damaged DNA
• Avoiding contaminant DNA
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Challenges of sequencing ancient DNA• Post-mortem chemical damage
(continued)
We can use cytosine deamination to test the authenticity of ancient DNA sequences!
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Okay, so we sequenced some Neanderthal DNA.
What now?
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How much can you actually tell from ancient DNA?
• Genetic composition of organisms
• Phylogenetic relationships • Divergence times• Population structure• Population hybridization• Population bottlenecks• Phylogeographic patterns
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Emerging technologies allow for more complex population divergence models
Our best models as of 2009 for population divergence
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SNP data used to compare possible dispersal route scenarios
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Key Dates
• Neanderthal/Denisovan split with humans: 820,000 ya (350,000 ya?)
• Neanderthal and Denisovan split: 680,000 ya• Out of Africa: 50,000 ya• Further human population divergence: 35-
50ya
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The genomic landscape of Neanderthal ancestry in present-day humans (March 2014)
Sriram Sankararaman et al
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Subjects
1004 modern humans–176 West African
(Yoruba tribe: Ibadan, Nigeria)–758 Europeans–572 east-Asians
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Three features of genetic information
1. Allelic pattern at SNPs
2. High sequence divergence
3. Haplotype length
These features are then used to generate a Conditional Random Field (CRF)!
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Conditional Random Fields (CRFs)
• Based on “3 features”• Used to predict likelihood of Neanderthal
ancestry in a given DNA sequence• Feature functions
1. Single SNP in Africans vs Europeans vs Test2. Multiple SNPs used to capture ancestry
(divergence)
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Tiling path from inferred Neanderthal Haplotypes
Average contig lengthChromosome 9 in several Europeans
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Maps of Neanderthal Ancestry
EuropeanEast AsianAfrican
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Neanderthal Ancestry in 1000 modern genomes
EuropeanEast Asian
High selection against Neanderthal DNA on X chromosome
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Male hybrid sterility
• After crossing two species, offspring are often infertile, keeping the two species distinct
• Evidence for this in humans and Neanderthals? Yes!
• But it’s not the only factor causing selection against Neanderthal genome
Male donkey Female horse Mule (infertile)
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B statistic
• Background selection (B) value “indicates the expected fraction of neutral diversity that is present at a site”
• Ranges from 0-1
• Relatively obscure“Widespread Genomic Signatures of Natural Selection in Hominid Evolution”
(McVicker et al, 2009)
Values near 1: little effect of selection
Values near 0:Almost all diversity removed by selection
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Functionally important regions are deficient in Neanderthal ancestry
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Neanderthal GWAS
Genome-Wide Association Studies (GWAS) can be used to associate Neanderthal-derived alleles with modern phenotypes
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Genome-wide estimates of Neanderthal ancestry
• Neanderthal ancestry: east-Asian > European• Larger European population: less time for
selection to remove deleterious alleles
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The complete genome sequence of a Neanderthal from the Altai Mountains(January 2014) Kay Prüfer et al
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Phylogenetic relationships of the Altai Neanderthal
Modern humans Neanderthals
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Homozygosity
• Inheriting identical copies of the same gene from each parent
• Eg Tay-Sachs (from population bottleneck)
• Long runs of homozygosity indicate inbreeding
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Indications of Inbreeding in Altai Neanderthal individual
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Heterozygosity estimates by group
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Inference of population size change over time
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Possible model of gene flow
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Remember this guy?
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Possible model of gene flow
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Takeaways
• Although major challenges exist, it is possible to accurately sequence ancient DNA with modern technology
• We can use these methods to compare ancient and modern DNAAll non-African modern day humans have a small genetic presence of Neanderthal ancestry
• We can learn much about ancient populations (eg bottlenecks & inbreeding of Altai Neanderthals) by looking solely at one bone fragment!
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QUESTIONS?thank you