@article {318063,
	title = {Limits of long-term selection against Neandertal introgression},
	journal = {Proceedings of the National Academy of Sciences},
	year = {2019},
	month = {2019/01/15},
	pages = {201814338},
	abstract = {<p>Since the discovery that all non-Africans inherit 2\% of their genomes from Neandertal ancestors, there has been a great interest in understanding the fate and effects of introgressed Neandertal DNA in modern humans. A number of recent studies have claimed that there has been continuous selection against introgressed Neandertal DNA over the last 55,000 years. Here, we show that there has been no long-term genome-wide removal of Neandertal DNA, and that the previous result was due to incorrect assumptions about gene flow between African and non-African populations. Nevertheless, selection did occur following introgression, and its effect was strongest in regulatory regions, suggesting that Neandertals may have differed from humans more in their regulatory than in their protein-coding sequences.Several studies have suggested that introgressed Neandertal DNA was subjected to negative selection in modern humans. A striking observation in support of this is an apparent monotonic decline in Neandertal ancestry observed in modern humans in Europe over the past 45,000 years. Here, we show that this decline is an artifact likely caused by gene flow between modern human populations, which is not taken into account by statistics previously used to estimate Neandertal ancestry. When we apply a statistic that avoids assumptions about modern human demography by taking advantage of two high-coverage Neandertal genomes, we find no evidence for a change in Neandertal ancestry in Europe over the past 45,000 years. We use whole-genome simulations of selection and introgression to investigate a wide range of model parameters and find that negative selection is not expected to cause a significant long-term decline in genome-wide Neandertal ancestry. Nevertheless, these models recapitulate previously observed signals of selection against Neandertal alleles, in particular the depletion of Neandertal ancestry in conserved genomic regions. Surprisingly, we find that this depletion is strongest in regulatory and conserved noncoding regions and in the most conserved portion of protein-coding sequences.</p>
},
	doi = {https://doi.org/10.1073/pnas.1814338116},
	url = {https://www.pnas.org/content/early/2019/01/14/1814338116},
	author = {Petr, Martin and P{\"a}{\"a}bo, Svante and Kelso, Janet and Vernot, Benjamin}
}
