Evolutionary and Medical Consequences of Archaic Introgression into Modern Human Genomes

Dolgova, Olga; Lao, Oscar

doi:10.3390/genes9070358

“…If fixed differences with a single outgroup are unavailable (for instance if different outgroup species were used to polarize polymorphic sites), then the test can also be set up without fixed differences, by using probabilities p X ' ;n from Eq (7) in Eq (14) and p 0 X ' ;n ða; d ' ; DÞ from Eq (10) in Eq (15).…”

Section: Plos Geneticsmentioning

confidence: 99%

“…Well-documented examples cover a wide range of taxa, including the transfer of wing-pattern mimicry genes in Heliconius butterflies [7], herbivore resistance and abiotic tolerance genes in wild sunflowers [8,9], pesticide resistance in mice [10] and mosquitoes [11], and new mating and vegetative incompatibility types in an invasive fungus [12]. Such adaptive introgressions also occurred in modern humans [13][14][15]: local adaptation to hypoxia at high-altitude was shown to be associated with selection for a Denisovanrelated haplotype at the EPAS1 hypoxia pathway gene in Tibetan populations [16]; positive selection has been characterized for three archaic haplotypes, independently introgressed from Denisovans or Neanderthals in a cluster of genes involved in the innate immune response [17], and immunity related genes show evidence of selection for Neanderthal and Denisovan haplotypes [18,19].…”

Section: Introductionmentioning

confidence: 99%

VolcanoFinder: Genomic scans for adaptive introgression

Setter

¹

,

Mousset

²

,

Cheng

³

et al. 2020

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Recent research shows that introgression between closely-related species is an important source of adaptive alleles for a wide range of taxa. Typically, detection of adaptive introgression from genomic data relies on comparative analyses that require sequence data from both the recipient and the donor species. However, in many cases, the donor is unknown or the data is not currently available. Here, we introduce a genome-scan method-VolcanoFinder-to detect recent events of adaptive introgression using polymorphism data from the recipient species only. VolcanoFinder detects adaptive introgression sweeps from the pattern of excess intermediate-frequency polymorphism they produce in the flanking region of the genome, a pattern which appears as a volcano-shape in pairwise genetic diversity. Using coalescent theory, we derive analytical predictions for these patterns. Based on these results, we develop a composite-likelihood test to detect signatures of adaptive introgression relative to the genomic background. Simulation results show that VolcanoFinder has high statistical power to detect these signatures, even for older sweeps and for soft sweeps initiated by multiple migrant haplotypes. Finally, we implement VolcanoFinder to detect archaic introgression in European and sub-Saharan African human populations, and uncovered interesting candidates in both populations, such as TSHR in Europeans and TCHH-RPTN in Africans. We discuss their biological implications and provide guidelines for identifying and circumventing artifactual signals during empirical applications of VolcanoFinder.

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“…Indeed, recent studies have brought 6 clear evidence of cross-species introgression of advantageous alleles [3-6].7 Well-documented examples cover a wide range of taxa, including the transfer of 8 wing-pattern mimicry genes in Heliconius butterflies [7], herbivore resistance and abiotic 9tolerance genes in wild sunflowers [8,9], pesticide resistance in mice [10] and 10 mosquitoes [11], and new mating and vegetative incompatibility types in an invasive 11 fungus [12]. Such adaptive introgressions also occurred in modern humans [13][14][15]: local 12 adaptation to hypoxia at high-altitude was shown to be associated with selection for a 13 July 10, 2019 2/96 Denisovan-related haplotype at the EPAS1 hypoxia pathway gene in Tibetan 14 populations [16]; positive selection has been characterized for three archaic haplotypes, 15 independently introgressed from Denisovans or Neanderthals in a cluster of genes 16 involved in the innate immune response [17], and immunity related genes show evidence 17 of selection for Neanderthal and Denisovan haplotypes [18, 19]. 18 In all examples above, evidence of adaptive introgression rests on a comparative 19 analysis of DNA from both donor and recipient species.…”

mentioning

confidence: 99%

VolcanoFinder: genomic scans for adaptive introgression

Setter

¹

,

Mousset

²

,

Cheng

³

et al. 2019

Preprint

View full text Add to dashboard Cite

Recent research shows that introgression between closely-related species is an important source of adaptive alleles for a wide range of taxa. Typically, detection of adaptive introgression from genomic data relies on comparative analyses that require sequence data from both the recipient and the donor species. However, in many cases, the donor is unknown or the data is not currently available. Here, we introduce a genome-scan method-VolcanoFinder-to detect recent events of adaptive introgression using polymorphism data from the recipient species only.VolcanoFinder detects adaptive introgression sweeps from the pattern of excess intermediate-frequency polymorphism they produce in the flanking region of the genome, a pattern which appears as a volcano-shape in pairwise genetic diversity.Using coalescent theory, we derive analytical predictions for these patterns. Based on these results, we develop a composite-likelihood test to detect signatures of adaptive introgression relative to the genomic background. Simulation results show that VolcanoFinder has high statistical power to detect these signatures, even for older sweeps and for soft sweeps initiated by multiple migrant haplotypes. Finally, we implement VolcanoFinder to detect archaic introgression in European and sub-Saharan African human populations, and uncovered interesting candidates in both populations, such as TSHR in Europeans and TCHH -RPTN in Africans. We discuss their biological implications and provide guidelines for identifying and circumventing artifactual signals during empirical applications of VolcanoFinder. Author summaryThe process by which beneficial alleles are introduced into a species from a closely-related species is termed adaptive introgression. We present an analytically-tractable model for the effects of adaptive introgression on non-adaptive genetic variation in the genomic region surrounding the beneficial allele. The result we describe is a characteristic volcano-shaped pattern of increased variability that arises around the positively-selected site, and we introduce an open-source method VolcanoFinder to detect this signal in genomic data. Importantly, VolcanoFinder is a population-genetic likelihood-based approach, rather than a comparative-genomic approach, and can therefore probe genomic variation data from a single population for footprints of adaptive introgression, even from a priori unknown and possibly extinct donor species. 4 exchange of key adaptations between related species, with potentially important 5 implications for our view of the adaptive process. Indeed, recent studies have brought 6 clear evidence of cross-species introgression of advantageous alleles [3-6].7 Well-documented examples cover a wide range of taxa, including the transfer of 8 wing-pattern mimicry genes in Heliconius butterflies [7], herbivore resistance and abiotic 9tolerance genes in wild sunflowers [8,9], pesticide resistance in mice [10] and 10 mosquitoes [11], and new mating and vegetative incompatibility types in an invasive 11 fungus [12]. Su...

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“…These methods permit analyzing the phylogenetic relationships among closely related taxa using a multilocus approach, and the signatures of admixture (the mixing of genomes of different taxa through hybridization) and introgression (the passing of alleles from one parental population to another through hybridization and backcrossing). Several primate studies have reported introgression of neutral (e.g., baboons: Wall et al 2016;howler monkeys: Baiz et al 2018) and advantageous alleles (e.g., Neanderthal/Denisovan into modern humans: Dannemann et al 2016;Dolgova and Lao 2018;Enard and Petrov 2018;Gittelman et al 2016;Racimo et al 2015Racimo et al , 2017 as a consequence of current or ancient hybridization. In some instances, alleles of only a few genes or genomic regions have moved from one species to another, but in other cases introgression has led to the formation of lineages of hybrid origin.…”

Section: )mentioning

confidence: 99%