VolcanoFinder: genomic scans for adaptive introgression

Abstract

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...

Learning the properties of adaptive regions with functional data analysis

“…We find that regardless of the types of statistics used, we classify the majority of the genome as neutral, and classify more of the genome as sweep than as adaptive introgression (Tables S12-S15). Importantly, we find that we are able to recapitulate signals of previously-identified regions of adaptive introgression in the CEU population with SURFDAWave, such as BNC2 (Sankararaman et al, 2014;Racimo et al, 2015) and APOL4 (Setter et al, 2019) (Figures S30 and S31). BNC2 is another gene thought to play a role in human skin color determination (Visser et al, 2014), whereas the gene APOL4 is significantly up-regulated in people diagnosed with schizophrenia (Monajemi et al, 2002).…”

“…Adaptive introgression is a complex form of natural selection that produces genetic diversity footprints distinct from typical selective sweeps (Setter et al, 2019). In both selective sweeps and adaptive introgression, diversity generally decreases surrounding the beneficial mutation.…”

“…Similarly, different modes of positive selection may have on average different patterns. For example, if the crest of the wave extends above the rest position (neutrality), then this may be the signal of adaptive introgression as shown in Setter et al (2019).…”

Genetic signatures of evolutionary rescue by a selective sweep

“…As we move away from the selected site recombination breaks apart these migrant haplotypes, leading to patterns of nucleotide diversity that depend on the migration rate and history of the two populations. If the migration rate is low we should expect an excess of migrant haplotypes at the site of the selective introgression and, if the divergence between the migrant and focal population is high, the so-called "volcano" pattern of diversity (Setter et al, 2019), where diversity is maximized at an intermediate distance from the selected site due to a more balanced presence of both migrant and non-migrant alleles. Evolutionary rescue has been explored theoretically (e.g., Gomulkiewicz and Holt, 1995;Uecker and Hermisson, 2016;Anciaux et al, 2018) and observed repeatedly in both experiments (e.g., Bell and Gonzalez, 2009;Lindsey et al, 2013;Ramsayer et al, 2013) and in host-pathogen systems in nature (e.,g., Wei et al, 1995;Feder et al, 2016).…”

On the distribution of tract lengths during adaptive introgression

“…[13,27]). However, the specific genetic signature of adaptive introgression and its impact on patterns of genetic variation remains less explored (but see e.g., [33]). There is, therefore, a clear need to develop a theoretical framework to investigate the impacts of adaptive introgression on the genomes of natural populations.…”