Application of a novel haplotype-based scan for local adaptation to study high-altitude adaptation in rhesus macaques

Abstract

When natural populations split and migrate to different environments, they may experience different selection pressures that can lead to local adaptation. To capture the genomic patterns of a local selective sweep, we develop XP‐nSL, a genomic scan for local adaptation that compares haplotype patterns between two populations. We show that XP‐nSL has power to detect ongoing and recently completed hard and soft sweeps, and we then apply this statistic to search for evidence of adaptation to high altitude in rhesus macaques. We analyze the whole genomes of 23 wild rhesus macaques captured at high altitude (mean altitude > 4000 m above sea level) to 22 wild rhesus macaques captured at low altitude (mean altitude < 500 m above sea level) and find evidence of local adaptation in the high‐altitude population at or near 303 known genes and several unannotated regions. We find the strongest signal for adaptation at EGLN1, a classic target for convergent evolution in several species living in low oxygen environments. Furthermore, many of the 303 genes are involved in processes related to hypoxia, regulation of ROS, DNA damage repair, synaptic signaling, and metabolism. These results suggest that, beyond adapting via a beneficial mutation in one single gene, adaptation to high altitude in rhesus macaques is polygenic and spread across numerous important biological systems.

A spatially aware likelihood test to detect sweeps from haplotype distributions

“…Many statistics have been proposed to capture these patterns to make inferences about recent or ongoing positive selection [Sabeti et al, 2002, Voight et al, 2006, Sabeti et al, 2007, Ferrer-Admetlla et al, 2014, Garud et al, 2015, Field et al, 2016, Harris et al, 2018, Torres et al, 2018, Stern et al, 2019, Harris and DeGiorgio, 2020, Szpiech et al, 2021, Szpiech, 2021, Kim and Stephan, 2002, Nielsen et al, 2005, Chen et al, 2010, Huber et al, 2015, Vy and Kim, 2015, DeGiorgio et al, 2016, Racimo, 2016, Lee and Coop, 2017, Setter et al, 2020, many of which focus on summarizing patterns of haplotype homozygosity in a local genomic region. A particularly novel approach, the T statistic implemented in LASSI [Harris and DeGiorgio, 2020], employs a likelihood model based on distortions of the haplotype frequency spectrum (HFS).…”

Genomic population structure and local adaptation of the wild strawberry Fragaria nilgerrensis

“…We performed scans on each group separately by using two approaches: (i) a method relying on multiple signatures of a selective sweep via the enumeration of SNP vectors (Raised Accuracy in Sweep Detection, RAiSD) [ 88 ] and (ii) a haplotype-based statistics method (XP-nSL) [ 89 ], which was implemented in Selscan v1.3.0 [ 90 ]. RAiSD collectively utilizes three distinct signatures to detect selective sweeps: local reduction of the polymorphism, the shift in the site frequency spectrum toward low- and high-frequency-derived variants, and the localized pattern of LD [ 88 ].…”

“…XP-nSL summarizes haplotype diversity by calculating the average number of variant sites in a genomic region that are identical across all haplotypes, and then compares haplotype pools between two different populations, which makes it possible to detect differential local adaptation [ 89 ]. XP-nSL was calculated on all nine comparisons of the four groups (for each comparison, using each group once as the objective and once as the reference).…”

Combined approaches identify known and novel genes associated with sheep litter size and non‐seasonal breeding

“…XP‐nSL is a recent cross‐population haplotype‐based statistic developed by Szpiech et␣al . (2021), that aims to detect the signatures of selection on extended genomic segments of low diversity on sweeping haplotypes in a target population vs. a reference population (Szpiech et␣al . 2021).…”

“…XP-nSL is a recent cross-population haplotype-based statistic developed by Szpiech et al (2021), that aims to detect the signatures of selection on extended genomic segments of low diversity on sweeping haplotypes in a target population vs. a reference population (Szpiech et al 2021). To compare the haplotype patterns between sheep breeds with different reproductivity, XP-nSL statistic was used to capture selective sweeps in STH and QB using SNT as the reference, respectively.…”