A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Selective sweeps are frequent and varied signatures in the genomes of natural populations, and detecting them is consequently important in understanding mechanisms of adaptation by natural selection. Following a selective sweep, haplotypic diversity surrounding the site under selection decreases, and this deviation from the background pattern of variation can be applied to identify sweeps. Multiple methods exist to locate selective sweeps in the genome from haplotype data, but none leverage the power of a model-based approach to make their inference. Here, we propose a likelihood ratio test statistic T to probe whole genome polymorphism datasets for selective sweep signatures. Our framework uses a simple but powerful model of haplotype frequency spectrum distortion to find sweeps and additionally make an inference on the number of presently sweeping haplotypes in a population. We found that the T statistic is suitable for detecting both hard and soft sweeps across a variety of demographic models, selection strengths, and ages of the beneficial allele. Accordingly, we applied the T statistic to variant calls from European and sub-Saharan African human populations, yielding primarily literature-supported candidates, including LCT, RSPH3, and ZNF211 in CEU, SYT1, RGS18, and NNT in YRI, and HLA genes in both populations. We also searched for sweep signatures in Drosophila melanogaster, finding expected candidates at Ace, Uhg1, and Pimet. Finally, we provide open-source software to compute the T statistic and the inferred number of presently sweeping haplotypes from whole-genome data.

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“…2007 ). Additionally, selection on collagen-related genes has been implicated in cold adaptations in European populations ( Yudin et al. 2017 ).…”

Section: Resultsmentioning

confidence: 99%

A Likelihood Approach for Uncovering Selective Sweep Signatures from Haplotype Data

Harris

DeGiorgio

2020

Molecular Biology and Evolution

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“…The tool allows detection of enriched terms from Gene Ontology and biological pathways or models for a variety of biological processes presented in the REACTOME, KEGG, and BIOCARTA. The benefits of using the ontological and pathway analyses for functional annotation of genes harboring SNPs, associated with various traits, have been confirmed in numerous publications [62–66].…”

Section: Methodsmentioning

confidence: 99%

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population

et al. 2019

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Background Tick-borne encephalitis (TBE) is a viral infectious disease caused by tick-borne encephalitis virus (TBEV). TBEV infection is responsible for a variety of clinical manifestations ranging from mild fever to severe neurological illness. Genetic factors involved in the host response to TBEV that may potentially play a role in the severity of the disease are still poorly understood. In this study, using whole-exome sequencing, we aimed to identify genetic variants and genes associated with severe forms of TBE as well as biological pathways through which the identified variants may influence the severity of the disease. Results Whole-exome sequencing data analysis was performed on 22 Russian patients with severe forms of TBE and 17 Russian individuals from the control group. We identified 2407 candidate genes harboring rare, potentially pathogenic variants in exomes of patients with TBE and not containing any rare, potentially pathogenic variants in exomes of individuals from the control group. According to DAVID tool, this set of 2407 genes was enriched with genes involved in extracellular matrix proteoglycans pathway and genes encoding proteins located at the cell periphery. A total of 154 genes/proteins from these functional groups have been shown to be involved in protein-protein interactions (PPIs) with the known candidate genes/proteins extracted from TBEVHostDB database. By ranking these genes according to the number of rare harmful minor alleles, we identified two genes ( MSR1 and LMO7), harboring five minor alleles, and three genes ( FLNA, PALLD, PKD1 ) harboring four minor alleles. When considering genes harboring genetic variants associated with severe forms of TBE at the suggestive P -value < 0.01, 46 genes containing harmful variants were identified. Out of these 46 genes, eight ( MAP4, WDFY4, ACTRT2, KLHL25, MAP2K3, MBD1, OR10J1, and OR2T34) were additionally found among genes containing rare pathogenic variants identified in patients with TBE; and five genes ( WDFY4 , ALK, MAP4, BNIPL, EPPK1 ) were found to encode proteins that are involved in PPIs with proteins encoded by genes from TBEVHostDB. Three genes out of five ( MAP4, EPPK1, ALK ) were found to encode proteins located at cell periphery. Conclusions Whole-exome sequencing followed by systems biology approach enabled to identify eight candidate genes ( MAP4, WDFY4, ACTRT2, KLHL25, MAP2K3, MBD1, OR10J1, and OR2T34 ) that can potentially determine predisposition to severe forms of TBE. Analyses of the genetic risk factors for severe forms of TBE revealed a significant enrichment with genes controlling extracellular matrix proteoglycans pathway as well...

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“…Notably, none of the seven pathways showed significant enrichment in modern populations, implying that admixture has also obscured these signals in modern genomes. Four of the metabolic pathways shared across multiple ancient populations ( Figure 5) are collagen specific -a metabolic process that has been shown to be a frequent target of selection in mammals living in circumpolar regions (Yudin et al, 2017). In addition, six of the eight sweeps with either a single gene or a single biological process are Ancestral West Eurasian (>35kya), and are either involved in lipid metabolism (two sweeps) or with nervous tissue maintenance (four sweeps) (Material and Methods), both of which have been associated with adaptation to cold environments (Brandefelt et al, 2011;Daló et al, 2007;Nedergaard and Cannon, 2018).…”

Section: Adaptation To Temperate Paleolithic Eurasian Environmentsmentioning

confidence: 99%

Admixture has obscured signals of historical hard sweeps in humans

Souilmi

Tobler

Johar

et al. 2020

Preprint

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The role of selection in shaping genetic diversity in natural populations is an area of intense interest in modern biology, especially the characterization of adaptive loci.Within humans, the rapid increase in genomic information has produced surprisingly few well-defined adaptive loci, promoting the view that recent human adaptation involved numerous loci with small fitness benefits. To examine this we searched for signatures of hard sweeps -the selective fixation of a new or initially rare beneficial variant -in 1,162 ancient western Eurasian genomes and identified 57 sweeps with high confidence. This unexpectedly extensive signal was concentrated on proteins acting at the cell surface, and potential selection pressures include cold adaptation in early Eurasian populations, and oxidative stress from carbohydrate-rich diets in farming populations. Critically, these sweep signals have been obscured in modern European genomes by subsequent population admixture, especially during the Bronze Age (5-3kya) and empires of classical antiquity.

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A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Cited by 39 publications

References 86 publications

A Likelihood Approach for Uncovering Selective Sweep Signatures from Haplotype Data

A Likelihood Approach for Uncovering Selective Sweep Signatures from Haplotype Data

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population

Admixture has obscured signals of historical hard sweeps in humans

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