scholarly journals Signatures of long-term balancing selection in human genomes

2017 ◽  
Author(s):  
Bárbara Domingues Bitarello ◽  
Cesare de Filippo ◽  
João Carlos Teixeira ◽  
Joshua M. Schmidt ◽  
Philip Kleinert ◽  
...  
Keyword(s):  
Balancing Selection ◽  
Theoretical Perspective ◽  
Human Populations ◽  
Protein Coding ◽  
Human Genomes ◽  
Genome Wide ◽  
Higher Power ◽  
Genome Wide Data ◽  
Immune Related Genes

AbstractBalancing selection maintains advantageous diversity in populations through various mechanisms. While extensively explored from a theoretical perspective, an empirical understanding of its prevalence and targets lags behind our knowledge of positive selection. Here we describe the Non-Central Deviation (NCD), a simple yet powerful statistic to detect long-term balancing selection (LTBS) that quantifies how close frequencies are to expectations under LTBS, and provides the basis for a neutrality test. NCD can be applied to a single locus or genomic data, and can be implemented considering only polymorphisms (NCD1) or also considering fixed differences with respect to an outgroup (NCD2) species. Incorporating fixed differences improves power, and NCD2 has higher power to detect LTBS in humans under different frequencies of the balanced allele(s) than other available methods. Applied to genome-wide data from African and European human populations, in both cases using chimpanzee as an outgroup, NCD2 shows that, albeit not prevalent, LTBS affects a sizable portion of the genome: about 0.6% of analyzed genomic windows and 0.8% of analyzed positions. Significant windows (p < 0.0001) contain 1.6% of SNPs in the genome, which disproportionally fall within exons and change protein sequence, but are not enriched in putatively regulatory sites. These windows overlap about 8% of the protein-coding genes, and these have larger number of transcripts than expected by chance even after controlling for gene length. Our catalog includes known targets of LTBS but a majority of them (90%) are novel. As expected, immune-related genes are among those with the strongest signatures, although most candidates are involved in other biological functions, suggesting that LTBS potentially influences diverse human phenotypes.

scholarly journals Evolutionary and Medical Consequences of Archaic Introgression into Modern Human Genomes

Genes ◽  
2018 ◽  
Vol 9 (7) ◽  
pp. 358 ◽  
Author(s):  
Olga Dolgova ◽  
Oscar Lao
Keyword(s):  
Demographic History ◽  
Modern Human ◽  
Human Populations ◽  
Human Genomes ◽  
Fitness Consequences ◽  
Genome Wide ◽  
Anatomically Modern Humans ◽  
Genome Wide Data ◽  
History Of ◽  
Health And Disease

The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered. It is currently known that AMH interbred with archaic hominins once they left the African continent. Current non-African human genomes carry fragments of archaic origin. This review focuses on the fitness consequences of archaic interbreeding in current human populations. We discuss new insights and challenges that researchers face when interpreting the potential impact of introgression on fitness and testing hypotheses about the role of selection within the context of health and disease.

scholarly journals Evolutionary and Medical Consequences of Archaic Introgression into Modern Human Genomes

2018 ◽  
Author(s):  
Olga Dolgova ◽  
Oscar Lao
Keyword(s):  
Demographic History ◽  
Modern Human ◽  
Human Populations ◽  
Human Genomes ◽  
Fitness Consequences ◽  
Genome Wide ◽  
Anatomically Modern Humans ◽  
Genome Wide Data ◽  
History Of ◽  
Health And Disease

The demographic history of anatomically modern humans (AMH) involves multiple migration events, population extinctions and genetic adaptations. As genome-wide data from complete genome sequencing becomes increasingly abundant and available even from extinct hominins, new insights of the evolutionary history of our species are discovered. It is currently known that AMH introgressed with archaic hominins once they left the African continent. Current out of African human genomes carry fragments of archaic origin. This review focuses on the fitness consequences of archaic interbreeding in current human populations. We discuss new insights and challenges that researchers face when interpreting the potential impact of introgression on fitness and testing hypotheses about the role of selection within the context of health and disease.

scholarly journals A curated dataset of modern and ancient high-coverage shotgun human genomes

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pierpaolo Maisano Delser ◽  
Eppie R. Jones ◽  
Anahit Hovhannisyan ◽  
Lara Cassidy ◽  
Ron Pinhasi ◽  
...  
Keyword(s):  
Sequence Data ◽  
Whole Genome ◽  
Reference Dataset ◽  
High Coverage ◽  
Sample Distribution ◽  
Human Samples ◽  
Human Genomes ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Computationally Intensive

AbstractOver the last few years, genome-wide data for a large number of ancient human samples have been collected. Whilst datasets of captured SNPs have been collated, high coverage shotgun genomes (which are relatively few but allow certain types of analyses not possible with ascertained captured SNPs) have to be reprocessed by individual groups from raw reads. This task is computationally intensive. Here, we release a dataset including 35 whole-genome sequenced samples, previously published and distributed worldwide, together with the genetic pipeline used to process them. The dataset contains 72,041,355 sites called across 19 ancient and 16 modern individuals and includes sequence data from four previously published ancient samples which we sequenced to higher coverage (10–18x). Such a resource will allow researchers to analyse their new samples with the same genetic pipeline and directly compare them to the reference dataset without re-processing published samples. Moreover, this dataset can be easily expanded to increase the sample distribution both across time and space.

scholarly journals Population genetics of the coral Acropora millepora: Towards a genomic predictor of bleaching

2019 ◽  
Author(s):  
Zachary L. Fuller ◽  
Veronique J.L. Mocellin ◽  
Luke Morris ◽  
Neal Cantin ◽  
Jihanne Shepherd ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Balancing Selection ◽  
Genome Wide Association ◽  
Conservation Strategies ◽  
Genome Sequences ◽  
Acropora Millepora ◽  
Genome Wide ◽  
A Genome ◽  
In The Wild

AbstractAlthough reef-building corals are rapidly declining worldwide, responses to bleaching vary both within and among species. Because these inter-individual differences are partly heritable, they should in principle be predictable from genomic data. Towards that goal, we generated a chromosome-scale genome assembly for the coral Acropora millepora. We then obtained whole genome sequences for 237 phenotyped samples collected at 12 reefs distributed along the Great Barrier Reef, among which we inferred very little population structure. Scanning the genome for evidence of local adaptation, we detected signatures of long-term balancing selection in the heat-shock co-chaperone sacsin. We further used 213 of the samples to conduct a genome-wide association study of visual bleaching score, incorporating the polygenic score derived from it into a predictive model for bleaching in the wild. These results set the stage for the use of genomics-based approaches in conservation strategies.

scholarly journals Genotyping common, large structural variations in 5,202 genomes using pangenomes, the Giraffe mapper, and the vg toolkit

2020 ◽  
Author(s):  
Jouni Sirén ◽  
Jean Monlong ◽  
Xian Chang ◽  
Adam M. Novak ◽  
Jordan M. Eizenga ◽  
...  
Keyword(s):  
Human Populations ◽  
Structural Variations ◽  
Single Nucleotide ◽  
Human Genomes ◽  
Genome Wide ◽  
Sequence Graph ◽  
Long Read ◽  
Comparable Accuracy ◽  
Single Nucleotide Variations ◽  
Allelic Variations

ABSTRACTWe introduce Giraffe, a pangenome short read mapper that can efficiently map to a collection of haplotypes threaded through a sequence graph. Giraffe, part of the variation graph toolkit (vg)1, maps reads to thousands of human genomes at around the same speed BWA-MEM2 maps reads to a single reference genome, while maintaining comparable accuracy to VG-MAP, vg’s original mapper. We have developed efficient genotyping pipelines using Giraffe. We demonstrate improvements in genotyping for single nucleotide variations (SNVs), insertions and deletions (indels) and structural variations (SVs) genome-wide. We use Giraffe to genotype and phase 167 thousands structural variations ascertained from long read studies in 5,202 human genomes sequenced with short reads, including the complete 1000 Genomes Project dataset, at an average cost of $1.50 per sample. We determine the frequency of these variations in diverse human populations, characterize their complex allelic variations and identify thousands of expression quantitative trait loci (eQTLs) driven by these variations.

scholarly journals Interaction between M. tuberculosis Lineage and Human Genetic Variants Reveals Novel Pathway Associations with Severity of TB

Pathogens ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1487
Author(s):  
Michael L. McHenry ◽  
Eddie M. Wampande ◽  
Moses L. Joloba ◽  
LaShaunda L. Malone ◽  
Harriet Mayanja-Kizza ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Clinical Presentation ◽  
Sub Saharan Africa ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Human Genomes ◽  
Genome Wide ◽  
Sub Saharan ◽  
Cellular Replication

Tuberculosis (TB) remains a major public health threat globally, especially in sub-Saharan Africa. Both human and Mycobacterium tuberculosis (MTBC) genetic variation affect TB outcomes, but few studies have examined if and how the two genomes interact to affect disease. We hypothesize that long-term coexistence between human genomes and MTBC lineages modulates disease to affect its severity. We examined this hypothesis in our TB household contact study in Kampala, Uganda, in which we identified three MTBC lineages, of which one, L4.6-Uganda, is clearly derived and hence recent. We quantified TB severity using the Bandim TBscore and examined the interaction between MTBC lineage and human single-nucleotide polymorphisms (SNPs) genome-wide, in two independent cohorts of TB cases (n = 149 and n = 127). We found a significant interaction between an SNP in PPIAP2 and the Uganda lineage (combined p = 4 × 10−8). PPIAP2 is a pseudogene that is highly expressed in immune cells. Pathway and eQTL analyses indicated potential roles between coevolving SNPs and cellular replication and metabolism as well as platelet aggregation and coagulation. This finding provides further evidence that host–pathogen interactions affect clinical presentation differently than host and pathogen genetic variation independently, and that human–MTBC coevolution is likely to explain patterns of disease severity.

scholarly journals Long-term balancing selection in LAD1 maintains a missense trans-species polymorphism in humans, chimpanzees and bonobos

2014 ◽  
Author(s):  
João C. Teixeira ◽  
Cesare de Filippo ◽  
Antje Weihmann ◽  
Juan R. Meneu ◽  
Fernando Racimo ◽  
...  
Keyword(s):  
Balancing Selection ◽  
Phenotypic Diversity ◽  
Intermediate Frequency ◽  
High Genetic Diversity ◽  
Protein Coding ◽  
Missense Change ◽  
Linear Iga Disease ◽  
Filament Protein

Balancing selection maintains advantageous genetic and phenotypic diversity in populations. When selection acts for long evolutionary periods selected polymorphisms may survive species splits and segregate in present-day populations of different species. Here, we investigate the role of long-term balancing selection in the evolution of protein-coding sequences in the Homo-Pan clade. We sequenced the exome of 20 humans, 20 chimpanzees and 20 bonobos and detected eight coding trans-species polymorphisms (trSNPs) that are shared among the three species and have segregated for approximately 14 million years of independent evolution. While the majority of these trSNPs were found in three genes of the MHC cluster, we also uncovered one coding trSNP (rs12088790) in the gene LAD1. All these trSNPs show clustering of sequences by allele rather than by species and also exhibit other signatures of long-term balancing selection, such as segregating at intermediate frequency and lying in a locus with high genetic diversity. Here we focus on the trSNP in LAD1, a gene that encodes for Ladinin-1, a collagenous anchoring filament protein of basement membrane that is responsible for maintaining cohesion at the dermal-epidermal junction; the gene is also an autoantigen responsible for linear IgA disease. This trSNP results in a missense change (Leucine257Proline) and, besides altering the protein sequence, is associated with changes in gene expression of LAD1.

scholarly journals A curated dataset of modern and ancient high-coverage shotgun human genomes

2020 ◽  
Author(s):  
Pierpaolo Maisano Delser ◽  
Eppie R. Jones ◽  
Anahit Hovhannisyan ◽  
Lara Cassidy ◽  
Ron Pinhasi ◽  
...  
Keyword(s):  
Sequence Data ◽  
Whole Genome ◽  
Reference Dataset ◽  
High Coverage ◽  
Sample Distribution ◽  
Human Samples ◽  
Human Genomes ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Computationally Intensive

AbstractOver the last few years, genome-wide data for a large number of ancient human samples have been collected. Whilst datasets of capture SNPs have been collated, high coverage shotgun genomes (which are relatively few but allow certain type of analyses not possible with ascertained captured SNPs) have to be reprocessed by individual groups from raw reads. This task is computationally intensive. Here, we release a dataset including 34 whole-genome sequenced samples, previously published and distributed worldwide, together with the genetic pipeline used to process them. The dataset contains 73,435,604 sites called across 18 ancient and 16 modern individuals and includes sequence data from four previously published ancient samples which we sequenced to higher coverage (10-18x). Such a resource will allow researchers to analyse their new samples with the same genetic pipeline and directly compare them to the reference dataset without re-processing published samples. Moreover, this dataset can be easily expanded to increase the sample distribution both across time and space.

scholarly journals Genome-wide sexually antagonistic variants reveal longstanding constraints on sexual dimorphism in the fruitfly

2017 ◽  
Author(s):  
Filip Ruzicka ◽  
Mark S. Hill ◽  
Tanya M. Pennell ◽  
Ilona Flis ◽  
Fiona C. Ingleby ◽  
...  
Keyword(s):  
Sexual Dimorphism ◽  
Evolutionary Dynamics ◽  
Genome Wide Association Study ◽  
Balancing Selection ◽  
Sexual Antagonism ◽  
Protein Coding ◽  
Genome Wide ◽  
Genomic Location ◽  
Classic Theory ◽  
A Genome

The evolution of sexual dimorphism is constrained by a shared genome, leading to ‘sexual antagonism’ where different alleles at given loci are favoured by selection in males and females. Despite its wide taxonomic incidence, we know little about the identity, genomic location and evolutionary dynamics of antagonistic genetic variants. To address these deficits, we use sex-specific fitness data from 202 fully sequenced hemiclonal D. melanogaster fly lines to perform a genome-wide association study of sexual antagonism. We identify ~230 chromosomal clusters of candidate antagonistic SNPs. In contradiction to classic theory, we find no clear evidence that the X chromosome is a hotspot for sexually antagonistic variation. Characterising antagonistic SNPs functionally, we find a large excess of missense variants but little enrichment in terms of gene function. We also assess the evolutionary persistence of antagonistic variants by examining extant polymorphism in wild D. melanogaster populations. Remarkably, antagonistic variants are associated with multiple signatures of balancing selection across the D. melanogaster distribution range, indicating widespread and evolutionarily persistent (>10,000 years) genomic constraints. Based on our results, we propose that antagonistic variation accumulates due to constraints on the resolution of sexual conflict over protein coding sequences, thus contributing to the long-term maintenance of heritable fitness variation.

scholarly journals Evidence for widespread selection in shaping the genomic landscape during speciation of Populus

2019 ◽  
Author(s):  
Jing Wang ◽  
Nathaniel R. Street ◽  
Eung-Jun Park ◽  
Jianquan Liu ◽  
Pär K. Ingvarsson
Keyword(s):  
Recurrent Selection ◽  
Balancing Selection ◽  
Forest Tree ◽  
Species Variation ◽  
Recombination Rates ◽  
Genome Wide ◽  
Genomic Landscape ◽  
Speciation Continuum ◽  
Whole Genome Resequencing

AbstractIncreasing our understanding of how various evolutionary processes drive the genomic landscape of variation is fundamental to a better understanding of the genomic consequences of speciation. However, the genome-wide patterns of within- and between-species variation have not been fully investigated in most forest tree species despite their global ecological and economic importance. Here, we use whole-genome resequencing data from four Populus species spanning the speciation continuum to reconstruct their demographic histories, investigate patterns of diversity and divergence, infer their genealogical relationships and estimate the extent of ancient introgression across the genome. Our results show substantial variation in these patterns along the genomes although this variation is not randomly distributed but is strongly predicted by the local recombination rates and the density of functional elements. This implies that the interaction between recurrent selection and intrinsic genomic features has dramatically sculpted the genomic landscape over long periods of time. In addition, our findings provide evidence that, apart from background selection, recent positive selection and long-term balancing selection are also crucial components in shaping patterns of genome-wide variation during the speciation process.

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