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

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.

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A Nonsense Variant in Hephaestin Like 1 (HEPHL1) Is Responsible for Congenital Hypotrichosis in Belted Galloway Cattle

Genes ◽

10.3390/genes12050643 ◽

2021 ◽

Vol 12 (5) ◽

pp. 643

Author(s):

Thibaud Kuca ◽

Brandy M. Marron ◽

Joana G. P. Jacinto ◽

Julia M. Paris ◽

Christian Gerspach ◽

...

Keyword(s):

Genome Wide Association Study ◽

Homozygosity Mapping ◽

Mendelian Inheritance ◽

Large Animal Model ◽

Large Animal ◽

Loss Of Function ◽

Protein Coding ◽

Positional Candidate ◽

Genome Wide ◽

A Genome

Genodermatosis such as hair disorders mostly follow a monogenic mode of inheritance. Congenital hypotrichosis (HY) belong to this group of disorders and is characterized by abnormally reduced hair since birth. The purpose of this study was to characterize the clinical phenotype of a breed-specific non-syndromic form of HY in Belted Galloway cattle and to identify the causative genetic variant for this recessive disorder. An affected calf born in Switzerland presented with multiple small to large areas of alopecia on the limbs and on the dorsal part of the head, neck, and back. A genome-wide association study using Swiss and US Belted Galloway cattle encompassing 12 cases and 61 controls revealed an association signal on chromosome 29. Homozygosity mapping in a subset of cases refined the HY locus to a 1.5 Mb critical interval and subsequent Sanger sequencing of protein-coding exons of positional candidate genes revealed a stop gain variant in the HEPHL1 gene that encodes a multi-copper ferroxidase protein so-called hephaestin like 1 (c.1684A>T; p.Lys562*). A perfect concordance between the homozygous presence of this most likely pathogenic loss-of-function variant and the HY phenotype was found. Genotyping of more than 700 purebred Swiss and US Belted Galloway cattle showed the global spread of the mutation. This study provides a molecular test that will permit the avoidance of risk matings by systematic genotyping of relevant breeding animals. This rare recessive HEPHL1-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002230-9913).

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

10.1101/867754 ◽

2019 ◽

Cited By ~ 7

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.

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Population genetics of the coral Acropora millepora: Toward genomic prediction of bleaching

Science ◽

10.1126/science.aba4674 ◽

2020 ◽

Vol 369 (6501) ◽

pp. eaba4674 ◽

Cited By ~ 14

Author(s):

Zachary L. Fuller ◽

Veronique J. L. Mocellin ◽

Luke A. Morris ◽

Neal Cantin ◽

Jihanne Shepherd ◽

...

Keyword(s):

Genome Wide Association Study ◽

Balancing Selection ◽

Conservation Strategies ◽

Genome Sequences ◽

Acropora Millepora ◽

Genome Wide ◽

A Genome ◽

Bleaching Response ◽

In The Wild

Although reef-building corals are declining worldwide, responses to bleaching vary within and across species and are partly heritable. Toward predicting bleaching response from genomic data, we generated a chromosome-scale genome assembly for the coral Acropora millepora. We obtained whole-genome sequences for 237 phenotyped samples collected at 12 reefs along the Great Barrier Reef, among which we inferred 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 conducted a genome-wide association study of visual bleaching score for 213 samples, incorporating the polygenic score derived from it into a predictive model for bleaching in the wild. These results set the stage for genomics-based approaches in conservation strategies.

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Natural variation in insect egg-induced cell death uncovers a role for L-type LECTIN RECEPTOR KINASE-I.1 in Arabidopsis

10.1101/2020.05.29.122846 ◽

2020 ◽

Author(s):

Raphaël Groux ◽

Caroline Gouhier-Darimont ◽

Envel Kerdaffrec ◽

Philippe Reymond

Keyword(s):

Signaling Pathway ◽

Genome Wide Association Study ◽

Balancing Selection ◽

Pieris Brassicae ◽

Receptor Kinase ◽

Large White ◽

Lectin Receptor ◽

Genome Wide ◽

A Genome ◽

Close Homolog

AbstractIn Arabidopsis thaliana, a hypersensitive-like response (HR-like) is triggered underneath the eggs of the large white butterfly Pieris brassicae, and this response is dependent on salicylic acid (SA) accumulation and signaling. Previous reports indicate that the clade I L-type lectin receptor kinase LecRK-I.8 is involved in early steps of egg recognition. A genome-wide association study (GWAS) was used to better characterize the genetic structure of HR-like and discover loci that contribute to this response. We report here the identification of LecRK-I.1, a close homolog of LecRK-I.8, and show that two main haplotypes that explain part of the variation in HR-like segregate amongst natural Arabidopsis accessions. In addition, signatures of balancing selection at this locus suggest that it may be ecologically important. Disruption of LecRK-I.1 resulted in decreased HR-like and SA signaling, indicating that this protein is important for the observed responses. Furthermore, we provide evidence that LecRK-I.1 functions in the same signaling pathway as LecRK-I.8. Altogether, our results show that the response to eggs of P. brassicae is controlled by LecRKs that operate at various steps of the signaling pathway.

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Genome-wide features of introns are evolutionary decoupled among themselves and from genome size throughout Eukarya

10.1101/283549 ◽

2018 ◽

Cited By ~ 4

Author(s):

Irma Lozada-Chávez ◽

Peter F. Stadler ◽

Sonja J. Prohaska

Keyword(s):

Genome Size ◽

Evolutionary Dynamics ◽

Protein Coding ◽

Specific Level ◽

Spliceosomal Introns ◽

Major Mechanism ◽

Genome Wide ◽

A Genome ◽

Eukaryotic Gene ◽

The Impact

AbstractThe impact of spliceosomal introns on genome and organismal evolution remains puzzling. Here, we investigated the correlative associations among genome-wide features of introns from protein-coding genes (e.g., size, density, genome-content, repeats), genome size and multicellular complexity on 461 eukaryotes. Thus, we formally distinguished simple from complex multicellular organisms (CMOs), and developed the program GenomeContent to systematically estimate genomic traits. We performed robust phylogenetic controlled analyses, by taking into account significant uncertainties in the tree of eukaryotes and variation in genome size estimates. We found that changes in the variation of some intron features (such as size and repeat composition) are only weakly, while other features measuring intron abundance (within and across genes) are not, scaling with changes in genome size at the broadest phylogenetic scale. Accordingly, the strength of these associations fluctuates at the lineage-specific level, and changes in the length and abundance of introns within a genome are found to be largely evolving independently throughout Eukarya. Thereby, our findings are in disagreement with previous estimations claiming a concerted evolution between genome size and introns across eukaryotes. We also observe that intron features vary homogeneously (with low repetitive composition) within fungi, plants and stramenophiles; but they vary dramatically (with higher repetitive composition) within holozoans, chlorophytes, alveolates and amoebozoans. We also found that CMOs and their closest ancestral relatives are characterized by high intron-richness, regardless their genome size. These patterns contrast the narrow distribution of exon features found across eukaryotes. Collectively, our findings unveil spliceosomal introns as a dynamically evolving non-coding DNA class and strongly argue against both, a particular intron feature as key determinant of eukaryotic gene architecture, as well as a major mechanism (adaptive or non-adaptive) behind the evolutionary dynamics of introns over a large phylogenetic scale. We hypothesize that intron-richness is a pre-condition to evolve complex multicellularity.

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SVRare: discovering disease-causing structural variants in the 100K Genomes Project

10.1101/2021.10.15.21265069 ◽

2021 ◽

Author(s):

Jing Yu ◽

Anita Szabo ◽

Alistair T Pagnamenta ◽

Ahmed Shalaby ◽

Edoardo Giacopuzzi ◽

...

Keyword(s):

Genome Wide Association Study ◽

Kidney Diseases ◽

Cystic Kidney ◽

Whole Genome Sequencing Data ◽

Structural Variants ◽

Sequencing Data ◽

Protein Coding ◽

Genome Wide ◽

A Genome ◽

Cystic Kidney Diseases

Discovery of disease-causing structural variants (dcSV) from whole genome sequencing data is difficult due to high number of false positives and a lack of efficient way to estimate allele frequency. Here we introduce SVRare, an application that aggregates structural variants (SV) called by other tools, and efficiently annotates rare SVs to aid dcSVs discovery. Applied in the Genomics England (GEL) research environment to data from the 100K Genomes Project, SVRare aggregated 554,060,126 SVs called by Manta and Canvas in all the 71,408 participants in the rare-disease arm. From a pilot study of 4313 families, SVRare identified 36 novel protein-coding disrupting SVs on diagnostic grade genes that may explain proband's phenotype. It is estimated that SVRare can increase SV-based diagnosis yield by at least 4-fold. We also performed a genome-wide association study, and uncovered clusters of dcSVs in genes with known pathogenicity, such as PKD1/2 - cystic kidney diseases and LDLR - familial hypercholesterolaemia.

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