Purifying Selection in Corvids Is Less Efficient on Islands

Abstract Theory predicts that deleterious mutations accumulate more readily in small populations. As a consequence, mutation load is expected to be elevated in species where life-history strategies and geographic or historical contingencies reduce the number of reproducing individuals. Yet, few studies have empirically tested this prediction using genome-wide data in a comparative framework. We collected whole-genome sequencing data for 147 individuals across seven crow species (Corvus spp.). For each species, we estimated the distribution of fitness effects of deleterious mutations and compared it with proxies of the effective population size Ne. Island species with comparatively smaller geographic range sizes had a significantly increased mutation load. These results support the view that small populations have an elevated risk of mutational meltdown, which may contribute to the higher extinction rates observed in island species.

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Recent demography drives changes in linked selection across the maize genome

10.1101/031666 ◽

2015 ◽

Author(s):

Timothy M. Beissinger ◽

Li Wang ◽

Kate Crosby ◽

Arun Durvasula ◽

Matthew B. Hufford ◽

...

Keyword(s):

Population Size ◽

Demographic History ◽

Purifying Selection ◽

Rapid Expansion ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Sequencing Data ◽

Effective Population ◽

The Impact ◽

Linked Selection

AbstractGenetic diversity is shaped by the interaction of drift and selection, but the details of this interaction are not well understood. The impact of genetic drift in a population is largely determined by its demographic history, typically summarized by its long-term effective population size (Ne). Rapidly changing population demographics complicate this relationship, however. To better understand how changing demography impacts selection, we used whole-genome sequencing data to investigate patterns of linked selection in domesticated and wild maize (teosinte). We produce the first whole-genome estimate of the demography of maize domestication, showing that maize was reduced to approximately 5% the population size of teosinte before it experienced rapid expansion post-domestication to population sizes much larger than its ancestor. Evaluation of patterns of nucleotide diversity in and near genes shows little evidence of selection on beneficial amino acid substitutions, and that the domestication bottleneck led to a decline in the efficiency of purifying selection in maize. Young alleles, however, show evidence of much stronger purifying selection in maize, reflecting the much larger effective size of present day populations. Our results demonstrate that recent demographic change — a hallmark of many species including both humans and crops — can have immediate and wide-ranging impacts on diversity that conflict with would-be expectations based on Ne alone.

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Harmful mutation load in the mitochondrial genomes of cattle breeds

BMC Research Notes ◽

10.1186/s13104-021-05664-y ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Sankar Subramanian

Keyword(s):

Population Size ◽

Artificial Selection ◽

Deleterious Mutation ◽

Genetic Diseases ◽

Mitochondrial Genomes ◽

Deleterious Mutations ◽

Founder Population ◽

Mutation Load ◽

Effective Population ◽

Cattle Breeds

Abstract Objective Domestication of wild animals results in a reduction in the effective population size, and this could affect the deleterious mutation load of domesticated breeds. Furthermore, artificial selection will also contribute to the accumulation of deleterious mutations due to the increased rate of inbreeding among these animals. The process of domestication, founder population size, and artificial selection differ between cattle breeds, which could lead to a variation in their deleterious mutation loads. We investigated this using mitochondrial genome data from 364 animals belonging to 18 cattle breeds of the world. Results Our analysis revealed more than a fivefold difference in the deleterious mutation load among cattle breeds. We also observed a negative correlation between the breed age and the proportion of deleterious amino acid-changing polymorphisms. This suggests a proportionally higher deleterious SNPs in young breeds compared to older breeds. Our results highlight the magnitude of difference in the deleterious mutations present in the mitochondrial genomes of various breeds. The results of this study could be useful in predicting the rate of incidence of genetic diseases in different breeds.

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Human-lineage-specific genomic elements are associated with neurodegenerative disease and APOE transcript usage

Nature Communications ◽

10.1038/s41467-021-22262-5 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Zhongbo Chen ◽

◽

David Zhang ◽

Regina H. Reynolds ◽

Emil K. Gustavsson ◽

...

Keyword(s):

Neurological Diseases ◽

Purifying Selection ◽

Whole Genome Sequencing Data ◽

Human Lineage ◽

Sequencing Data ◽

Protein Coding ◽

Potential Association ◽

High Depth ◽

Specific Sequences ◽

Human Specific

AbstractKnowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript to be more abundant in Alzheimer’s disease with more severe tau and amyloid pathological burden. Thus, we demonstrate potential association of human-lineage-specific sequences in brain development and neurological disease.

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Population Genomics of American Mink Using Whole Genome Sequencing Data

Genes ◽

10.3390/genes12020258 ◽

2021 ◽

Vol 12 (2) ◽

pp. 258

Author(s):

Karim Karimi ◽

Duy Ngoc Do ◽

Mehdi Sargolzaei ◽

Younes Miar

Keyword(s):

Population Genomics ◽

Association Studies ◽

American Mink ◽

Population History ◽

Whole Genome Sequencing Data ◽

Whole Genome ◽

Nucleotide Polymorphisms ◽

Sequencing Data ◽

Effective Population ◽

Cross Validation Error

Characterizing the genetic structure and population history can facilitate the development of genomic breeding strategies for the American mink. In this study, we used the whole genome sequences of 100 mink from the Canadian Centre for Fur Animal Research (CCFAR) at the Dalhousie Faculty of Agriculture (Truro, NS, Canada) and Millbank Fur Farm (Rockwood, ON, Canada) to investigate their population structure, genetic diversity and linkage disequilibrium (LD) patterns. Analysis of molecular variance (AMOVA) indicated that the variation among color-types was significant (p < 0.001) and accounted for 18% of the total variation. The admixture analysis revealed that assuming three ancestral populations (K = 3) provided the lowest cross-validation error (0.49). The effective population size (Ne) at five generations ago was estimated to be 99 and 50 for CCFAR and Millbank Fur Farm, respectively. The LD patterns revealed that the average r2 reduced to <0.2 at genomic distances of >20 kb and >100 kb in CCFAR and Millbank Fur Farm suggesting that the density of 120,000 and 24,000 single nucleotide polymorphisms (SNP) would provide the adequate accuracy of genomic evaluation in these populations, respectively. These results indicated that accounting for admixture is critical for designing the SNP panels for genotype-phenotype association studies of American mink.

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Development of additional microsatellite primers for the mangrove tree species Avicennia germinans

10.1101/2020.12.14.422622 ◽

2020 ◽

Author(s):

Hayley Craig ◽

Ilka C Feller ◽

Jennifer K Rowntree

Keyword(s):

Multiplex Pcr ◽

Tree Species ◽

Cost Effective ◽

Avicennia Germinans ◽

Whole Genome Sequencing Data ◽

Microsatellite Primers ◽

Sequencing Data ◽

Effective Population ◽

Mangrove Tree ◽

Primer Sets

Objective: The objective of this study was to develop additional microsatellite primers for the mangrove tree species Avicennia germinans that work in multiplex PCR panels to enable cost effective population analyses of this species at a finer scale. Results: Primer sets were identified from whole genome sequencing data and combined into multiplex PCR panels. Five multiplex reactions containing 20 novel primer sets with trinucleotide repeats were successfully developed. Fifteen of the microsatellite loci were polymorphic in the samples tested, with 1-4 alleles per locus.

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Intra-Species Differences in Population Size shape Life History and Genome Evolution

10.1101/852368 ◽

2019 ◽

Cited By ~ 3

Author(s):

David Willemsen ◽

Rongfeng Cui ◽

Martin Reichard ◽

Dario Riccardo Valenzano

Keyword(s):

Life History ◽

Population Size ◽

Genetic Drift ◽

Sex Chromosome ◽

Purifying Selection ◽

Life History Trait ◽

Deleterious Mutations ◽

Effective Population ◽

Annual Life Cycle ◽

Evolutionary Forces

AbstractThe evolutionary forces shaping life history trait divergence within species are largely unknown. Killifish (oviparous Cyprinodontiformes) evolved an annual life cycle as an exceptional adaptation to life in arid savannah environments characterized by seasonal water availability. The turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate known to science and displays differences in lifespan among wild populations, representing an ideal natural experiment in the evolution and diversification of life history. Here, by combining genome sequencing and population genetics, we investigate the evolutionary forces shaping lifespan among turquoise killifish populations. We generate an improved reference assembly for the turquoise killifish genome, trace the evolutionary origin of the sex chromosome, and identify genes under strong positive and purifying selection, as well as those evolving neutrally. We find that the shortest-lived turquoise killifish populations, which dwell in fragmented and isolated habitats at the outer margin of the geographical range of the species, are characterized by small effective population size and accumulate throughout the genome several small to large-effect deleterious mutations due to genetic drift. The genes most affected by drift in the shortest-lived turquoise killifish populations are involved in the WNT signalling pathway, neurodegenerative disorders, cancer and the mTOR pathway. As the populations under stronger genetic drift are the shortest-lived ones, we propose that limited population size due to habitat fragmentation and repeated population bottlenecks, by causing the genome-wide accumulation of deleterious mutations, cumulatively contribute to the short adult lifespan in turquoise killifish populations.

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Harmful Mutation Load in the Mitochondrial Genomes of Cattle Breeds

10.21203/rs.3.rs-362860/v1 ◽

2021 ◽

Author(s):

Sankar Subramanian

Keyword(s):

Amino Acid ◽

Population Size ◽

Artificial Selection ◽

Deleterious Mutation ◽

Mitochondrial Genomes ◽

Deleterious Mutations ◽

Founder Population ◽

Mutation Load ◽

Effective Population ◽

Cattle Breeds

Abstract ObjectiveDomestication of wild animals results in a reduction in the effective population size and this could affect the deleterious mutation load of domesticated breeds. Furthermore, artificial selection will also contribute to accumulation deleterious mutations due to the increased rate of inbreeding among these animals. The process of domestication, founder population size, and artificial selection differ between cattle breeds, which could lead to a variation in their deleterious mutation loads. We investigated this using mitochondrial genome data from 252 animals belonging to 15 cattle breeds of the world. ResultsOur analysis revealed more than fivefold difference in the deleterious mutation load among cattle breeds. We also observed a negative correlation between the neutral heterozygosity and the ratio of amino acid changing diversity to silent diversity. This suggests a proportionally higher amino acid changing variants in breeds with low diversity. Our results highlight the magnitude of difference in the deleterious mutations present in the mitochondrial genomes of various breeds. The results of this study could be useful in predicting the rate of incidence of genetic diseases in different breeds.

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Relaxation of purifying selection suggests low effective population size in eusocial Hymenoptera and solitary pollinating bees

10.1101/2020.04.14.038893 ◽

2020 ◽

Author(s):

Arthur Weyna ◽

Jonathan Romiguier

Keyword(s):

Population Size ◽

Effective Population Size ◽

Ecosystem Engineer ◽

Relative Rate ◽

Population Decline ◽

Purifying Selection ◽

Life History Strategies ◽

Effective Population ◽

Social Bees ◽

Pollinator Species

ABSTRACTWith one of the highest number of parasite, eusocial and pollinator species among all insect orders, Hymenoptera features a great diversity of specific lifestyles. At the population genetic level, such life-history strategies are expected to decrease effective population size and efficiency of purifying selection. In this study, we tested this hypothesis by estimating the relative rate of non-synonymous substitution in 169 species to investigate the variation in natural selection efficiency throughout the hymenopteran tree of life. We found no effect of parasitism or body size, but show that relaxed selection is associated with eusociality, suggesting that the division of reproductive labour decreases effective population size in ants, bees and wasps. Unexpectedly, the effect of eusociality is marginal compared to a striking and widespread relaxation of selection in both social and non social bees, which indicates that these keystone pollinator species generally feature low effective population sizes. This widespread pattern suggests specific constraints in pollinating bees potentially linked to limited resource and high parental investment. The particularly high load of deleterious mutations we report in the genome of these crucial ecosystem engineer species also raises new concerns about their ongoing population decline.

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Human-lineage-specific genomic elements: relevance to neurodegenerative disease and APOE transcript usage

10.1101/2020.04.17.046441 ◽

2020 ◽

Author(s):

Zhongbo Chen ◽

David Zhang ◽

Regina H. Reynolds ◽

Emil K. Gustavsson ◽

Sonia García Ruiz ◽

...

Keyword(s):

Neurological Diseases ◽

Purifying Selection ◽

Whole Genome Sequencing Data ◽

Human Lineage ◽

Sequencing Data ◽

Protein Coding ◽

Genomic Features ◽

High Depth ◽

Specific Sequences ◽

Human Specific

ABSTRACTKnowledge of genomic features specific to the human lineage may provide insights into brain-related diseases. We leverage high-depth whole genome sequencing data to generate a combined annotation identifying regions simultaneously depleted for genetic variation (constrained regions) and poorly conserved across primates. We propose that these constrained, non-conserved regions (CNCRs) have been subject to human-specific purifying selection and are enriched for brain-specific elements. We find that CNCRs are depleted from protein-coding genes but enriched within lncRNAs. We demonstrate that per-SNP heritability of a range of brain-relevant phenotypes are enriched within CNCRs. We find that genes implicated in neurological diseases have high CNCR density, including APOE, highlighting an unannotated intron-3 retention event. Using human brain RNA-sequencing data, we show the intron-3-retaining transcript/s to be more abundant in Alzheimer’s disease with more severe tau and amyloid pathological burden. Thus, we demonstrate the importance of human-lineage-specific sequences in brain development and neurological disease. We release our annotation through vizER (https://snca.atica.um.es/browser/app/vizER).

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The Effects of Deleterious Mutations on Linked, Neutral Variation in Small Populations

Genetics ◽

10.1093/genetics/153.1.475 ◽

1999 ◽

Vol 153 (1) ◽

pp. 475-483 ◽

Cited By ~ 2

Author(s):

Snæbjörn Pálsson ◽

Pekka Pamilo

Keyword(s):

Small Populations ◽

Background Selection ◽

Deleterious Mutations ◽

Selection Coefficient ◽

Effective Population ◽

Strong Reduction ◽

Tight Linkage ◽

Neutral Marker ◽

Population Sizes ◽

Clear Increase

Abstract The effects of recessive, deleterious mutations on genetic variation at linked neutral loci can be heterozygosity-decreasing because of reduced effective population sizes or heterozygosity-increasing because of associative overdominance. Here we examine the balance between these effects by simulating individual diploid genotypes in small panmictic populations. The haploid genome consists of one linkage group with 1000 loci that can have deleterious mutations and a neutral marker. Combinations of the following parameters are studied: gametic mutation rate to harmful alleles (U), population size (N), recombination rate (r), selection coefficient (s), and dominance (h). Tight linkage (r ≤ 10–4) gives significant associative effects, leading either to strong reduction of heterozygosity when the product Nhs is large or to a clear increase when the product Nhs is small, the boundary between these effects being 1 < Nhs < 4 in our simulations. Associative overdominance can lead to heterozygosities that are larger than predicted by the background selection models and even larger than the neutral expectation.

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