| 1. |
- Gao, Hong, et al.
(författare)
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The landscape of tolerated genetic variation in humans and primates
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648
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Tidskriftsartikel (refereegranskat)abstract
- Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.
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| 2. |
- Hoban, Sean, et al.
(författare)
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Global Commitments to Conserving and Monitoring Genetic Diversity Are Now Necessary and Feasible
- 2021
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Ingår i: BioScience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 71:9, s. 964-976
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Tidskriftsartikel (refereegranskat)abstract
- Global conservation policy and action have largely neglected protecting and monitoring genetic diversity-one of the three main pillars of biodiversity. Genetic diversity (diversity within species) underlies species' adaptation and survival, ecosystem resilience, and societal innovation. The low priority given to genetic diversity has largely been due to knowledge gaps in key areas, including the importance of genetic diversity and the trends in genetic diversity change; the perceived high expense and low availability and the scattered nature of genetic data; and complicated concepts and information that are inaccessible to policymakers. However, numerous recent advances in knowledge, technology, databases, practice, and capacity have now set the stage for better integration of genetic diversity in policy instruments and conservation efforts. We review these developments and explore how they can support improved consideration of genetic diversity in global conservation policy commitments and enable countries to monitor, report on, and take action to maintain or restore genetic diversity.
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| 3. |
- Jensen, Evelyn L., et al.
(författare)
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Ancient and historical DNA in conservation policy
- 2022
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Ingår i: Trends in Ecology & Evolution. - : Elsevier. - 0169-5347 .- 1872-8383. ; 37:5, s. 420-429
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Forskningsöversikt (refereegranskat)abstract
- Although genetic diversity has been recognized as a key component of biodiversity since the first Convention on Biological Diversity (CBD) in 1993, it has rarely been included in conservation policies and regulations. Even less appreciated is the role that ancient and historical DNA (aDNA and hDNA, respectively) could play in unlocking the temporal dimension of genetic diversity, allowing key conservation issues to be resolved, including setting baselines for intraspecies genetic diversity, estimating changes in effective population size (N-e), and identifying the genealogical continuity of populations. Here, we discuss how genetic information from ancient and historical specimens can play a central role in preserving biodiversity and highlight specific conservation policies that could incorporate such data to help countries meet their CBD obligations.
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| 4. |
- Kuderna, Lukas F. K., et al.
(författare)
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A global catalog of whole-genome diversity from 233 primate species
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6648, s. 906-913
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Tidskriftsartikel (refereegranskat)abstract
- The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage wholegenome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.
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| 5. |
- Kuderna, Lukas F. K., et al.
(författare)
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Identification of constrained sequence elements across 239 primate genomes
- 2024
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Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 625:7996, s. 735-742
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Tidskriftsartikel (refereegranskat)abstract
- Noncoding DNA is central to our understanding of human gene regulation and complex diseases1,2, and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome3,4,5,6,7,8,9. Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA10, the relatively short timescales separating primate species11, and the previously limited availability of whole-genome sequences12. Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals.
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| 6. |
- O'Brien, David, et al.
(författare)
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Bringing together approaches to reporting on within species genetic diversity
- 2022
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Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 59:9, s. 2227-2233
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Tidskriftsartikel (refereegranskat)abstract
- Genetic diversity is one of the three main levels of biodiversity recognised in the Convention on Biological Diversity (CBD). Fundamental for species adaptation to environmental change, genetic diversity is nonetheless under-reported within global and national indicators. When it is reported, the focus is often narrow and confined to domesticated or other commercial species.Several approaches have recently been developed to address this shortfall in reporting on genetic diversity of wild species. While multiplicity of approaches is helpful in any development process, it can also lead to confusion among policy makers and heighten a perception that conservation genetics is too abstract to be of use to organisations and governments.As the developers of five of the different approaches, we have come together to explain how various approaches relate to each other and propose a scorecard, as a unifying reporting mechanism for genetic diversity.Policy implications. We believe the proposed combined approach captures the strengths of its components and is practical for all nations and subnational governments. It is scalable and can be used to evaluate species conservation projects as well as genetic conservation projects.
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| 7. |
- Pearman, Peter B., et al.
(författare)
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Monitoring of species' genetic diversity in Europe varies greatly and overlooks potential climate change impacts
- 2024
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Ingår i: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 8:2, s. 267-281
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Tidskriftsartikel (refereegranskat)abstract
- Genetic monitoring of populations currently attracts interest in the context of the Convention on Biological Diversity but needs long-term planning and investments. However, genetic diversity has been largely neglected in biodiversity monitoring, and when addressed, it is treated separately, detached from other conservation issues, such as habitat alteration due to climate change. We report an accounting of efforts to monitor population genetic diversity in Europe (genetic monitoring effort, GME), the evaluation of which can help guide future capacity building and collaboration towards areas most in need of expanded monitoring. Overlaying GME with areas where the ranges of selected species of conservation interest approach current and future climate niche limits helps identify whether GME coincides with anticipated climate change effects on biodiversity. Our analysis suggests that country area, financial resources and conservation policy influence GME, high values of which only partially match species' joint patterns of limits to suitable climatic conditions. Populations at trailing climatic niche margins probably hold genetic diversity that is important for adaptation to changing climate. Our results illuminate the need in Europe for expanded investment in genetic monitoring across climate gradients occupied by focal species, a need arguably greatest in southeastern European countries. This need could be met in part by expanding the European Union's Birds and Habitats Directives to fully address the conservation and monitoring of genetic diversity. Comparing data on genetic monitoring efforts across Europe with the distributions of areas at species' climatic niche margins, the authors show that monitoring efforts should be expanded to populations at trailing niche margins to include genetic variation that may prove important for adaptation to ongoing climate warming.
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| 8. |
- Pečnerová, Patrícia, et al.
(författare)
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Population genomics of the muskox' resilience in the near absence of genetic variation
- 2024
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Ingår i: Molecular Ecology. - 0962-1083 .- 1365-294X. ; 33:2
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Tidskriftsartikel (refereegranskat)abstract
- Genomic studies of species threatened by extinction are providing crucial information about evolutionary mechanisms and genetic consequences of population declines and bottlenecks. However, to understand how species avoid the extinction vortex, insights can be drawn by studying species that thrive despite past declines. Here, we studied the population genomics of the muskox (Ovibos moschatus), an Ice Age relict that was at the brink of extinction for thousands of years at the end of the Pleistocene yet appears to be thriving today. We analysed 108 whole genomes, including present-day individuals representing the current native range of both muskox subspecies, the white-faced and the barren-ground muskox (O. moschatus wardi and O. moschatus moschatus) and a ~21,000-year-old ancient individual from Siberia. We found that the muskox' demographic history was profoundly shaped by past climate changes and post-glacial re-colonizations. In particular, the white-faced muskox has the lowest genome-wide heterozygosity recorded in an ungulate. Yet, there is no evidence of inbreeding depression in native muskox populations. We hypothesize that this can be explained by the effect of long-term gradual population declines that allowed for purging of strongly deleterious mutations. This study provides insights into how species with a history of population bottlenecks, small population sizes and low genetic diversity survive against all odds.
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