| 1. |
- 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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| 2. |
- Baruch, Zdravko, et al.
(författare)
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Functional acclimation across microgeographic scales in Dodonaea viscosa
- 2018
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Ingår i: AoB Plants. - : Oxford University Press (OUP). - 2041-2851. ; 10:3
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Tidskriftsartikel (refereegranskat)abstract
- Intraspecific plant functional trait variation provides mechanistic insight into persistence and can infer population adaptive capacity. However, most studies explore intraspecific trait variation in systems where geographic and environmental distances co-vary. Such a design reduces the certainty of trait-environment associations, and it is imperative for studies that make trait-environment associations be conducted in systems where environmental distance varies independently of geographic distance. Here we explored trait variation in such a system, and aimed to: (i) quantify trait variation of parent and offspring generations, and associate this variation to parental environments; (ii) determine the traits which best explain population differences; (iii) compare parent and offspring trait-trait relationships. We characterized 15 plant functional traits in eight populations of a shrub with a maximum separation ca. 100 km. Populations differed markedly in aridity and elevation, and environmental distance varied independently of geographic distance. We measured traits in parent populations collected in the field, as well as their offspring reared in greenhouse conditions. Parent traits regularly associated with their environment. These associations were largely lost in the offspring generation, indicating considerable phenotypic plasticity. An ordination of parent traits showed clear structure with strong influence of leaf area, specific leaf area, stomatal traits, isotope delta C-13 and delta N-15 ratios, and N-area, whereas the offspring ordination was less structured. Parent trait-trait correlations were in line with expectations from the leaf economic spectrum. We show considerable trait plasticity in the woody shrub over microgeographic scales (<100 km), indicating it has the adaptive potential within a generation to functionally acclimate to a range of abiotic conditions. Since our study shrub is commonly used for restoration in southern Australia and local populations do not show strong genetic differentiation in functional traits, the potential risks of transferring seed across the broad environmental conditions are not likely to be a significant issue.
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| 3. |
- Christmas, Matthew, et al.
(författare)
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Evolutionary constraint and innovation across hundreds of placental mammals
- 2023
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 380:6643
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Tidskriftsartikel (refereegranskat)abstract
- Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (similar to 10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth's vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
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| 4. |
- Christmas, Matthew J, et al.
(författare)
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Chromosomal inversions associated with environmental adaptation in honeybees
- 2019
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Ingår i: Molecular Ecology. - : WILEY. - 0962-1083 .- 1365-294X. ; 28:6, s. 1358-1374
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Tidskriftsartikel (refereegranskat)abstract
- Chromosomal inversions can facilitate local adaptation in the presence of gene flow by suppressing recombination between well-adapted native haplotypes and poorly adapted migrant haplotypes. East African mountain populations of the honeybee Apis mellifera are highly divergent from neighbouring lowland populations at two extended regions in the genome, despite high similarity in the rest of the genome, suggesting that these genomic regions harbour inversions governing local adaptation. Here, we utilize a new highly contiguous assembly of the honeybee genome to characterize these regions. Using whole-genome sequencing data from 55 highland and lowland bees, we find that the highland haplotypes at both regions are present at high frequencies in three independent highland populations but extremely rare elsewhere. The boundaries of both divergent regions are characterized by regions of high homology with each other positioned in opposite orientations and contain highly repetitive, long inverted repeats with homology to transposable elements. These regions are likely to represent inversion breakpoints that participate in nonallelic homologous recombination. Using long-read data, we confirm that the lowland samples are contiguous across breakpoint regions. We do not find evidence for disruption of functional sequence by these breakpoints, which suggests that the inversions are likely maintained due to their allelic content conferring local adaptation in highland environments. Finally, we identify a third divergent genomic region, which contains highly divergent segregating haplotypes that also may contain inversion variants under selection. The results add to a growing body of evidence indicating the importance of chromosomal inversions in local adaptation.
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| 5. |
- Sanchez-Donoso, Ines, et al.
(författare)
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Massive genome inversion drives coexistence of divergent morphs in common quails
- 2022
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Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 32:2, s. 462-
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Tidskriftsartikel (refereegranskat)abstract
- The presence of population-specific phenotypes often reflects local adaptation or barriers to gene flow. The co-occurrence of phenotypic polymorphisms that are restricted within the range of a highly mobile species is more difficult to explain. An example of such polymorphisms is in the common quail Coturnix coturnix, a small migratory bird that moves widely during the breeding season in search of new mating opportunities, following ephemeral habitats,(1,2) and whose females may lay successive clutches at different locations while migrating.(3) In spite of this vagility, previous studies reported a higher frequency of heavier males with darker throat coloration in the southwest of the distribution (I. Jimenez-Blasco et al., 2015, Int. Union Game Biol., conference). We used population genomics and cytogenetics to explore the basis of this polymorphism and discovered a large inversion in the genome of the common quail. This inversion extends 115 Mbp in length and encompasses more than 7,000 genes (about 12% of the genome), producing two very different forms. Birds with the inversion are larger, have darker throat coloration and rounder wings, are inferred to have poorer flight efficiency, and are geographically restricted despite the high mobility of the species. Stable isotope analyses confirmed that birds carrying the inversion have shorter migratory distances or do not migrate. However, we found no evidence of pre- or post-zygotic isolation, indicating the two forms commonly interbreed and that the polymorphism remains locally restricted because of the effect on behavior. This illustrates a genomic mechanism underlying maintenance of geographically structured polymorphisms despite interbreeding with a lineage with high mobility.
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| 6. |
- Blyth, Colette, et al.
(författare)
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Genomic, Habitat, and Leaf Shape Analyses Reveal a Possible Cryptic Species and Vulnerability to Climate Change in a Threatened Daisy
- 2021
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Ingår i: Life. - : MDPI. - 2075-1729. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- Olearia pannosa is a plant species listed as vulnerable in Australia. Two subspecies are currently recognised (O. pannosa subsp. pannosa (silver daisy) and O. pannosa subsp. cardiophylla (velvet daisy)), which have overlapping ranges but distinct leaf shape. Remnant populations face threats from habitat fragmentation and climate change. We analysed range-wide genomic data and leaf shape variation to assess population diversity and divergence and to inform conservation management strategies. We detected three distinct genetic groupings and a likely cryptic species. Samples identified as O. pannosa subsp. cardiophylla from the Flinders Ranges in South Australia were genetically distinct from all other samples and likely form a separate, range-restricted species. Remaining samples formed two genetic clusters, which aligned with leaf shape differences but not fully with current subspecies classifications. Levels of genetic diversity and inbreeding differed between the three genetic groups, suggesting each requires a separate management strategy. Additionally, we tested for associations between genetic and environmental variation and carried out habitat suitability modelling for O. pannosa subsp. pannosa populations. We found mean annual maximum temperature explained a significant proportion of genomic variance. Habitat suitability modelling identified mean summer maximum temperature, precipitation seasonality and mean annual rainfall as constraints on the distribution of O. pannosa subsp. pannosa, highlighting increasing aridity as a threat for populations located near suitability thresholds. Our results suggest maximum temperature is an important agent of selection on O. pannosa subsp. pannosa and should be considered in conservation strategies. We recommend taxonomic revision of O. pannosa and provide conservation management recommendations.
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| 7. |
- Blyth, Colette, et al.
(författare)
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Increased Genetic Diversity via Gene Flow Provides Hope for Acacia whibleyana, an Endangered Wattle Facing Extinction
- 2020
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Ingår i: Diversity. - : MDPI AG. - 1424-2818. ; 12:8
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Tidskriftsartikel (refereegranskat)abstract
- In this paper we apply a conservation genomics approach to make evidence-based management recommendations forAcacia whibleyana,an endangered shrub endemic to Eyre Peninsula, South Australia. We used population genomic analysis to assess genetic connectivity, diversity, and historical inbreeding across all known stands of the species sampling remnant stands, revegetated stands of unknown origin, and a post-fire seedling cohort. Our results indicate a degree of historical connectivity across the landscape, but habitat loss and/or pollinator community disruption are potential causes of strong genetic structure across the remnant stands. Remnant stands had low genetic diversity and showed evidence of historical inbreeding, but only low levels of intra-stand relatedness indicating that risks of contemporary inbreeding are low. Analysis of a post-fire first generation cohort of seedlings showed they likely resulted from intra-stand matings, resulting in reduced genetic diversity compared to the parents. However, admixed seedlings in this cohort showed an increase in heterozygosity relative to likely sources and the non-admixed seedlings of the same stand. Assisted inter-stand gene flow may prove an effective management strategy to boost heterozygosity and corresponding increases in adapting capacity in this endangered species.
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| 8. |
- Christmas, Matthew, et al.
(författare)
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Measuring genome-wide genetic variation to reassess subspecies classifications in Dodonaea viscosa (Sapindaceae)
- 2018
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Ingår i: Australian Journal of Botany. - : CSIRO PUBLISHING. - 0067-1924 .- 1444-9862. ; 66:4, s. 287-297
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Tidskriftsartikel (refereegranskat)abstract
- Subspecies are traditionally defined on the basis of geographic discontinuities in phenotypic traits, and their circumscription is useful to distinguish morphologically differentiated populations. However, the robustness of morphology-based subspecies classifications in the genomics era is coming under increasing scrutiny, and phylogenies inferred from molecular data may not match with morphological approaches. The division of the shrub Dodonaea viscosa into seven subspecies within Australia has been based mainly on variation in leaf shape, which is a notably variable phenotypic character in this species. So as to assess the alignment between genetic variation and subspecies assignment, we genotyped 67 D. viscosa plants, including representatives from each of the seven subspecies, for 941 single nucleotide polymorphisms. Weused network-and Bayesian-based methods to assess genetic relatedness between sampled individuals. Structure analysis identified two genetic clusters, with a further substructure being identified within one of the clusters. Genetic clusters partially aligned with subspecies classifications, particularly for the three most morphologically distinct subspecies (ssp. mucronata, ssp. viscosa and ssp. burmanniana). Subspecies inhabiting the arid zone (ssp. mucronata and ssp. angustissima) exhibited the most distinct genetic clustering. For subspecies inhabiting more temperate regions of its range (ssp. angustifolia, ssp. cuneata and ssp. spatulata), genetic groups did not correspond well with subspecies classifications, but rather were better explained by the geographic origin of individuals. We suggest that the current subspecific classification of the hopbush does not accurately reflect the evolutionary history of this species, and recommend that phenotypic variation be reassessed in light of the genetic structure we describe here. The roles of environmental change, selection and geographic isolation are discussed in an attempt to explain the contemporary distribution of genetic variation in D. viscosa in Australia.
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| 9. |
- Jhavar, Sameer, et al.
(författare)
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Integration of ERG gene mapping and gene-expression profiling identifies distinct categories of human prostate cancer
- 2009
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Ingår i: BJU International. - 1464-4096. ; 103:9, s. 1256-1269
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To integrate the mapping of ERG alterations with the collection of expression microarray (EMA) data, as previous EMA analyses have failed to consider the genetic heterogeneity and complex patterns of ERG alteration frequently found in cancerous prostates. MATERIALS AND METHODS We determined genome-wide expression levels with GeneChip Human Exon 1.0 ST arrays (Affymetrix, Santa Clara, CA, USA) using RNA prepared from 35 specimens of prostate cancer from 28 prostates. RESULTS The expression profiles showed clustering, in unsupervised hierarchical analyses, into two distinct prostate cancer categories, with one group strongly associated with indicators of poor clinical outcome. The two categories are not tightly linked to ERG status. By analysis of the data we identified a subgroup of cancers lacking ERG rearrangements that showed an outlier pattern of SPINK1 mRNA expression. There was a major distinction between ERG rearranged and non-rearranged cancers that involves the levels of expression of genes linked to exposure to beta-oestradiol, and to retinoic acid. CONCLUSIONS Expression profiling of prostate cancer samples containing single patterns of ERG alterations can provide novel insights into the mechanism of prostate cancer development, and support the view that factors other than ERG status are the major determinants of poor clinical outcome.
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| 10. |
- Kireta, Dona, et al.
(författare)
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Disentangling the evolutionary history of three related shrub species using genome-wide molecular markers
- 2019
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Ingår i: Conservation Genetics. - : Springer Science and Business Media LLC. - 1566-0621 .- 1572-9737. ; 20:5, s. 1101-1112
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Tidskriftsartikel (refereegranskat)abstract
- Understanding population genetic structure provides insight into historic population connectivity, and is largely driven by migration, population size, and species life history. During the last glacial maximum, sea levels around the biogeographically interesting, but poorly studied, South Australian coastal plains and geosyncline were thought to be sufficiently low that three prominent peninsulas (Fleurieu, Yorke, Eyre) and a large offshore island (Kangaroo Island) formed a continuous landmass. However, the degree to which population genetic structure in this region has been shaped by biogeography remains largely untested. Here, we use genome-wide SNP data from three Goodenia shrub species with contrasting growth forms to assess how historical and contemporary processes have shaped population genetic structure. These species occur commonly throughout South Australia and are used extensively in revegetation. The two woody species (Goodenia varia, G. ovata) displayed low genetic differentiation across the southern parts of the peninsulas and island, reflecting historical landscape connectivity. The third more-herbaceous species (G. amplexans) displayed higher genetic structure across the land features, reflecting contemporary disconnectivity. Kangaroo Island and the southern Flinders Ranges had relatively high genetic diversity, providing further evidence that they were important putative Pleistocene refugia. We demonstrate that historic changes in landscape and possible migration to and from refugia, have shaped the population genetic structure in these closely related shrubs, which may have been influenced by contemporary factors and small population sizes. We highlight the importance of using multi-species designs when studying historical population connectivity in understudied regions of the world.
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