| 1. |
- Clark, Andrew G., et al.
(författare)
-
Evolution of genes and genomes on the Drosophila phylogeny
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
-
Tidskriftsartikel (refereegranskat)abstract
- Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.
|
|
| 2. |
- Seehausen, Ole, et al.
(författare)
-
Genomics and the origin of species
- 2014
-
Ingår i: Nature reviews genetics. - : Springer Science and Business Media LLC. - 1471-0056 .- 1471-0064. ; 15:3, s. 176-192
-
Forskningsöversikt (refereegranskat)abstract
- Speciation is a fundamental evolutionary process, the knowledge of which is crucial for understanding the origins of biodiversity. Genomic approaches are an increasingly important aspect of this research field. We review current understanding of genome-wide effects of accumulating reproductive isolation and of genomic properties that influence the process of speciation. Building on this work, we identify emergent trends and gaps in our understanding, propose new approaches to more fully integrate genomics into speciation research, translate speciation theory into hypotheses that are testable using genomic tools and provide an integrative definition of the field of speciation genomics.
|
|
| 3. |
- Barlind, Jonas G, et al.
(författare)
-
Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687)
- 2012
-
Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:23, s. 10610-10629
-
Tidskriftsartikel (refereegranskat)abstract
- A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.
|
|
| 4. |
- Duvaux, L., et al.
(författare)
-
Dynamics of copy number variation in host races of the pea aphid
- 2015
-
Ingår i: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 32:1, s. 63-80
-
Tidskriftsartikel (refereegranskat)abstract
- Copy number variation (CNV) makes a major contribution to overall genetic variation and is suspected to play an important role in adaptation. However, aside from a few model species, the extent of CNV in natural populations has seldom been investigated. Here, we report on CNV in the pea aphid Acyrthosiphon pisum, a powerful system for studying the genetic architecture of host-plant adaptation and speciation thanks to multiple host races forming a continuum of genetic divergence. Recent studies have highlighted the potential importance of chemosensory genes, including the gustatory and olfactory receptor gene families (Gr and Or, respectively), in the process of host race formation. We used targeted resequencing to achieve a very high depth of coverage, and thereby revealed the extent of CNV of 434 genes, including 150 chemosensory genes, in 104 individuals distributed across eight host races of the pea aphid. We found that CNV was widespread in our global sample, with a significantly higher occurrence in multigene families, especially in Ors. We also observed a decrease in the gene probability of being completely duplicated or deleted (CDD) with increase in coding sequence length. Genes with CDD variants were usually more polymorphic for copy number, especially in the P450 gene family where toxin resistance may be related to gene dosage. We found that Gr were overrepresented among genes discriminating host races, as were CDD genes and pseudogenes. Our observations shed new light on CNV dynamics and are consistent with CNV playing a role in both local adaptation and speciation.
|
|
| 5. |
- Fountain, Toby, et al.
(författare)
-
A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius
- 2016
-
Ingår i: G3-Genes Genomes Genetics. - : Oxford University Press (OUP). - 2160-1836. ; 6:12, s. 4059-4066
-
Tidskriftsartikel (refereegranskat)abstract
- The rapid evolution of insecticide resistance remains one of the biggest challenges in the control of medically and economically important pests. Insects have evolved a diverse range of mechanisms to reduce the efficacy of the commonly used classes of insecticides, and finding the genetic basis of resistance is a major aid to management. In a previously unstudied population, we performed an F-2 resistance mapping cross for the common bed bug, Cimex lectularius, for which insecticide resistance is increasingly widespread. Using 334 SNP markers obtained through RAD-sequencing, we constructed the first linkage map for the species, consisting of 14 putative linkage groups (LG), with a length of 407 cM and an average marker spacing of 1.3 cM. The linkage map was used to reassemble the recently published reference genome, facilitating refinement and validation of the current genome assembly. We detected a major QTL on LG12 associated with insecticide resistance, occurring in close proximity (1.2 Mb) to a carboxylesterase encoding candidate gene for pyrethroid resistance. This provides another example of this candidate gene playing a major role in determining survival in a bed bug population following pesticide resistance evolution. The recent availability of the bed bug genome, complete with a full list of potential candidate genes related to insecticide resistance, in addition to the linkage map generated here, provides an excellent resource for future research on the development and spread of insecticide resistance in this resurging pest species.
|
|
| 6. |
- Fountain, T., et al.
(författare)
-
Outbreeding effects in an inbreeding insect, Cimex lectularius
- 2015
-
Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 5:2, s. 409-418
-
Tidskriftsartikel (refereegranskat)abstract
- In some species, populations with few founding individuals can be resilient to extreme inbreeding. Inbreeding seems to be the norm in the common bed bug, Cimex lectularius, a flightless insect that, nevertheless, can reach large deme sizes and persist successfully. However, bed bugs can also be dispersed passively by humans, exposing inbred populations to gene flow from genetically distant populations. The introduction of genetic variation through this outbreeding could lead to increased fitness (heterosis) or be costly by causing a loss of local adaptation or exposing genetic incompatibility between populations (outbreeding depression). Here, we addressed how inbreeding within demes and outbreeding between distant populations impact fitness over two generations in this re-emerging public health pest. We compared fitness traits of families that were inbred (mimicking reproduction following a founder event) or outbred (mimicking reproduction following a gene flow event). We found that outbreeding led to increased starvation resistance compared to inbred families, but this benefit was lost after two generations of outbreeding. No other fitness benefits of outbreeding were observed in either generation, including no differences in fecundity between the two treatments. Resilience to inbreeding is likely to result from the history of small founder events in the bed bug. Outbreeding benefits may only be detectable under stress and when heterozygosity is maximized without disruption of coadaptation. We discuss the consequences of these results both in terms of inbreeding and outbreeding in populations with genetic and spatial structuring, as well as for the recent resurgence of bed bug populations.
|
|
| 7. |
- Hearn, K. E., et al.
(författare)
-
Differing associations between sex determination and sex-linked inversions in two ecotypes of Littorina saxatilis
- 2022
-
Ingår i: Evolution Letters. - : Oxford University Press (OUP). - 2056-3744. ; 6:5, s. 358-74
-
Tidskriftsartikel (refereegranskat)abstract
- Sexual antagonism is a common hypothesis for driving the evolution of sex chromosomes, whereby recombination suppression is favored between sexually antagonistic loci and the sex-determining locus to maintain beneficial combinations of alleles. This results in the formation of a sex-determining region. Chromosomal inversions may contribute to recombination suppression but their precise role in sex chromosome evolution remains unclear. Because local adaptation is frequently facilitated through the suppression of recombination between adaptive loci by chromosomal inversions, there is potential for inversions that cover sex-determining regions to be involved in local adaptation as well, particularly if habitat variation creates environment-dependent sexual antagonism. With these processes in mind, we investigated sex determination in a well-studied example of local adaptation within a species: the intertidal snail, Littorina saxatilis. Using SNP data from a Swedish hybrid zone, we find novel evidence for a female-heterogametic sex determination system that is restricted to one ecotype. Our results suggest that four putative chromosomal inversions, two previously described and two newly discovered, span the putative sex chromosome pair. We determine their differing associations with sex, which suggest distinct strata of differing ages. The same inversions are found in the second ecotype but do not show any sex association. The striking disparity in inversion-sex associations between ecotypes that are connected by gene flow across a habitat transition that is just a few meters wide indicates a difference in selective regime that has produced a distinct barrier to the spread of the newly discovered sex-determining region between ecotypes. Such sex chromosome-environment interactions have not previously been uncovered in L. saxatilis and are known in few other organisms. A combination of both sex-specific selection and divergent natural selection is required to explain these highly unusual patterns.
|
|
| 8. |
- Kawakami, Takeshi, et al.
(författare)
-
Hybrid Zones
- 2012
-
Ingår i: eLS. - : John Wiley & Sons. - 9780470015902
-
Bokkapitel (refereegranskat)
|
|
| 9. |
- Kulmuni, J., et al.
(författare)
-
Instability of natural selection at candidate barrier loci underlying speciation in wood ants
- 2020
-
Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 29:20, s. 3988-3999
-
Tidskriftsartikel (refereegranskat)abstract
- Speciation underlies the generation of novel biodiversity. Yet, there is much to learn about how natural selection shapes genomes during speciation. Selection is assumed to act against gene flow at barrier loci, promoting reproductive isolation. However, evidence for gene flow and selection is often indirect and we know very little about the temporal stability of barrier loci. Here we utilize haplodiploidy to identify candidate male barrier loci in hybrids between two wood ant species. As ant males are haploid, they are expected to reveal recessive barrier loci, which can be masked in diploid females if heterozygous. We then test for barrier stability in a sample collected 10 years later and use survival analysis to provide a direct measure of natural selection acting on candidate male barrier loci. We find multiple candidate male barrier loci scattered throughout the genome. Surprisingly, a proportion of them are not stable after 10 years, natural selection apparently switching from acting against to favouring introgression in the later sample. Instability of the barrier effect and natural selection for introgressed alleles could be due to environment-dependent selection, emphasizing the need to consider temporal variation in the strength of natural selection and the stability of the barrier effect at putative barrier loci in future speciation work.
|
|
| 10. |
- Kulmuni, J., et al.
(författare)
-
Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers
- 2020
-
Ingår i: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. - : The Royal Society. - 1471-2970. ; 375:1806
-
Tidskriftsartikel (refereegranskat)abstract
- Speciation, that is, the evolution of reproductive barriers eventually leading to complete isolation, is a crucial process generating biodiversity. Recent work has contributed much to our understanding of how reproductive barriers begin to evolve, and how they are maintained in the face of gene flow. However, little is known about the transition from partial to strong reproductive isolation (RI) and the completion of speciation. We argue that the evolution of strong RI is likely to involve different processes, or new interactions among processes, compared with the evolution of the first reproductive barriers. Transition to strong RI may be brought about by changing external conditions, for example, following secondary contact. However, the increasing levels of RI themselves create opportunities for new barriers to evolve and, and interaction or coupling among barriers. These changing processes may depend on genomic architecture and leave detectable signals in the genome. We outline outstanding questions and suggest more theoretical and empirical work, considering both patterns and processes associated with strong RI, is needed to understand how speciation is completed. This article is part of the theme issue 'Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers'.
|
|
| 11. |
- Lucek, K., et al.
(författare)
-
Secondary contact zones of closely-relatedErebiabutterflies overlap with narrow phenotypic and parasitic clines
- 2020
-
Ingår i: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 33:9, s. 1152-1163
-
Tidskriftsartikel (refereegranskat)abstract
- Zones of secondary contact between closely related taxa are a common legacy of the Quaternary ice ages. Despite their abundance, the factors that keep species apart and prevent hybridization are often unknown. Here, we study a very narrow contact zone between three closely related butterfly species of theErebia tyndarusspecies complex. Using genomic data, we first determined whether gene flow occurs and then assessed whether it might be hampered by differences in chromosome number between some species. We found interspecific gene flow between sibling species that differ in karyotype by one chromosome. Conversely, only F1 hybrids occurred between two species that have the same karyotype, forming a steep genomic cline. In a second step, we fitted clines to phenotypic, ecological and parasitic data to identify the factors associated with the genetic cline. We found clines for phenotypic data and the prevalence of the endosymbiont parasiteWolbachiato overlap with the genetic cline, suggesting that they might be drivers for separating the two species. Overall, our results highlight that some gene flow is possible between closely related species despite different chromosome numbers, but that other barriers restrict such gene flow.
|
|
| 12. |
- Meirmans, S., et al.
(författare)
-
Science policies: How should science funding be allocated? An evolutionary biologists' perspective
- 2019
-
Ingår i: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 32:8, s. 754-768
-
Tidskriftsartikel (refereegranskat)abstract
- In an ideal world, funding agencies could identify the best scientists and projects and provide them with the resources to undertake these projects. Most scientists would agree that in practice, how funding for scientific research is allocated is far from ideal and likely compromises research quality. We, nine evolutionary biologists from different countries and career stages, provide a comparative summary of our impressions on funding strategies for evolutionary biology across eleven different funding agencies. We also assess whether and how funding effectiveness might be improved. We focused this assessment on 14 elements within four broad categories: (a) topical shaping of science, (b) distribution of funds, (c) application and review procedures, and (d) incentives for mobility and diversity. These comparisons revealed striking among-country variation in those elements, including wide variation in funding rates, the effort and burden required for grant applications, and the extent of emphasis on societal relevance and individual mobility. We use these observations to provide constructive suggestions for the future and urge the need to further gather informed considerations from scientists on the effects of funding policies on science across countries and research fields.
|
|
| 13. |
- Parker, D. J., et al.
(författare)
-
Inter and Intraspecific Genomic Divergence in Drosophila montana Shows Evidence for Cold Adaptation
- 2018
-
Ingår i: Genome Biology and Evolution. - : Oxford University Press (OUP). - 1759-6653. ; 10:8, s. 2086-2101
-
Tidskriftsartikel (refereegranskat)abstract
- The genomes of species that are ecological specialists will likely contain signatures of genomic adaptation to their niche. However, distinguishing genes related to ecological specialism from other sources of selection and more random changes is a challenge. Here, we describe the genome of Drosophila montana, which is the most extremely cold-adapted Drosophila species known. We use branch tests to identify genes showing accelerated divergence in contrasts between cold- and warm-adapted species and identify about 250 genes that show differences, possibly driven by a lower synonymous substitution rate in cold- adapted species. We also look for evidence of accelerated divergence between D. montana and D.virilis. a previously sequenced relative, but do not find strong evidence for divergent selection on coding sequence variation. Divergent genes are involved in a variety of functions, including cuticular and olfactory processes. Finally, we also resequenced three populations of D. montana from across its ecological and geographic range. Outlier loci were more likely to be found on the X chromosome and there was a greater than expected overlap between population outliers and those genes implicated in cold adaptation between Drosophila species, implying some continuity of selective process at these different evolutionary scales.
|
|
| 14. |
- Plowright, Alleyn T., et al.
(författare)
-
Design and synthesis of a novel series of cyclohexyloxy-pyridyl derivatives as inhibitors of diacylglycerol acyl transferase 1
- 2013
-
Ingår i: MedChemComm. - : Royal Society of Chemistry (RSC). - 2040-2503 .- 2040-2511. ; 4:1, s. 151-158
-
Tidskriftsartikel (refereegranskat)abstract
- A novel series of potent diacylglycerol acyl transferase 1 inhibitors was developed from the clinical candidate AZD3988. Replacement of the phenyl cyclohexyl-ethanoate side chain with substituted oxy-linked side chains to introduce changes in shape and polarity, reduce lipophilicity and mask the hydrogen bond donors with internal hydrogen bond acceptors led to improvements in solubility, unbound clearance and excellent selectivity over the related enzyme acyl-coenzyme A:cholesterol acyltransferase 1. A comparison of the small molecule crystal structures of compound 4 and compound 28 is described. Compounds in this series have good ADMET properties and provide an exposure-dependent decrease in circulating plasma triglyceride levels in a rat oral lipid tolerance test.
|
|
| 15. |
- Porcelli, D., et al.
(författare)
-
The environmental genomics of metazoan thermal adaptation
- 2015
-
Ingår i: Heredity. - : Springer Science and Business Media LLC. - 0018-067X .- 1365-2540. ; 114:5, s. 502-514
-
Forskningsöversikt (refereegranskat)abstract
- Continued and accelerating change in the thermal environment places an ever-greater priority on understanding how organisms are going to respond. The paradigm of 'move, adapt or die', regarding ways in which organisms can respond to environmental stressors, stimulates intense efforts to predict the future of biodiversity. Assuming that extinction is an unpalatable outcome, researchers have focussed attention on how organisms can shift in their distribution to stay in the same thermal conditions or can stay in the same place by adapting to a changing thermal environment. How likely these respective outcomes might be depends on the answer to a fundamental evolutionary question, namely what genetic changes underpin adaptation to the thermal environment. The increasing access to and decreasing costs of next-generation sequencing (NGS) technologies, which can be applied to both model and non-model systems, provide a much-needed tool for understanding thermal adaptation. Here we consider broadly what is already known from non-NGS studies about thermal adaptation, then discuss the benefits and challenges of different NGS methodologies to add to this knowledge base. We then review published NGS genomics and transcriptomics studies of thermal adaptation to heat stress in metazoans and compare these results with previous non-NGS patterns. We conclude by summarising emerging patterns of genetic response and discussing future directions using these increasingly common techniques.
|
|
| 16. |
- Smadja, Carole M, et al.
(författare)
-
Large-scale candidate gene scan reveals the role of chemoreceptor genes in host plant specialisation and speciation in the pea aphid
- 2012
-
Ingår i: Evolution. - : Wiley. - 1558-5646 .- 0014-3820. ; 66:9, s. 2723-2738
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the drivers of speciation is critical to interpreting patterns of biodiversity. The identification of the genetic changes underlying adaptation and reproductive isolation is necessary to link barriers to gene flow to the causal origins of divergence. Here, we present a novel approach to the genetics of speciation, which should complement the commonly used approaches of quantitative trait locus mapping and genome-wide scans for selection. We present a large-scale candidate gene approach by means of sequence capture, applied to identifying the genetic changes underlying reproductive isolation in the pea aphid, a model system for the study of ecological speciation. Targeted resequencing enabled us to scale up the candidate gene approach, specifically testing for the role of chemosensory gene families in host plant specialization. Screening for the signature of divergence under selection at 172 candidate and noncandidate loci, we revealed a handful of loci that show high levels of differentiation among host races, which almost all correspond to odorant and gustatory receptor genes. This study offers the first indication that some chemoreceptor genes, often tightly linked together in the genome, could play a key role in local adaptation and reproductive isolation in the pea aphid and potentially other phytophagous insects. Our approach opens a new route toward the functional genomics of ecological speciation.
|
|
| 17. |
- Tusso Gomez, Sergio Ivan
(författare)
-
Adaptive divergence in fission yeast : From experimental evolution to evolutionary genomics
- 2019
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- How adaptation and population differentiation occur is fundamental to understand the origin of biodiversity. Work in speciation alongside the increased ease of generating genomic data have allowed the exploration of genomic changes relevant to adaptation. However, it remains challenging to infer the underlying mechanisms from genomic patterns of divergence governed by both genomic properties and external selective pressures. The chronological order of genomic changes, evolutionary history and selective forces can rarely be inferred from natural populations.Currently, I see two promising ways to tackle the problem of the genomic underpinnings of divergence: (1) evolution experiments simulating adaptation and population divergence and measuring genomic changes as they occur through time; (2) empirical studies of closely related populations in which the extent of divergence varies, allowing us to infer the chronology of the genomic changes. In my Ph.D. research I applied these two approaches, using the fungus Schizosaccharomyces pombe. First, I experimentally tested the potential for ecological divergence with gene flow, and investigated genomic and phenotypic changes associated with this process. Next, I studied genomic data obtained from natural populations sampled worldwide. In both cases, the genetic inference relied on different sequencing technologies including the Illumina, Pacific Biosciences and Oxford Nanopore platforms.The experiment explored the effect of gene flow on phenotype and fitness, and uncovered potential molecular mechanisms underlying adaptive divergence. In paper I we demonstrate the emergence of specialisation under low gene flow, but generalist strategies when gene flow was high. Evolved phenotypes were largely influenced by standing genetic variation subject to opposite antagonistic pleiotropy complemented by new mutations enriched in a subset of genes. In paper II, we show that the experimental selective regime also had an effect on mating strategies, result of temporal ecological heterogeneity and selection for mating efficiency. We found that the evolution of mating strategies was explained by a trade-off between mating efficiency and asexual growth rate dependent on environmental stability. Papers III and IV consider the role of gene flow in natural populations. In paper III, we provide evidence that gene flow also played a predominant role in adaptive divergence in nature. All strains resulted from recent hybridization between two ancestral groups manifested in large phenotypic variation and reproductive isolation.This demographic history of hybridization was confirmed in paper IV focusing on patterns of mitochondrial diversity, adding evidence for the geographic distribution of the ancestral populations and potential for horizontal gene transfer from a distant yeast clade.
|
|
| 18. |
- Wright, Dominic, et al.
(författare)
-
Epistatic regulation of behavioural and morphological traits in the zebrafish (Danio rerio)
- 2006
-
Ingår i: Behavior Genetics. - : Springer Science and Business Media LLC. - 0001-8244 .- 1573-3297. ; 36:6, s. 914-922
-
Tidskriftsartikel (refereegranskat)abstract
- There is currently a lack of studies examining epistasis in general, and specifically for behavioural traits of evolutionary significance. The advent of more efficient analytical methods for exploring epistasis in QTL studies removes the computational restraint on this type of analysis and suggests that performing further analyses of existing datasets may reveal a more complete picture of the genetic architecture of the traits. Here we report the results from an epistatic QTL analysis of an F2 cross between a wild population and a standard laboratory strain of zebrafish. This further analysis was performed using a simultaneous search to identify epistatically interacting QTL affecting behavioural and morphological traits and uncovered several novel epistatic interactions that reached either genome-wide or suggestive significance levels as determined by a randomisation testing approach. These results provide novel insight into the genetic architecture of the regulation of behavioural as well as morphological phenotypes and call for more studies of epistasis for this group of traits.
|
|
