| 1. |
- Clark, Andrew G., et al.
(författare)
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Evolution of genes and genomes on the Drosophila phylogeny
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 450:7167, s. 203-218
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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.
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| 2. |
- Seehausen, Ole, et al.
(författare)
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Genomics and the origin of species
- 2014
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Ingår i: Nature reviews genetics. - : Springer Science and Business Media LLC. - 1471-0056 .- 1471-0064. ; 15:3, s. 176-192
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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.
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| 3. |
- Barlind, Jonas G, et al.
(författare)
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Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687)
- 2012
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 55:23, s. 10610-10629
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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.
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| 4. |
- Duvaux, L., et al.
(författare)
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Dynamics of copy number variation in host races of the pea aphid
- 2015
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Ingår i: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 32:1, s. 63-80
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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.
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| 5. |
- Fountain, Toby, et al.
(författare)
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A Linkage Map and QTL Analysis for Pyrethroid Resistance in the Bed Bug Cimex lectularius
- 2016
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Ingår i: G3-Genes Genomes Genetics. - : Oxford University Press (OUP). - 2160-1836. ; 6:12, s. 4059-4066
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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.
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| 6. |
- Fountain, T., et al.
(författare)
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Outbreeding effects in an inbreeding insect, Cimex lectularius
- 2015
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 5:2, s. 409-418
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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.
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| 7. |
- Hearn, K. E., et al.
(författare)
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Differing associations between sex determination and sex-linked inversions in two ecotypes of Littorina saxatilis
- 2022
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Ingår i: Evolution Letters. - : Oxford University Press (OUP). - 2056-3744. ; 6:5, s. 358-74
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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.
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| 8. |
- Kawakami, Takeshi, et al.
(författare)
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Hybrid Zones
- 2012
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Ingår i: eLS. - : John Wiley & Sons. - 9780470015902
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Bokkapitel (refereegranskat)
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| 9. |
- Kulmuni, J., et al.
(författare)
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Instability of natural selection at candidate barrier loci underlying speciation in wood ants
- 2020
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 29:20, s. 3988-3999
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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.
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| 10. |
- Kulmuni, J., et al.
(författare)
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Towards the completion of speciation: the evolution of reproductive isolation beyond the first barriers
- 2020
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Ingår i: Philosophical transactions of the Royal Society of London. Series B, Biological sciences. - : The Royal Society. - 1471-2970. ; 375:1806
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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'.
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