| 11. |
- Künstner, Axel, et al.
(författare)
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Gene content and patterns of gene expression in the flycatcher genome
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Phenotypic evolution may be driven by changes in the sequence of protein-coding genes or by the way (when, where, at what level) proteins are expressed. Generally, our knowledge about the evolution of gene expression is relatively limited, and this is particularly so for wild populations. Collared flycatcher (Ficedula albicollis) and pied flycatcher (F. hypoleuca) are two recently diverged passerine birds, which have been subject to extensive ecological research, including aspects of speciation. We obtained RNA-seq data with Illumina technology from 10 adult individuals per species (five females and five males) using brain, kidney, liver, lung, muscle, skin, ovary, and testis tissue (plus eight embryos of each species). A total of more than 1 billion sequencing reads were assembled into >15.000 gene models for each species. The proportion of differentially expressed genes between species ranged from 8% to 18% per adult tissue. Very few GO categories were found to be overrepresented among differentially expressed genes, which at least in part might reflect that orphan and not yet annotated genes are prone to evolve more rapidly in gene expression level. However, in testis, the category olfactory receptor activity was significantly overrepresented among differentially expressed genes and it is of interest to note that this category of genes is involved in sperm-egg communication and thereby potentially may contribute to reproductive incompatibility between the two species. Genes with a high degree of differentiation in gene expression between species tended to have high rates of sequence evolution (high dN/dS). Overall, this study illustrates both the feasibility and usefulness of deep transcriptome sequencing in non-model organisms.
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| 12. |
- La Fleur, Linnea, et al.
(författare)
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Mutation patterns in a population-based non-small cell lung cancer cohort and prognostic impact of concomitant mutations in KRAS and TP53 or STK11
- 2019
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Ingår i: Lung Cancer. - : Elsevier BV. - 0169-5002 .- 1872-8332. ; 130, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Non-small cell lung cancer (NSCLC) is a heterogeneous disease with unique combinations of somatic molecular alterations in individual patients, as well as significant differences in populations across the world with regard to mutation spectra and mutation frequencies. Here we aim to describe mutational patterns and linked clinical parameters in a population-based NSCLC cohort.MATERIALS AND METHODS: Using targeted resequencing the mutational status of 82 genes was evaluated in a consecutive Swedish surgical NSCLC cohort, consisting of 352 patient samples from either fresh frozen or formalin fixed paraffin embedded (FFPE) tissues. The panel covers all exons of the 82 genes and utilizes reduced target fragment length and two-strand capture making it compatible with degraded FFPE samples.RESULTS: We obtained a uniform sequencing coverage and mutation load across the fresh frozen and FFPE samples by adaption of sequencing depth and bioinformatic pipeline, thereby avoiding a technical bias between these two sample types. At large, the mutation frequencies resembled the frequencies seen in other western populations, except for a high frequency of KRAS hotspot mutations (43%) in adenocarcinoma patients. Worse overall survival was observed for adenocarcinoma patients with a mutation in either TP53, STK11 or SMARCA4. In the adenocarcinoma KRAS-mutated group poor survival appeared to be linked to concomitant TP53 or STK11 mutations, and not to KRAS mutation as a single aberration. Similar results were seen in the analysis of publicly available data from the cBioPortal. In squamous cell carcinoma a worse prognosis could be observed for patients with MLL2 mutations, while CSMD3 mutations were linked to a better prognosis.CONCLUSION: Here we have evaluated the mutational status of a NSCLC cohort. We could not confirm any survival impact of isolated driver mutations. Instead, concurrent mutations in TP53 and STK11 were shown to confer poor survival in the KRAS-positive adenocarcinoma subgroup.
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| 13. |
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| 14. |
- Lamatsch, Dunja K., et al.
(författare)
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A Transcriptome Derived Female-Specific Marker from the Invasive Western Mosquitofish (Gambusia affinis)
- 2015
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Sex-specific markers are a prerequisite for understanding reproductive biology, genetic factors involved in sex differences, mechanisms of sex determination, and ultimately the evolution of sex chromosomes. The Western mosquitofish, Gambusia affinis, may be considered a model species for sex-chromosome evolution, as it displays female heterogamety (ZW/ZZ), and is also ecologically interesting as a worldwide invasive species. Here, de novo RNA-sequencing on the gonads of sexually mature G. affinis was used to identify contigs that were highly transcribed in females but not in males (i.e., transcripts with ovary-specific expression). Subsequently, 129 primer pairs spanning 79 contigs were tested by PCR to identify sex-specific transcripts. Of those primer pairs, one female-specific DNA marker was identified, Sanger sequenced and subsequently validated in 115 fish. Sequence analyses revealed a high similarity between the identified sex-specific marker and the 3' UTR of the aminomethyl transferase (amt) gene of the closely related platyfish (Xiphophorus maculatus). This is the first time that RNA-seq has been used to successfully characterize a sex-specific marker in a fish species in the absence of a genome map. Additionally, the identified sex-specific marker represents one of only a handful of such markers in fishes.
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| 15. |
- Nadachowska-Brzyska, Krystyna, et al.
(författare)
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Demographic Divergence History of Pied Flycatcher and Collared Flycatcher Inferred from Whole-Genome Re-sequencing Data
- 2013
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 9:11, s. e1003942-
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Tidskriftsartikel (refereegranskat)abstract
- Profound knowledge of demographic history is a prerequisite for the understanding and inference of processes involved in the evolution of population differentiation and speciation. Together with new coalescent-based methods, the recent availability of genome-wide data enables investigation of differentiation and divergence processes at unprecedented depth. We combined two powerful approaches, full Approximate Bayesian Computation analysis (ABC) and pairwise sequentially Markovian coalescent modeling (PSMC), to reconstruct the demographic history of the split between two avian speciation model species, the pied flycatcher and collared flycatcher. Using whole-genome re-sequencing data from 20 individuals, we investigated 15 demographic models including different levels and patterns of gene flow, and changes in effective population size over time. ABC provided high support for recent (mode 0.3 my, range <0.7 my) species divergence, declines in effective population size of both species since their initial divergence, and unidirectional recent gene flow from pied flycatcher into collared flycatcher. The estimated divergence time and population size changes, supported by PSMC results, suggest that the ancestral species persisted through one of the glacial periods of middle Pleistocene and then split into two large populations that first increased in size before going through severe bottlenecks and expanding into their current ranges. Secondary contact appears to have been established after the last glacial maximum. The severity of the bottlenecks at the last glacial maximum is indicated by the discrepancy between current effective population sizes (20,000–80,000) and census sizes (5–50 million birds) of the two species. The recent divergence time challenges the supposition that avian speciation is a relatively slow process with extended times for intrinsic postzygotic reproductive barriers to evolve. Our study emphasizes the importance of using genome-wide data to unravel tangled demographic histories. Moreover, it constitutes one of the first examples of the inference of divergence history from genome-wide data in non-model species.
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| 16. |
- Nadachowska-Brzyska, Krystyna, et al.
(författare)
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Genomic inference of contemporary effective population size in a large island population of collared flycatchers (Ficedula albicollis)
- 2021
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Ingår i: Molecular Ecology. - : John Wiley & Sons. - 0962-1083 .- 1365-294X. ; 30:16, s. 3965-3973
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Tidskriftsartikel (refereegranskat)abstract
- Due to its central importance to many aspects of evolutionary biology and population genetics, the long-term effective population size (N-e) has been estimated for numerous species and populations. However, estimating contemporary N-e is difficult and in practice this parameter is often unknown. In principle, contemporary N-e can be estimated using either analyses of temporal changes in allele frequencies, or the extent of linkage disequilibrium (LD) between unlinked markers. We applied these approaches to estimate contemporary N-e of a relatively recently founded island population of collared flycatchers (Ficedula albicollis). We sequenced the genomes of 85 birds sampled in 1993 and 2015, and applied several temporal methods to estimate N-e at a few thousand (4000-7000). The approach based on LD provided higher estimates of N-e (20,000-32,000) and was associated with high variance, often resulting in infinite N-e. We conclude that whole-genome sequencing data offers new possibilities to estimate high (>1000) contemporary N-e, but also note that such estimates remain challenging, in particular for LD-based methods for contemporary N-e estimation.
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| 17. |
- Nadachowska-Brzyska, Krystyna, et al.
(författare)
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PSMC analysis of effective population sizes in molecular ecology and its application to black-and-white Ficedula flycatchers
- 2016
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Ingår i: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 25:5, s. 1058-1072
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Forskningsöversikt (refereegranskat)abstract
- Climatic fluctuations during the Quaternary period governed the demography of species and contributed to population differentiation and ultimately speciation. Studies of these past processes have previously been hindered by a lack of means and genetic data to model changes in effective population size (N-e) through time. However, based on diploid genome sequences of high quality, the recently developed pairwise sequentially Markovian coalescent (PSMC) can estimate trajectories of changes in N-e over considerable time periods. We applied this approach to resequencing data from nearly 200 genomes of four species and several populations of the Ficedula species complex of black-and-white flycatchers. N-e curves of Atlas, collared, pied and semicollared flycatcher converged 1-2million years ago (Ma) at an N-e of approximate to 200000, likely reflecting the time when all four species last shared a common ancestor. Subsequent separate N-e trajectories are consistent with lineage splitting and speciation. All species showed evidence of population growth up until 100-200thousand years ago (kya), followed by decline and then start of a new phase of population expansion. However, timing and amplitude of changes in N-e differed among species, and for pied flycatcher, the temporal dynamics of N-e differed between Spanish birds and central/northern European populations. This cautions against extrapolation of demographic inference between lineages and calls for adequate sampling to provide representative pictures of the coalescence process in different species or populations. We also empirically evaluate criteria for proper inference of demographic histories using PSMC and arrive at recommendations of using sequencing data with a mean genome coverage of 18X, a per-site filter of 10 reads and no more than 25% of missing data.
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| 18. |
- Nadachowska-Brzyska, Krystyna, et al.
(författare)
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Temporal Dynamics of Avian Populations during Pleistocene Revealed by Whole-Genome Sequences
- 2015
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 25:10, s. 1375-1380
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Tidskriftsartikel (refereegranskat)abstract
- Global climate fluctuations have significantly influenced the distribution and abundance of biodiversity [1]. During unfavorable glacial periods, many species experienced range contraction and fragmentation, expanding again during interglacials [2- 4]. An understanding of the evolutionary consequences of both historical and ongoing climate changes requires knowledge of the temporal dynamics of population numbers during such climate cycles. Variation in abundance should have left clear signatures in the patterns of intraspecific genetic variation in extant species, from which historical effective population sizes (Ne) can be estimated [3]. We analyzed whole-genome sequences of 38 avian species in a pairwise sequentially Markovian coalescent (PSMC, [5]) framework to quantitatively reveal changes in Ne from approximately 10 million to 10 thousand years ago. Significant fluctuations in Ne over time were evident for most species. The most pronounced pattern observed in many species was a severe reduction in Ne coinciding with the beginning of the last glacial period (LGP). Among species, Ne varied by at least three orders of magnitude, exceeding 1 million in the most abundant species. Several species on the IUCN Red List of Threatened Species showed long-term reduction in population size, predating recent declines. We conclude that cycles of population expansions and contractions have been a common feature of many bird species during the Quaternary period, likely coinciding with climate cycles. Population size reduction should have increased the risk of extinction but may also have promoted speciation. Species that have experienced long-term declines may be especially vulnerable to recent anthropogenic threats.
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| 19. |
- Nater, Alexander, et al.
(författare)
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Resolving Evolutionary Relationships in Closely Related Species with Whole-Genome Sequencing Data
- 2015
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Ingår i: Systematic Biology. - : Oxford University Press (OUP). - 1063-5157 .- 1076-836X. ; 64:6, s. 1000-1017
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Tidskriftsartikel (refereegranskat)abstract
- Using genetic data to resolve the evolutionary relationships of species is of major interest in evolutionary and systematic biology. However, reconstructing the sequence of speciation events, the so-called species tree, in closely related and potentially hybridizing species is very challenging. Processes such as incomplete lineage sorting and interspecific gene flow result in local gene genealogies that differ in their topology from the species tree, and analyses of few loci with a single sequence per species are likely to produce conflicting or even misleading results. To study these phenomena on a full phylogenomic scale, we use whole-genome sequence data from 200 individuals of four black-and-white flycatcher species with so far unresolved phylogenetic relationships to infer gene tree topologies and visualize genome-wide patterns of gene tree incongruence. Using phylogenetic analysis in nonoverlapping 10-kb windows, we show that gene tree topologies are extremely diverse and change on a very small physical scale. Moreover, we find strong evidence for gene flow among flycatcher species, with distinct patterns of reduced introgression on the Z chromosome. To resolve species relationships on the background of widespread gene tree incongruence, we used four complementary coalescent-based methods for species tree reconstruction, including complex modeling approaches that incorporate post-divergence gene flow among species. This allowed us to infer the most likely species tree with high confidence. Based on this finding, we show that regions of reduced effective population size, which have been suggested as particularly useful for species tree inference, can produce positively misleading species tree topologies. Our findings disclose the pitfalls of using loci potentially under selection as phylogenetic markers and highlight the potential of modeling approaches to disentangle species relationships in systems with large effective population sizes and post-divergence gene flow.
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| 20. |
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