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Berglund, Jonas
Publications (10 of 12) Show all publications
Lamichhaney, S., Han, F., Berglund, J., Wang, C., Sällman Almen, M., T. Webster, M., . . . Andersson, L. (2016). A beak size locus in Darwin’s finches facilitated character displacement during a drought. Science, 352(6284), 470-474
Open this publication in new window or tab >>A beak size locus in Darwin’s finches facilitated character displacement during a drought
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2016 (English)In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 352, no 6284, p. 470-474Article in journal (Refereed) Published
Abstract [en]

Ecological character displacement is a process of morphological divergence that reducescompetition for limited resources. We used genomic analysis to investigate the geneticbasis of a documented character displacement event in Darwin’s finches on Daphne Majorin the Galápagos Islands: The medium ground finch diverged from its competitor, the largeground finch, during a severe drought. We discovered a genomic region containing theHMGA2gene that varies systematically among Darwin’s finch species with different beaksizes. Two haplotypes that diverged early in the radiation were involved in the characterdisplacement event: Genotypes associated with large beak size were at a strong selectivedisadvantage in medium ground finches (selection coefficients= 0.59). Thus, a majorlocus has apparently facilitated a rapid ecological diversification in the adaptive radiationof Darwin’s finches.

National Category
Genetics and Breeding
Identifiers
urn:nbn:se:uu:diva-279968 (URN)10.1126/science.aad8786 (DOI)000374479700050 ()27102486 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationSwedish Research Council, 80576801Swedish Research Council, 70374401
Available from: 2016-03-06 Created: 2016-03-06 Last updated: 2017-11-30Bibliographically approved
Almén, M. S., Lamichhaney, S., Berglund, J., Grant, B. R., Grant, P. R., Webster, M. T. & Andersson, L. (2016). Adaptive radiation of Darwin's finches revisited using whole genome sequencing. Bioessays, 38(1), 14-20
Open this publication in new window or tab >>Adaptive radiation of Darwin's finches revisited using whole genome sequencing
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2016 (English)In: Bioessays, ISSN 0265-9247, E-ISSN 1521-1878, Vol. 38, no 1, p. 14-20Article in journal (Refereed) Published
Abstract [en]

We recently used genome sequencing to study the evolutionary history of the Darwin's finches. A prominent feature of our data was that different polymorphic sites in the genome tended to indicate different genetic relationships among these closely related species. Such patterns are expected in recently diverged genomes as a result of incomplete lineage sorting. However, we uncovered conclusive evidence that these patterns have also been influenced by interspecies hybridisation, a process that has likely played an important role in the radiation of Darwin's finches. A major discovery was that segregation of two haplotypes at the ALX1 locus underlies variation in beak shape among the Darwin's finches, and that differences between the two haplotypes in a 240 kb region in blunt and pointed beaked birds involve both coding and regulatory changes. As we review herein, the evolution of such adaptive haplotypes comprising multiple causal changes appears to be an important mechanism contributing to the evolution of biodiversity.

Keywords
adaptation, evolution, gene flow, genome sequencing
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-282647 (URN)10.1002/bies.201500079 (DOI)000371265200004 ()26606649 (PubMedID)
Available from: 2016-04-06 Created: 2016-04-06 Last updated: 2017-11-30Bibliographically approved
Imsland, F., McGowan, K., Rubin, C.-J., Henegar, C., Sundström, E., Berglund, J., . . . Andersson, L. (2016). Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation underlying Dun camouflage colour in horses. Nature Genetics, 48(2), 152-158
Open this publication in new window or tab >>Regulatory mutations in TBX3 disrupt asymmetric hair pigmentation underlying Dun camouflage colour in horses
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2016 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, no 2, p. 152-158Article in journal (Refereed) Published
Abstract [en]

Dun is a wild-type coat color in horses characterized by pigment dilution with a striking pattern of dark areas termed primitive markings. Here we show that pigment dilution in Dun horses is due to radially asymmetric deposition of pigment in the growing hair caused by localized expression of the T-box 3 (TBX3) transcription factor in hair follicles, which in turn determines the distribution of hair follicle melanocytes. Most domestic horses are non-dun, a more intensely pigmented phenotype caused by regulatory mutations impairing TBX3 expression in the hair follicle, resulting in a more circumferential distribution of melanocytes and pigment granules in individual hairs. We identified two different alleles (non-dun1 and non-dun2) causing non-dun color. non-dun2 is a recently derived allele, whereas the Dun and non-dun1 alleles are found in ancient horse DNA, demonstrating that this polymorphism predates horse domestication. These findings uncover a new developmental role for T-box genes and new aspects of hair follicle biology and pigmentation.

National Category
Genetics Cell Biology
Identifiers
urn:nbn:se:uu:diva-254473 (URN)10.1038/ng.3475 (DOI)000369043900012 ()26691985 (PubMedID)
Funder
Knut and Alice Wallenberg FoundationNIH (National Institute of Health)Swedish Research Council, 80576801Swedish Research Council, 70374401Science for Life Laboratory - a national resource center for high-throughput molecular bioscience
Available from: 2015-08-10 Created: 2015-06-08 Last updated: 2017-12-04Bibliographically approved
Lamichhaney, S., Berglund, J., Almen, M. S., Maqbool, K., Grabherr, M., Martinez-Barrio, A., . . . Andersson, L. (2015). Evolution of Darwin's finches and their beaks revealed by genome sequencing. Nature, 518(7539)
Open this publication in new window or tab >>Evolution of Darwin's finches and their beaks revealed by genome sequencing
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2015 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7539Article in journal (Refereed) Published
Abstract [en]

Darwin's finches, inhabiting the Galapagos archipelago and Cocos Island, constitute an iconic model for studies of speciation and adaptive evolution. Here we report the results of whole-genome re-sequencing of 120 individuals representing all of the Darwin's finch species and two close relatives' Phylogenetic analysis reveals important discrepancies with the phenotype-based taxonomy. We find extensive evidence for interspecific gene flow throughout the radiation. Hybridization has given rise to species of mixed ancestry. A 240 kilobase haplotype encompassing the ALX1 gene that encodes a transcription factor affecting craniofacial. development is strongly associated with beak shape diversity across Darwin's finch species as well as within the medium ground finch (Geospiza fortis) a species that has undergone rapid evolution of beak shape in response to environmental changes. The ALX1 haplotype has contributed to diversification of beak shapes among the Darwin's finches and thereby, to an expanded utilization of food resources.

National Category
Medical Genetics Microbiology in the medical area
Identifiers
urn:nbn:se:uu:diva-247384 (URN)10.1038/nature14181 (DOI)000349547400036 ()25686609 (PubMedID)
Available from: 2015-03-20 Created: 2015-03-18 Last updated: 2018-01-11Bibliographically approved
Berglund, J., Quilez, J., Arndt, P. F. & Webster, M. T. (2015). Germ line Methylation Patterns Determine the Distribution of Recombination Events in the Dog Genome. Genome Biology and Evolution, 7(2), 522-530
Open this publication in new window or tab >>Germ line Methylation Patterns Determine the Distribution of Recombination Events in the Dog Genome
2015 (English)In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 7, no 2, p. 522-530Article in journal (Refereed) Published
Abstract [en]

The positive-regulatory domain containing nine gene, PROMO, which strongly associates with the location of recombination events in several vertebrates, is inferred to be inactive in the dog genome. Here, we address several questions regarding the control of recombination and its influence on genome evolution in dogs. First, we address whether the association between CpG islands (CGIs) and recombination hotspots is generated by lack of methylation, GC-biased gene conversion (gBGC), or both. Using a genome-wide dog single nucleotide polymorphism data set and comparisons of the dog genome with related species, we show that recombination-associated CGIs have low CpG mutation rates, and that CpG mutation rate is negatively correlated with recombination rate genome wide, indicating that nonmethylation attracts the recombination machinery. We next use a neighbor-dependent model of nucleotide substitution to disentangle the effects of CpG mutability and gBGC and analyze the effects that loss of PROMO has on these rates. We infer that methylation patterns have been stable during canid genome evolution, but that dog CGIs have experienced a drastic increase in substitution rate due to gBGC, consistent with increased levels of recombination in these regions. We also show that gBGC is likely to have generated many new CGIs in the dog genome, but these mostly occur away from genes, whereas the number of C GIs in gene promoter regions has not increased greatly in recent evolutionary history. Recombination has a major impact on the distribution of CGIs that are detected in the dog genome due to the interaction between methylation and gBGC. The results indicate that germline methylation patterns are the main determinant of recombination rates in the absence of PRDM9.

Keywords
recombination, biased gene conversion, methylation, dog genome, CpG island
National Category
Medical Genetics
Identifiers
urn:nbn:se:uu:diva-251845 (URN)10.1093/gbe/evu282 (DOI)000351607800009 ()25527838 (PubMedID)
Available from: 2015-04-24 Created: 2015-04-24 Last updated: 2018-01-11Bibliographically approved
Ramirez, O., Olalde, I., Berglund, J., Lorente-Galdos, B., Hernandez-Rodriguez, J., Quilez, J., . . . Marques-Bonet, T. (2014). Analysis of structural diversity in wolf-like canids reveals post-domestication variants. BMC Genomics, 15, 465
Open this publication in new window or tab >>Analysis of structural diversity in wolf-like canids reveals post-domestication variants
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2014 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 15, p. 465-Article in journal (Refereed) Published
Abstract [en]

Background: Although a variety of genetic changes have been implicated in causing phenotypic differences among dogs, the role of copy number variants (CNVs) and their impact on phenotypic variation is still poorly understood. Further, very limited knowledge exists on structural variation in the gray wolf, the ancestor of the dog, or other closely related wild canids. Documenting CNVs variation in wild canids is essential to identify ancestral states and variation that may have appeared after domestication. Results: In this work, we genotyped 1,611 dog CNVs in 23 wolf-like canids (4 purebred dogs, one dingo, 15 gray wolves, one red wolf, one coyote and one golden jackal) to identify CNVs that may have arisen after domestication. We have found an increase in GC-rich regions close to the breakpoints and around 1 kb away from them suggesting that some common motifs might be associated with the formation of CNVs. Among the CNV regions that showed the largest differentiation between dogs and wild canids we found 12 genes, nine of which are related to two known functions associated with dog domestication; growth (PDE4D, CRTC3 and NEB) and neurological function (PDE4D, EML5, ZNF500, SLC6A11, ELAVL2, RGS7 and CTSB). Conclusions: Our results provide insight into the evolution of structural variation in canines, where recombination is not regulated by PRDM9 due to the inactivation of this gene. We also identified genes within the most differentiated CNV regions between dogs and wolves, which could reflect selection during the domestication process.

Keywords
Domestication, CNV, Candidate genes, Dog and wolf
National Category
Evolutionary Biology Genetics
Identifiers
urn:nbn:se:uu:diva-228704 (URN)10.1186/1471-2164-15-465 (DOI)000337701000001 ()
Available from: 2014-07-21 Created: 2014-07-21 Last updated: 2017-12-05Bibliographically approved
Molin, A.-M., Berglund, J., Webster, M. T. & Lindblad-Toh, K. (2014). Genome-wide copy number variant discovery in dogs using the CanineHD genotyping array. BMC Genomics, 15, 210
Open this publication in new window or tab >>Genome-wide copy number variant discovery in dogs using the CanineHD genotyping array
2014 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 15, p. 210-Article in journal (Refereed) Published
Abstract [en]

Background: Substantial contribution to phenotypic diversity is accounted for by copy number variants (CNV). In human, as well as other species, the effect of CNVs range from benign to directly disease-causing which motivates the continued investigations of CNVs. Previous canine genome-wide screenings for CNVs have been performed using high-resolution comparative genomic hybridisation arrays which have contributed with a detailed catalogue of CNVs. Here, we present the first CNV investigation in dogs based on the recently reported CanineHD 170 K genotyping array. The hitherto largest dataset in canine CNV discovery was assessed, 351 dogs from 30 different breeds, enabling identification of novel CNVs and a thorough characterisation of breed-specific CNVs. Results: A stringent procedure identified 72 CNV regions with the smallest size of 38 kb and of the 72 CNV regions, 38 overlapped 148 annotated genes. A total of 29 novel CNV regions were found containing 44 genes. Furthermore, 15 breed specific CNV regions were identified of which 14 were novel and some of them overlapped putative disease susceptibility genes. In addition, the human ortholog of 23 canine copy number variable genes identified herein has been previously suggested to be dosage-sensitive in human. Conclusions: The present study evaluated the performance of the CanineHD in detecting CNVs and extends the current catalogue of canine CNV regions with several dozens of novel CNV regions. These novel CNV regions, which harbour candidate genes that possibly contribute to phenotypic variation in dogs or to disease-susceptibility, are a rich resource for future investigations.

Keywords
Copy number variation, CNV, SNP genotyping array, Dog genome, Deletion, Duplication, CanineHD
National Category
Medical Biotechnology
Identifiers
urn:nbn:se:uu:diva-225098 (URN)10.1186/1471-2164-15-210 (DOI)000334946600001 ()
Available from: 2014-05-27 Created: 2014-05-27 Last updated: 2017-12-05Bibliographically approved
Berglund, J. (2014). Meiotic Recombination in Human and Dog: Targets, Consequences and Implications for Genome Evolution. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Meiotic Recombination in Human and Dog: Targets, Consequences and Implications for Genome Evolution
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Understanding the mechanism of recombination has important implications for genome evolution and genomic variability. The work presented in this thesis studies the properties of recombination by investigating the effects it has on genome evolution in humans and dogs.

Using alignments of human genes with chimpanzee and macaque orthologues we studied substitution patterns along the human lineage and scanned for evidence of positive selection. The properties mirror the situation in human non-coding sequences with the fixation bias ‘GC-biased gene conversion’ (gBGC) as a driving force in the most rapidly evolving regions. By assigning candidate genes to distinct classes of evolutionary forces we quantified the extent of those genes affected by gBGC to 20%. This suggests that human-specific characters can be prompted by the fixation bias of gBGC, which can be mistaken for selection.

The gene PRDM9 controls recombination in most mammals, but is lacking in dogs. Using whole-genome alignments of dog with related species we examined the effects of PRDM9 inactivation. Additionally, we analyzed genomic variation in the genomes of several dog breeds. We identified that non-allelic homologous recombination (NAHR) via sequence identity, often GC-rich, creates structural variants of genomic regions. We show that these regions, which are also found in dog recombination hotspots, are a subset of unmethylated CpG-islands (CGIs). We inferred that CGIs have experienced a drastic increase in biased substitution rates, concurrent with a shift of recombination to target these regions. This enables recurrent episodes of gBGC to shape their distribution.

The work presented in this thesis demonstrates the importance of meiotic recombination on patterns of molecular evolution and genomic variability in humans and dogs. Bioinformatic analyses identified mechanisms that regulate genome composition. gBGC is presented as an alternative to positive selection and is revealed as a major factor affecting allele configuration and the emergence of accelerated evolution on the human lineage. Characterization of recombination-induced sequence patterns highlights the potential of non-methylation and establishes unmethylated CGIs as targets of meiotic recombination in dogs. These observations describe recombination as an interesting process in genome evolution and provide further insights into the mechanisms of genomic variability.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2014. p. 43
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1038
Keywords
recombination, biased gene conversion, CpG island, copy number variation, substitutions, methylation
National Category
Genetics Evolutionary Biology
Research subject
Bioinformatics; Biology with specialization in Evolutionary Genetics; Biology with specialization in Molecular Evolution; Molecular Genetics
Identifiers
urn:nbn:se:uu:diva-233195 (URN)978-91-554-9057-7 (ISBN)
Public defence
2014-11-20, B41, BMC, Husargatan 3, Uppsala, 13:15 (English)
Opponent
Supervisors
Available from: 2014-10-30 Created: 2014-09-30 Last updated: 2015-01-23
Berglund, J., Nevalainen, E. M., Molin, A.-M., Perloski, M., André, C., Zody, M. C., . . . Webster, M. T. (2012). Novel origins of copy number variation in the dog genome. Genome Biology, 13(8), R73
Open this publication in new window or tab >>Novel origins of copy number variation in the dog genome
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2012 (English)In: Genome Biology, ISSN 1465-6906, E-ISSN 1474-760X, Vol. 13, no 8, p. R73-Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Copy number variants (CNVs) account for substantial variation between genomes and are a major source of normal and pathogenic phenotypic differences. The dog is an ideal model to investigate mutational mechanisms that generate CNVs as its genome lacks a functional ortholog of the PRDM9 gene implicated in recombination and CNV formation in humans. Here we comprehensively assay CNVs using high-density array comparative genomic hybridization in 50 dogs from 17 dog breeds and 3 gray wolves. RESULTS: We use a stringent new method to identify a total of 430 high-confidence CNV loci, which range in size from 9 kb to 1.6 Mb and span 26.4 Mb, or 1.08%, of the assayed dog genome, overlapping 413 annotated genes. Of CNVs observed in each breed, 98% are also observed in multiple breeds. CNVs predicted to disrupt gene function are significantly less common than expected by chance. We identify a significant overrepresentation of peaks of GC content, previously shown to be enriched in dog recombination hotspots, in the vicinity of CNV breakpoints. CONCLUSIONS: A number of the CNVs identified by this study are candidates for generating breed-specific phenotypes. Purifying selection seems to be a major factor shaping structural variation in the dog genome, suggesting that many CNVs are deleterious. Localized peaks of GC content appear to be novel sites of CNV formation in the dog genome by non-allelic homologous recombination, potentially activated by the loss of PRDM9. These sequence features may have driven genome instability and chromosomal rearrangements throughout canid evolution.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-194244 (URN)10.1186/gb-2012-13-8-r73 (DOI)000315867500007 ()22916802 (PubMedID)
Note

Additional author: The LUPA Consortium (www.eurolupa.org)

Available from: 2013-02-11 Created: 2013-02-11 Last updated: 2017-12-06Bibliographically approved
Lamichhaney, S., Barrio, A. M., Rafati, N., Sundström, G., Rubin, C.-J., Gilbert, E. R., . . . Andersson, L. (2012). Population-scale sequencing reveals genetic differentiation due to local adaptation in Atlantic herring. Proceedings of the National Academy of Sciences of the United States of America, 109(47), 19345-19350
Open this publication in new window or tab >>Population-scale sequencing reveals genetic differentiation due to local adaptation in Atlantic herring
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2012 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 47, p. 19345-19350Article in journal (Refereed) Published
Abstract [en]

The Atlantic herring (Clupea harengus), one of the most abundant marine fishes in the world, has historically been a critical food source in Northern Europe. It is one of the few marine species that can reproduce throughout the brackish salinity gradient of the Baltic Sea. Previous studies based on few genetic markers have revealed a conspicuous lack of genetic differentiation between geographic regions, consistent with huge population sizes and minute genetic drift. Here, we present a cost-effective genome-wide study in a species that lacks a genome sequence. We first assembled amuscle transcriptome and then aligned genomic reads to the transcripts, creating an "exome assembly," capturing both exons and flanking sequences. We then resequenced pools of fish from a wide geographic range, including the Northeast Atlantic, as well as different regions in the Baltic Sea, aligned the reads to the exome assembly, and identified 440,817 SNPs. The great majority of SNPs showed no appreciable differences in allele frequency among populations; however, several thousand SNPs showed striking differences, some approaching fixation for different alleles. The contrast between low genetic differentiation at most loci and striking differences at others implies that the latter category primarily reflects natural selection. A simulation study confirmed that the distribution of the fixation index F-ST deviated significantly from expectation for selectively neutral loci. This study provides insights concerning the population structure of an important marine fish and establishes the Atlantic herring as a model for population genetic studies of adaptation and natural selection.

Keywords
Baltic herring, genetics, population biology
National Category
Natural Sciences Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-191049 (URN)10.1073/pnas.1216128109 (DOI)000311997200067 ()
Available from: 2013-01-09 Created: 2013-01-09 Last updated: 2017-12-06Bibliographically approved
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