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  • 1.
    Forslund, Kristoffer
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Henricson, Anna
    Hollich, Volker
    Sonnhammer, Erik L.L.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Domain tree-based analysis of protein architecture evolution2008In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 25, no 2, p. 254-264Article in journal (Refereed)
    Abstract [en]

    Understanding the dynamics behind domain architecture evolution is of great importance to unravel the functions of proteins. Complex architectures have been created throughout evolution by rearrangement and duplication events. An interesting question is how many times a particular architecture has been created, a form of convergent evolution or domain architecture reinvention. Previous studies have approached this issue by comparing architectures found in different species. We wanted to achieve a finer-grained analysis by reconstructing protein architectures on complete domain trees. The prevalence of domain architecture reinvention in 96 genomes was investigated with a novel domain tree-based method that uses maximum parsimony for inferring ancestral protein architectures. Domain architectures were taken from Pfam. To ensure robustness, we applied the method to bootstrap trees and only considered results with strong statistical support. We detected multiple origins for 12.4% of the scored architectures. In a much smaller data set, the subset of completely domain-assigned proteins, the figure was 5.6%. These results indicate that domain architecture reinvention is a much more common phenomenon than previously thought. We also determined which domains are most frequent in multiply created architectures and assessed whether specific functions could be attributed to them. However, no strong functional bias was found in architectures with multiple origins.

  • 2.
    Höhna, Sebastian
    et al.
    Stockholm University, Faculty of Science, Department of Mathematics.
    Stadler, Tanja
    Ronquist, Fredrik
    Britton, Tom
    Stockholm University, Faculty of Science, Department of Mathematics.
    Inferring Speciation and Extinction Rates under Different Sampling Schemes2011In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 28, no 9, p. 2577-2589Article in journal (Refereed)
    Abstract [en]

    The birth-death process is widely used in phylogenetics to model speciation and extinction. Recent studies have shown that the inferred rates are sensitive to assumptions about the sampling probability of lineages. Here, we examine the effect of the method used to sample lineages. Whereas previous studies have assumed random sampling (RS), we consider two extreme cases of biased sampling: diversified sampling (DS), where tips are selected to maximize diversity and cluster sampling (CS), where sample diversity is minimized. DS appears to be standard practice, for example, in analyses of higher taxa, whereas CS may occur under special circumstances, for example, in studies of geographically defined floras or faunas. Using both simulations and analyses of empirical data, we show that inferred rates may be heavily biased if the sampling strategy is not modeled correctly. In particular, when a diversified sample is treated as if it were a random or complete sample, the extinction rate is severely underestimated, often close to 0. Such dramatic errors may lead to serious consequences, for example, if estimated rates are used in assessing the vulnerability of threatened species to extinction. Using Bayesian model testing across 18 empirical data sets, we show that DS is commonly a better fit to the data than complete, random, or cluster sampling (CS). Inappropriate modeling of the sampling method may at least partly explain anomalous results that have previously been attributed to variation over time in birth and death rates.

  • 3.
    Light, Sara
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Sagit, Rauan
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Sachenkova, Oxana
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Ekman, Diana
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Protein Expansion Is Primarily due to Indels in Intrinsically Disordered Regions2013In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 30, no 12, p. 2645-2653Article in journal (Refereed)
    Abstract [en]

    Proteins evolve not only through point mutations but also by insertion and deletion events, which affect the length of the protein. It is well known that such indel events most frequently occur in surface-exposed loops. However, detailed analysis of indel events in distantly related and fast-evolving proteins is hampered by the difficulty involved in correctly aligning such sequences. Here, we circumvent this problem by first only analyzing homologous proteins based on length variation rather than pairwise alignments. Using this approach, we find a surprisingly strong relationship between difference in length and difference in the number of intrinsically disordered residues, where up to three quarters of the length variation can be explained by changes in the number of intrinsically disordered residues. Further, we find that disorder is common in both insertions and deletions. A more detailed analysis reveals that indel events do not induce disorder but rather that already disordered regions accrue indels, suggesting that there is a lowered selective pressure for indels to occur within intrinsically disordered regions.

  • 4. Petrov, Anton S.
    et al.
    Wood, Elizabeth C.
    Bernier, Chad R.
    Norris, Ashlyn M.
    Brown, Alan
    Amunts, Alexey
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Karolinska Institutet, Sweden.
    Structural Patching Fosters Divergence of Mitochondrial Ribosomes2019In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 36, no 2, p. 207-219Article in journal (Refereed)
    Abstract [en]

    Mitochondrial ribosomes (mitoribosomes) are essential components of all mitochondria that synthesize proteins encoded by the mitochondrial genome. Unlike other ribosomes, mitoribosomes are highly variable across species. The basis for this diversity is not known. Here, we examine the composition and evolutionary history of mitoribosomes across the phylogenetic tree by combining three-dimensional structural information with a comparative analysis of the secondary structures of mitochondrial rRNAs (mt-rRNAs) and available proteomic data. We generate a map of the acquisition of structural variation and reconstruct the fundamental stages that shaped the evolution of the mitoribosomal large subunit and led to this diversity. Our analysis suggests a critical role for ablation and expansion of rapidly evolving mt-rRNA. These changes cause structural instabilities that are patched by the acquisition of pre-existing compensatory elements, thus providing opportunities for rapid evolution. This mechanism underlies the incorporation of mt-tRNA into the central protuberance of the mammalian mitoribosome, and the altered path of the polypeptide exit tunnel of the yeast mitoribosome. We propose that since the toolkits of elements utilized for structural patching differ between mitochondria of different species, it fosters the growing divergence of mitoribosomes.

  • 5. Renault, Hugues
    et al.
    De Marothy, Minttu
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Jonasson, Gabriella
    Lara, Patricia
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Nelson, David R.
    Nilsson, IngMarie
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Andre, Francois
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Werck-Reichhart, Danièle
    Gene Duplication Leads to Altered Membrane Topology of a Cytochrome P450 Enzyme in Seed Plants2017In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 34, no 8, p. 2041-2056Article in journal (Refereed)
    Abstract [en]

    Evolution of the phenolic metabolism was critical for the transition of plants from water to land. A cytochrome P450, CYP73, with cinnamate 4-hydroxylase (C4H) activity, catalyzes the first plant-specific and rate-limiting step in this pathway. The CYP73 gene is absent from green algae, and first detected in bryophytes. A CYP73 duplication occurred in the ancestor of seed plants and was retained in Taxaceae and most angiosperms. In spite of a clear divergence in primary sequence, both paralogs can fulfill comparable cinnamate hydroxylase roles both in vitro and in vivo. One of them seems dedicated to the biosynthesis of lignin precursors. Its N-terminus forms a single membrane spanning helix and its properties and length are highly constrained. The second is characterized by an elongated and variable N-terminus, reminiscent of ancestral CYP73s. Using as proxies the Brachypodium distachyon proteins, we show that the elongation of the N-terminus does not result in an altered subcellular localization, but in a distinct membrane topology. Insertion in the membrane of endoplasmic reticulum via a double-spanning open hairpin structure allows reorientation to the lumen of the catalytic domain of the protein. In agreement with participation to a different functional unit and supramolecular organization, the protein displays modified heme proximal surface. These data suggest the evolution of divergent C4H enzymes feeding different branches of the phenolic network in seed plants. It shows that specialization required for retention of gene duplicates may result from altered protein topology rather than change in enzyme activity.

  • 6. Steige, Kim A.
    et al.
    Reimegard, Johan
    Koenig, Daniel
    Scofield, Douglas G.
    Slotte, Tanja
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Cis-Regulatory Changes Associated with a Recent Mating System Shift and Floral Adaptation in Capsella2015In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 32, no 10, p. 2501-2514Article in journal (Refereed)
    Abstract [en]

    The selfing syndrome constitutes a suite of floral and reproductive trait changes that have evolved repeatedly across many evolutionary lineages in response to the shift to selfing. Convergent evolution of the selfing syndrome suggests that these changes are adaptive, yet our understanding of the detailed molecular genetic basis of the selfing syndrome remains limited. Here, we investigate the role of cis-regulatory changes during the recent evolution of the selfing syndrome in Capsella rubella, which split from the outcrosser Capsella grandiflora less than 200 ka. We assess allele-specific expression (ASE) in leaves and flower buds at a total of 18,452 genes in three interspecific F1 C. grandiflora x C. rubella hybrids. Using a hierarchical Bayesian approach that accounts for technical variation using genomic reads, we find evidence for extensive cis-regulatory changes. On average, 44% of the assayed genes show evidence of ASE; however, only 6% show strong allelic expression biases. Flower buds, but not leaves, show an enrichment of cis-regulatory changes in genomic regions responsible for floral and reproductive trait divergence between C. rubella and C. grandiflora. We further detected an excess of heterozygous transposable element (TE) insertions near genes with ASE, and TE insertions targeted by uniquely mapping 24-nt small RNAs were associated with reduced expression of nearby genes. Our results suggest that cis-regulatory changes have been important during the recent adaptive floral evolution in Capsella and that differences in TE dynamics between selfing and outcrossing species could be important for rapid regulatory divergence in association with mating system shifts.

  • 7. Sverrisdottir, Oddny Osk
    et al.
    Timpson, Adrian
    Toombs, Jamie
    Lecoeur, Cecile
    Froguel, Philippe
    Miguel Carretero, Jose
    Arsuaga Ferreras, Juan Luis
    Götherström, Anders
    Stockholm University, Faculty of Humanities, Department of Archaeology and Classical Studies, Archaeological Research Laboratory.
    Thomas, Mark G.
    Direct Estimates of Natural Selection in Iberia Indicate Calcium Absorption Was Not the Only Driver of Lactase Persistence in Europe2014In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 31, no 4, p. 975-983Article in journal (Refereed)
    Abstract [en]

    Lactase persistence (LP) is a genetically determined trait whereby the enzyme lactase is expressed throughout adult life. Lactase is necessary for the digestion of lactose-the main carbohydrate in milk-and its production is downregulated after the weaning period in most humans and all other mammals studied. Several sources of evidence indicate that LP has evolved independently, in different parts of the world over the last 10,000 years, and has been subject to strong natural selection in dairying populations. In Europeans, LP is strongly associated with, and probably caused by, a single C to T mutation 13,910 bp upstream of the lactase (LCT) gene (-13,910*T). Despite a considerable body of research, the reasons why LP should provide such a strong selective advantage remain poorly understood. In this study, we examine one of the most widely cited hypotheses for selection on LP-that fresh milk consumption supplemented the poor vitamin D and calcium status of northern Europe's early farmers (the calcium assimilation hypothesis). We do this by testing for natural selection on -13,910*T using ancient DNA data from the skeletal remains of eight late Neolithic Iberian individuals, whom we would not expect to have poor vitamin D and calcium status because of relatively high incident UVB light levels. None of the eight samples successfully typed in the study had the derived T-allele. In addition, we reanalyze published data from French Neolithic remains to both test for population continuity and further examine the evolution of LP in the region. Using simulations that accommodate genetic drift, natural selection, uncertainty in calibrated radiocarbon dates, and sampling error, we find that natural selection is still required to explain the observed increase in allele frequency. We conclude that the calcium assimilation hypothesis is insufficient to explain the spread of LP in Europe.

  • 8.
    Warshan, Denis
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Liaimer, Anton
    Pederson, Eric
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Kim, Sea-Yong
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Shapiro, Nicole
    Woyke, Tanja
    Altermark, Bjorn
    Pawlowski, Katharina
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Weyman, Philip D.
    Dupont, Christopher L.
    Rasmussen, Ulla
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Genomic Changes Associated With the Evolutionary Transitions of Nostoc to a Plant Symtiont2018In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 35, no 5, p. 1160-1175Article in journal (Refereed)
    Abstract [en]

    Cyanobacteria belonging to the genus Nostoc comprise free-living strains and also facultative plant symbionts. Symbiotic strains can enter into symbiosis with taxonomically diverse range of host plants. Little is known about genomic changes associated with evolutionary transition of Nostoc from free-living to plant symbiont. Here, we compared the genomes derived from 11 symbiotic Nostoc strains isolated from different host plants and infer phylogenetic relationships between strains. Phylogenetic reconstructions of 89 Nostocales showed that symbiotic Nostoc strains with a broad host range, entering epiphytic and intracellular or extracellular endophytic interactions, form a monophyletic Glade indicating a common evolutionary history. A polyphyletic origin was found for Nostoc strains which enter only extracellular symbioses, and inference of transfer events implied that this trait was likely acquired several times in the evolution of the Nostocales. Symbiotic Nostoc strains showed enriched functions in transport and metabolism of organic sulfur, chemotaxis and motility, as well as the uptake of phosphate, branched-chain amino acids, and ammonium. The genomes of the intracellular Glade differ from that of other Nostoc strains, with a gain/enrichment of genes encoding proteins to generate i-methionine from sulfite and pathways for the degradation of the plant metabolites vanillin and vanillate, and of the macromolecule xylan present in plant cell walls. These compounds could function as C-sources for members of the intracellular Glade. Molecular clock analysis indicated that the intracellular Glade emerged ca. 600 Ma, suggesting that intracellular Nostoc symbioses predate the origin of land plants and the emergence of their extant hosts.

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