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  • Abdalaal, Hind, et al. (författare)
  • Collateral toxicity limits the evolution of bacterial Release Factor 2 towards total omnipotence
  • 2020
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 37:10, s. 2918-2930
  • Tidskriftsartikel (refereegranskat)abstract
    • When new genes evolve through modification of existing genes, there are often trade-offs between the new and original functions, making gene duplication and amplification necessary to buffer deleterious effects on the original function. We have used experimental evolution of a bacterial strain lacking peptide release factor 1 (RF1) in order to study how peptide release factor 2 (RF2) evolves to compensate the loss of RF1. As expected, amplification of the RF2-encoding gene prfB to high copy number was a rapid initial response, followed by the appearance of mutations in RF2 and other components of the translation machinery. Characterization of the evolved RF2 variants by their effects on bacterial growth rate, reporter gene expression, and in vitro translation termination reveals a complex picture of reduced discrimination between the cognate and near cognate stop codons and highlight a functional trade-off that we term “collateral toxicity”. We suggest that this type of trade-off may be a more serious obstacle in new gene evolution than the more commonly discussed evolutionary trade-offs between “old” and “new” functions of a gene, as it cannot be overcome by gene copy number changes. Further, we suggest a model for how RF2 autoregulation responds not only to alterations in the demand for RF2 activity, but also for RF1 activity.
  • Adler, Marlen, 1984-, et al. (författare)
  • High Fitness Costs and Instability of Gene Duplications Reduce Rates of Evolution of New Genes by Duplication-Divergence Mechanisms
  • 2014
  • Ingår i: Molecular biology and evolution. - 0737-4038 .- 1537-1719. ; 31:6, s. 1526-1535
  • Tidskriftsartikel (refereegranskat)abstract
    • An important mechanism for generation of new genes is by duplication-divergence of existing genes. Duplication-divergence includes several different sub-models, such as subfunctionalization where after accumulation of neutral mutations the original function is distributed between two partially functional and complementary genes, and neofunctionalization where a new function evolves in one of the duplicated copies while the old function is maintained in another copy. The likelihood of these mechanisms depends on the longevity of the duplicated state, which in turn depends on the fitness cost and genetic stability of the duplications. Here, we determined the fitness cost and stability of defined gene duplications/amplifications on a low copy number plasmid. Our experimental results show that the costs of carrying extra gene copies are substantial and that each additional kbp of DNA reduces fitness by approximately 0.15%. Furthermore, gene amplifications are highly unstable and rapidly segregate to lower copy numbers in absence of selection. Mathematical modelling shows that the fitness costs and instability strongly reduces the likelihood of both sub- and neofunctionalization, but that these effects can be off-set by positive selection for novel beneficial functions.
  • Adolfsson, Sofia, et al. (författare)
  • Lack of Dosage Compensation Accompanies the Arrested Stage of Sex Chromosome Evolution in Ostriches
  • 2013
  • Ingår i: Molecular biology and evolution. - 0737-4038 .- 1537-1719. ; 30:4, s. 806-810
  • Tidskriftsartikel (refereegranskat)abstract
    • Sex chromosome evolution is usually seen as a process that, once initiated, will inevitably progress toward an advanced stage of degeneration of the nonrecombining chromosome. However, despite evidence that avian sex chromosome evolution was initiated > 100 Ma, ratite birds have been trapped in an arrested stage of sex chromosome divergence. We performed RNA sequencing of several tissues from male and female ostriches and assembled the transcriptome de novo. A total of 315 Z-linked genes fell into two categories: those that have equal expression level in the two sexes (for which Z-W recombination still occurs) and those that have a 2-fold excess of male expression (for which Z-W recombination has ceased). We suggest that failure to evolve dosage compensation has constrained sex chromosome divergence in this basal avian lineage. Our results indicate that dosage compensation is a prerequisite for, not only a consequence of, sex chromosome evolution.
  • Ali, Raja Hashim, et al. (författare)
  • Identifying Clusters of High Confidence Homologies in Multiple Sequence Alignments
  • 2019
  • Ingår i: Molecular biology and evolution. - : OXFORD UNIV PRESS. - 0737-4038 .- 1537-1719. ; 36:10, s. 2340-2351
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple sequence alignment (MSA) is ubiquitous in evolution and bioinformatics. MSAs are usually taken to be a known and fixed quantity on which to perform downstream analysis despite extensive evidence that MSA accuracy and uncertainty affect results. These errors are known to cause a wide range of problems for downstream evolutionary inference, ranging from false inference of positive selection to long branch attraction artifacts. The most popular approach to dealing with this problem is to remove (filter) specific columns in the MSA that are thought to be prone to error. Although popular, this approach has had mixed success and several studies have even suggested that filtering might be detrimental to phylogenetic studies. We present a graph-based clustering method to address MSA uncertainty and error in the software Divvier (available at https://github.com/simonwhelan/Divvier), which uses a probabilistic model to identify clusters of characters that have strong statistical evidence of shared homology. These clusters can then be used to either filter characters from the MSA (partial filtering) or represent each of the clusters in a new column (divvying). We validate Divvier through its performance on real and simulated benchmarks, finding Divvier substantially outperforms existing filtering software by retaining more true pairwise homologies calls and removing more false positive pairwise homologies. We also find that Divvier, in contrast to other filtering tools, can alleviate long branch attraction artifacts induced by MSA and reduces the variation in tree estimates caused by MSA uncertainty.
  • Amiri, H., et al. (författare)
  • Proliferation and deterioration of Rickettsia palindromic elements
  • 2002
  • Ingår i: Molecular biology and evolution. - 0737-4038 .- 1537-1719. ; 19:8, s. 1234-1243
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been suggested that Rickettsia Palindromic Elements (RPEs) have evolved as selfish DNA that mediate protein sequence evolution by being targeted to genes that code for RNA and proteins. Here, we have examined the phylogenetic depth of two RPEs that are located close to the genes encoding elongation factors Tu (tuf) and G (fus) in Rickettsia. An exceptional organization of the elongation factor genes was found in all 11 species examined, with complete or partial RPEs identified downstream of the tuf gene (RPE-tuf) in six species and of the fus gene (RPE-fus) in 10 species. A phylogenetic reconstruction shows that both RPE-tuf and RPE-fus have evolved in a manner that is consistent with the expected species divergence. The analysis provides evidence for independent loss of RPE-tuf in several species, possibly mediated by short repetitive sequences flanking the site of excision. The remaining RPE-tuf sequences evolve as neutral sequences in different stages of deterioration. Likewise, highly fragmented remnants of the RPE-fus sequence were identified in two species. This suggests that genome-specific differences in the content of RPEs are the result of recent loss rather than recent proliferation.
  • Andersson, Jan O, et al. (författare)
  • Genome degradation is an ongoing process in Rickettsia
  • 1999
  • Ingår i: Molecular biology and evolution. - : SOC MOLECULAR BIOLOGY EVOLUTION. - 0737-4038 .- 1537-1719. ; 16:9, s. 1178-1191
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • To study reductive evolutionary processes in bacterial genomes, we examine sequences in the Rickettsia genomes which are unconstrained by selection and evolve as pseudogenes, one of which is the metK gene, which codes for AdoMet synthetase. Here, we sequenced the metK gene and three surrounding genes in eight different species of the genus Rickettsia. The metK gene was found to contain a high incidence of deletions in six lineages, while the three genes in its surroundings were functionally conserved in all eight lineages. A more drastic example of gene degradation was identified in the metK downstream region, which contained an open reading frame in Rickettsia felis. Remnants of this open reading frame could be reconstructed in five additional species by eliminating sites of frameshift mutations and termination codons. A detailed examination of the two reconstructed genes revealed that deletions strongly predominate over insertions and that there is a strong transition bias for point mutations which is coupled to an excess of GC-to-AT substitutions. Since the molecular evolution of these inactive genes should reflect the rates and patterns of neutral mutations, our results strongly suggest that there is a high spontaneous rate of deletions as well as a strong mutation bias toward AT pairs in the Rickettsia genomes. This may explain the low genomic G + C content (29%), the small genome size (1.1 Mb), and the high noncoding content (24%), as well as the presence of several pseudogenes in the Rickettsia prowazekii genome.
  • Andersson, Jan O, et al. (författare)
  • Pseudogenes, junk DNA, and the dynamics of Rickettsia genomes
  • 2001
  • Ingår i: Molecular biology and evolution. - 0737-4038 .- 1537-1719. ; 18:5, s. 829-839
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies of neutrally evolving sequences suggest that differences in eukaryotic genome sizes result from different rates of DNA loss. However, very few pseudogenes have been identified in microbial species, and the processes whereby genes and genomes deteriorate in bacteria remain largely unresolved. The typhus-causing agent, Rickettsia prowazekii, is exceptional in that as much as 24% of its 1.1-Mb genome consists of noncoding DNA and pseudogenes. To test the hypothesis that the noncoding DNA in the R. prowazekii genome represents degraded remnants of ancestral genes, we systematically examined all of the identified pseudogenes and their flanking sequences in three additional Rickettsia species. Consistent with the hypothesis, we observe sequence similarities between genes and pseudogenes in one species and intergenic DNA in another species. We show that the frequencies and average sizes of deletions are larger than insertions in neutrally evolving pseudogene sequences. Our results suggest that inactivated genetic material in the Rickettsia genomes deteriorates spontaneously due to a mutation bias for deletions and that the noncoding sequences represent DNA in the final stages of this degenerative process.
  • ANDRADE, S.C.S, et al. (författare)
  • A transcriptomic approach to ribbon worm systematics (Nemertea): resolving the Pilidiophora problem.
  • 2014
  • Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP): Molecular Biology and Evolution. - 0737-4038 .- 1537-1719. ; 31:12, s. 3206-3215
  • Tidskriftsartikel (refereegranskat)abstract
    • Resolving the deep relationships of ancient animal lineages has proven difficult using standard Sanger-sequencing approaches with a handful of markers. We thus reassess the relatively well-studied phylogeny of the phylum Nemertea (ribbon worms)—for which the targeted gene approaches had resolved many clades but had left key phylogenetic gaps—by using a phylogenomic approach using Illumina-based de novo assembled transcriptomes and automatic orthology prediction methods. The analysis of a concatenated data set of 2,779 genes (411,138 amino acids) with about 78% gene occupancy and a reduced version with 95% gene occupancy, under evolutionary models accounting or not for site-specific amino acid replacement patterns results in a well-supported phylogeny that recovers all major accepted nemertean clades with the monophyly of Heteronemertea, Hoplonemertea, Monostilifera, being well supported. Significantly, all the ambiguous patterns inferred from Sanger-based approaches were resolved, namely the monophyly of Palaeonemertea and Pilidiophora. By testing for possible conflict in the analyzed supermatrix, we observed that concatenation was the best solution, and the results of the analyses should settle prior debates on nemertean phylogeny. The study highlights the importance, feasibility, and completeness of Illumina-based phylogenomic data matrices.
  • Aswad, Amr, et al. (författare)
  • Evolutionary history of endogenous Human Herpesvirus 6 reflects human migration out of Africa
  • 2021
  • Ingår i: Molecular biology and evolution. - 0737-4038 .- 1537-1719. ; 38:1, s. 96-107
  • Tidskriftsartikel (refereegranskat)abstract
    • Human herpesvirus 6A and 6B (HHV-6) can integrate into the germline, and as a result about 70 million people harbour the genome of one of these viruses in every cell of their body. Until now, it has been largely unknown if i) these integrations are ancient, ii) if they still occur, and iii) whether circulating virus strains differ from integrated ones. Here we used next generation sequencing and mining of public human genome datasets to generate the largest and most diverse collection of circulating and integrated HHV-6 genomes studied to date. In genomes of geographically dispersed, only distantly-related people, we identified clades of integrated viruses that originated from a single ancestral event, confirming this with fluorescent in situ hybridization to directly observe the integration locus. In contrast to HHV-6B, circulating and integrated HHV-6A sequences form distinct clades, arguing against ongoing integration of circulating HHV-6A or "reactivation" of integrated HHV-6A. Taken together, our study provides the first comprehensive picture of the evolution of HHV-6, and reveals that integration of heritable HHV-6 has occurred since the time of, if not before, human migrations out of Africa.
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