Recent CIG publications Archive

 BMC Genomics. 2020 Nov 18;21(Suppl 10):779. doi: 10.1186/s12864-020-07011-0.

A generalized Robinson-Foulds distance for labeled trees

Samuel Briand ¹, Christophe Dessimoz ^{2 3 4 5 6}, Nadia El-Mabrouk ⁷, Manuel Lafond ⁸, Gabriela Lobinska ⁹

Abstract

Background: The Robinson-Foulds (RF) distance is a well-established measure between phylogenetic trees. Despite a lack of biological justification, it has the advantages of being a proper metric and being computable in linear time. For phylogenetic applications involving genes, however, a crucial aspect of the trees ignored by the RF metric is the type of the branching event (e.g. speciation, duplication, transfer, etc).

Results: We extend RF to trees with labeled internal nodes by including a node flip operation, alongside edge contractions and extensions. We explore properties of this extended RF distance in the case of a binary labeling. In particular, we show that contrary to the unlabeled case, an optimal edit path may require contracting “good” edges, i.e. edges shared between the two trees.

Conclusions: We provide a 2-approximation algorithm which is shown to perform well empirically. Looking ahead, computing distances between labeled trees opens up a variety of new algorithmic directions.Implementation and simulations available at https://github.com/DessimozLab/pylabeledrf .

Keywords: Edit distance; Labeled trees; Robinson-Foulds; Tree metric.

• PMID: 33208096
• PMCID: PMC7677779
• DOI: 10.1186/s12864-020-07011-0

Nutrients. 2020 Nov 12;12(11):E3476. doi: 10.3390/nu12113476.

Peroxisome Proliferator-Activated Receptors as Molecular Links between Caloric Restriction and Circadian Rhythm

Kalina Duszka ¹, Walter Wahli ^2 3 4

Abstract

The circadian rhythm plays a chief role in the adaptation of all bodily processes to internal and environmental changes on the daily basis. Next to light/dark phases, feeding patterns constitute the most essential element entraining daily oscillations, and therefore, timely and appropriate restrictive diets have a great capacity to restore the circadian rhythm. One of the restrictive nutritional approaches, caloric restriction (CR) achieves stunning results in extending health span and life span via coordinated changes in multiple biological functions from the molecular, cellular, to the whole-body levels. The main molecular pathways affected by CR include mTOR, insulin signaling, AMPK, and sirtuins. Members of the family of nuclear receptors, the three peroxisome proliferator-activated receptors (PPARs), PPARα, PPARβ/δ, and PPARγ take part in the modulation of these pathways. In this non-systematic review, we describe the molecular interconnection between circadian rhythm, CR-associated pathways, and PPARs. Further, we identify a link between circadian rhythm and the outcomes of CR on the whole-body level including oxidative stress, inflammation, and aging. Since PPARs contribute to many changes triggered by CR, we discuss the potential involvement of PPARs in bridging CR and circadian rhythm.

Keywords: caloric restriction; circadian rhythm; metabolism; nuclear receptors.

• PMID: 33198317
• DOI: 10.3390/nu12113476

Trends Genet. 2020 Nov 14;S0168-9525(20)30297-3. doi: 10.1016/j.tig.2020.10.008. Online ahead of print.

Anything but Ordinary – Emerging Splicing Mechanisms in Eukaryotic Gene Regulation

Niels H Gehring ¹, Jean-Yves Roignant ²Affiliations expand

Abstract

Splicing of precursor mRNAs (pre-mRNA) is an important step during eukaryotic gene expression. The identification of the actual splice sites and the proper removal of introns are essential for the production of the desired mRNA isoforms and their encoded proteins. While the basic mechanisms of splicing regulation are well understood, recent work has uncovered a growing number of noncanonical splicing mechanisms that play key roles in the regulation of gene expression. In this review, we summarize the current principles of splicing regulation, including the impact of cis and trans regulatory elements, as well as the influence of chromatin structure, transcription, and RNA modifications. We further discuss the recent development of emerging splicing mechanisms, such as recursive and back splicing, and their impact on gene expression.

Keywords: RNA modifications; RNA-binding protein; circular RNA; cotranscriptional splicing; pre-mRNA splicing; recursive splicing.

• PMID: 33203572
• DOI: 10.1016/j.tig.2020.10.008

Nature. 2020 Nov 11. doi: 10.1038/s41586-020-2899-z. Online ahead of print.

Transcriptome and translatome co-evolution in mammals

Zhong-Yi Wang ¹, Evgeny Leushkin ², Angélica Liechti ³, Svetlana Ovchinnikova ¹, Katharina Mößinger ¹, Thoomke Brüning ¹, Coralie Rummel ³, Frank Grützner ⁴, Margarida Cardoso-Moreira ¹, Peggy Janich ³, David Gatfield ³, Boubou Diagouraga ^5 6, Bernard de Massy ⁵, Mark E Gill ⁷, Antoine H F M Peters ^7 8, Simon Anders ¹, Henrik Kaessmann ⁹

Affiliations expand

Abstract

Gene-expression programs define shared and species-specific phenotypes, but their evolution remains largely uncharacterized beyond the transcriptome layer¹. Here we report an analysis of the co-evolution of translatomes and transcriptomes using ribosome-profiling and matched RNA-sequencing data for three organs (brain, liver and testis) in five mammals (human, macaque, mouse, opossum and platypus) and a bird (chicken). Our within-species analyses reveal that translational regulation is widespread in the different organs, in particular across the spermatogenic cell types of the testis. The between-species divergence in gene expression is around 20% lower at the translatome layer than at the transcriptome layer owing to extensive buffering between the expression layers, which especially preserved old, essential and housekeeping genes. Translational upregulation specifically counterbalanced global dosage reductions during the evolution of sex chromosomes and the effects of meiotic sex-chromosome inactivation during spermatogenesis. Despite the overall prevalence of buffering, some genes evolved faster at the translatome layer-potentially indicating adaptive changes in expression; testis tissue shows the highest fraction of such genes. Further analyses incorporating mass spectrometry proteomics data establish that the co-evolution of transcriptomes and translatomes is reflected at the proteome layer. Together, our work uncovers co-evolutionary patterns and associated selective forces across the expression layers, and provides a resource for understanding their interplay in mammalian organs.

• PMID: 33177713
• DOI: 10.1038/s41586-020-2899-z

Nucleic Acids Res. 2020 Nov 11;gkaa1007. doi: 10.1093/nar/gkaa1007. Online ahead of print.

OMA orthology in 2021: website overhaul, conserved isoforms, ancestral gene order and more

Adrian M Altenhoff ^1 2, Clément-Marie Train ³, Kimberly J Gilbert ^1 3 4, Ishita Mediratta ^3 5, Tarcisio Mendes de Farias ¹, David Moi ^1 3 4, Yannis Nevers ^1 3 4, Hale-Seda Radoykova ^6 7, Victor Rossier ^1 3 4, Alex Warwick Vesztrocy ^1 3 4, Natasha M Glover ^1 3 4, Christophe Dessimoz ^{1 3 4 6 7}
Affiliations expand

Abstract

OMA is an established resource to elucidate evolutionary relationships among genes from currently 2326 genomes covering all domains of life. OMA provides pairwise and groupwise orthologs, functional annotations, local and global gene order conservation (synteny) information, among many other functions. This update paper describes the reorganisation of the database into gene-, group- and genome-centric pages. Other new and improved features are detailed, such as reporting of the evolutionarily best conserved isoforms of alternatively spliced genes, the inferred local order of ancestral genes, phylogenetic profiling, better cross-references, fast genome mapping, semantic data sharing via RDF, as well as a special coronavirus OMA with 119 viruses from the Nidovirales order, including SARS-CoV-2, the agent of the COVID-19 pandemic. We conclude with improvements to the documentation of the resource through primers, tutorials and short videos. OMA is accessible at https://omabrowser.org.

© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.

• PMID: 33174605
• DOI: 10.1093/nar/gkaa1007

J med. genet. 2020 Nov 10;jmedgenet-2020-107015. doi: 10.1136/jmedgenet-2020-107015. Online ahead of print.

Inhibition of G-protein signalling in cardiac dysfunction of intellectual developmental disorder with cardiac arrhythmia (IDDCA) syndrome

Pasquelena De Nittis ¹, Stephanie Efthymiou ², Alexandre Sarre ³, Nicolas Guex ⁴, Jacqueline Chrast ¹, Audrey Putoux ⁵, Tipu Sultan ⁶, Javeria Raza Alvi ⁶, Zia Ur Rahman ⁶, Faisal Zafar ⁷, Nuzhat Rana ⁷, Fatima Rahman ⁸, Najwa Anwar ⁸, Shazia Maqbool ⁸, Maha S Zaki ⁹, Joseph G Gleeson ¹⁰, David Murphy ², Hamid Galehdari ¹¹, Gholamreza Shariati ¹², Neda Mazaheri ¹¹, Alireza Sedaghat ¹³, SYNAPS Study Group; Gaetan Lesca ¹⁴, Nicolas Chatron ^1 14, Vincenzo Salpietro ², Marilena Christoforou ², Henry Houlden ², William F Simonds ¹⁵, Thierry Pedrazzini ¹⁶, Reza Maroofian ², Alexandre Reymond ¹⁷
Collaborators, Affiliations expand

Abstract

Background: Pathogenic variants of GNB5 encoding the β₅ subunit of the guanine nucleotide-binding protein cause IDDCA syndrome, an autosomal recessive neurodevelopmental disorder associated with cognitive disability and cardiac arrhythmia, particularly severe bradycardia.

Methods: We used echocardiography and telemetric ECG recordings to investigate consequences of Gnb5 loss in mouse.

Results: We delineated a key role of Gnb5 in heart sinus conduction and showed that Gnb5-inhibitory signalling is essential for parasympathetic control of heart rate (HR) and maintenance of the sympathovagal balance. Gnb5^-/- mice were smaller and had a smaller heart than Gnb5^+/+ and Gnb5^+/- , but exhibited better cardiac function. Lower autonomic nervous system modulation through diminished parasympathetic control and greater sympathetic regulation resulted in a higher baseline HR in Gnb5^-/- mice. In contrast, Gnb5^-/- mice exhibited profound bradycardia on treatment with carbachol, while sympathetic modulation of the cardiac stimulation was not altered. Concordantly, transcriptome study pinpointed altered expression of genes involved in cardiac muscle contractility in atria and ventricles of knocked-out mice. Homozygous Gnb5 loss resulted in significantly higher frequencies of sinus arrhythmias. Moreover, we described 13 affected individuals, increasing the IDDCA cohort to 44 patients.

Conclusions: Our data demonstrate that loss of negative regulation of the inhibitory G-protein signalling causes HR perturbations in Gnb5^– /- mice, an effect mainly driven by impaired parasympathetic activity. We anticipate that unravelling the mechanism of Gnb5 signalling in the autonomic control of the heart will pave the way for future drug screening.

Keywords: GNB5variants; Gnb5-null mouse models; IDDCA; cardiac conduction anomalies.

• PMID: 33172956
• DOI: 10.1136/jmedgenet-2020-107015