scholarly journals Phylostratic Shift of Whole-Genome Duplications in Normal Mammalian Tissues towards Unicellularity Is Driven by Developmental Bivalent Genes and Reveals a Link to Cancer

2020 ◽  
Vol 21 (22) ◽  
pp. 8759 ◽  
Author(s):  
Olga V. Anatskaya ◽  
Alexander E. Vinogradov ◽  
Ninel M. Vainshelbaum ◽  
Alessandro Giuliani ◽  
Jekaterina Erenpreisa
Keyword(s):  
Metastatic Cancer ◽  
Principal Component ◽  
Viral Origin ◽  
Whole Genome Duplications ◽  
Mouse Tissues ◽  
Protein Interactome ◽  
Mammalian Tissues ◽  
Genome Duplications ◽  
Transcriptome Comparison ◽  
Phenotypic Shift

Tumours were recently revealed to undergo a phylostratic and phenotypic shift to unicellularity. As well, aggressive tumours are characterized by an increased proportion of polyploid cells. In order to investigate a possible shared causation of these two features, we performed a comparative phylostratigraphic analysis of ploidy-related genes, obtained from transcriptomic data for polyploid and diploid human and mouse tissues using pairwise cross-species transcriptome comparison and principal component analysis. Our results indicate that polyploidy shifts the evolutionary age balance of the expressed genes from the late metazoan phylostrata towards the upregulation of unicellular and early metazoan phylostrata. The up-regulation of unicellular metabolic and drug-resistance pathways and the downregulation of pathways related to circadian clock were identified. This evolutionary shift was associated with the enrichment of ploidy with bivalent genes (p < 10−16). The protein interactome of activated bivalent genes revealed the increase of the connectivity of unicellulars and (early) multicellulars, while circadian regulators were depressed. The mutual polyploidy-c-MYC-bivalent genes-associated protein network was organized by gene-hubs engaged in both embryonic development and metastatic cancer including driver (proto)-oncogenes of viral origin. Our data suggest that, in cancer, the atavistic shift goes hand-in-hand with polyploidy and is driven by epigenetic mechanisms impinging on development-related bivalent genes.

scholarly journals Coregulation of tandem duplicate genes slows evolution of subfunctionalization in mammals

2015 ◽  
Author(s):  
Xun Lan ◽  
Jonathan K. Pritchard
Keyword(s):  
Gene Expression ◽  
Gene Dosage ◽  
Functional Adaptation ◽  
Small Scale ◽  
Loss Of Function ◽  
Whole Genome Duplications ◽  
Mouse Tissues ◽  
Genome Duplications ◽  
Key Factor

AbstractGene duplication is a fundamental process in genome evolution. However, most young duplicates are degraded into pseudogenes by loss-of-function mutations, and the factors that allow some duplicate pairs to survive long-term remain controversial. One class of models to explain duplicate retention invokes sub- or neofunctionalization, especially through evolution of gene expression, while other models focus on sharing of gene dosage. While studies of whole genome duplications tend to support dosage sharing, the primary mechanisms in mammals–where duplications are small-scale and thus disrupt dosage balance– are unclear. Using RNA-seq data from 46 human and 26 mouse tissues we find that sub-functionalization of expression evolves slowly, and is rare among duplicates that arose within the placental mammals. A major impediment to subfunctionalization is that tandem duplicates tend to be co-regulated by shared genomic elements, in contrast to the standard assumption of modularity of gene expression. Instead, consistent with the dosage-sharing hypothesis, most young duplicates are down-regulated to match expression of outgroup singleton genes. Our data suggest that dosage sharing of expression is a key factor in the initial survival of mammalian duplicates, followed by slower functional adaptation enabling long-term preservation.

scholarly journals Molecular Phylogenetic Analysis of the AIG Family in Vertebrates

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1190
Author(s):  
Yuqi Huang ◽  
Minghao Sun ◽  
Lenan Zhuang ◽  
Jin He
Keyword(s):  
Phylogenetic Analysis ◽  
Gene Family ◽  
Functional Characterization ◽  
Vertebrate Evolution ◽  
Molecular Phylogenetic Analysis ◽  
Whole Genome Duplications ◽  
Genome Duplications ◽  
Molecular Phylogenetic ◽  
Duplication Events ◽  
Inducible Genes

Androgen-inducible genes (AIGs), which can be regulated by androgen level, constitute a group of genes characterized by the presence of the AIG/FAR-17a domain in its protein sequence. Previous studies on AIGs demonstrated that one member of the gene family, AIG1, is involved in many biological processes in cancer cell lines and that ADTRP is associated with cardiovascular diseases. It has been shown that the numbers of AIG paralogs in humans, mice, and zebrafish are 2, 2, and 3, respectively, indicating possible gene duplication events during vertebrate evolution. Therefore, classifying subgroups of AIGs and identifying the homologs of each AIG member are important to characterize this novel gene family further. In this study, vertebrate AIGs were phylogenetically grouped into three major clades, ADTRP, AIG1, and AIG-L, with AIG-L also evident in an outgroup consisting of invertebrsate species. In this case, AIG-L, as the ancestral AIG, gave rise to ADTRP and AIG1 after two rounds of whole-genome duplications during vertebrate evolution. Then, the AIG family, which was exposed to purifying forces during evolution, lost or gained some of its members in some species. For example, in eutherians, Neognathae, and Percomorphaceae, AIG-L was lost; in contrast, Salmonidae and Cyprinidae acquired additional AIG copies. In conclusion, this study provides a comprehensive molecular phylogenetic analysis of vertebrate AIGs, which can be employed for future functional characterization of AIGs.

scholarly journals Comprehensive characterization of 536 patient-derived xenograft models prioritizes candidates for targeted treatment

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hua Sun ◽  
Song Cao ◽  
R. Jay Mashl ◽  
Chia-Kuei Mo ◽  
Simone Zaccaria ◽  
...  
Keyword(s):  
Human Tumors ◽  
Multiple Time ◽  
Cancer Treatments ◽  
Whole Genome Duplications ◽  
Patient Derived Xenograft ◽  
Genome Duplications ◽  
Genomic Characterization ◽  
Cancer Types ◽  
Multiple Time Points ◽  
Pdx Models

AbstractDevelopment of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs’ recapitulation of human tumors.

scholarly journals Chromosome Distribution of Highly Conserved Tandemly Arranged Repetitive DNAs in the Siberian Sturgeon (Acipenser baerii)

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1375
Author(s):  
Larisa S. Biltueva ◽  
Dmitry Yu. Prokopov ◽  
Svetlana A. Romanenko ◽  
Elena A. Interesova ◽  
Manfred Schartl ◽  
...  
Keyword(s):  
Duplication Event ◽  
Siberian Sturgeon ◽  
Genome Duplication Event ◽  
Acipenser Baerii ◽  
Whole Genome Duplications ◽  
Sturgeon Species ◽  
Genome Duplications ◽  
Size Groups ◽  
Genomic Studies ◽  
Syntenic Regions

Polyploid genomes present a challenge for cytogenetic and genomic studies, due to the high number of similar size chromosomes and the simultaneous presence of hardly distinguishable paralogous elements. The karyotype of the Siberian sturgeon (Acipenser baerii) contains around 250 chromosomes and is remarkable for the presence of paralogs from two rounds of whole-genome duplications (WGD). In this study, we applied the sterlet-derived acipenserid satDNA-based whole chromosome-specific probes to analyze the Siberian sturgeon karyotype. We demonstrate that the last genome duplication event in the Siberian sturgeon was accompanied by the simultaneous expansion of several repetitive DNA families. Some of the repetitive probes serve as good cytogenetic markers distinguishing paralogous chromosomes and detecting ancestral syntenic regions, which underwent fusions and fissions. The tendency of minisatellite specificity for chromosome size groups previously observed in the sterlet genome is also visible in the Siberian sturgeon. We provide an initial physical chromosome map of the Siberian sturgeon genome supported by molecular markers. The application of these data will facilitate genomic studies in other recent polyploid sturgeon species.

scholarly journals On the Expansion of “Dangerous” Gene Repertoires by Whole-Genome Duplications in Early Vertebrates

Cell Reports ◽  
2012 ◽  
Vol 2 (5) ◽  
pp. 1387-1398 ◽  
Author(s):  
Param Priya Singh ◽  
Séverine Affeldt ◽  
Ilaria Cascone ◽  
Rasim Selimoglu ◽  
Jacques Camonis ◽  
...  
Keyword(s):  
Whole Genome ◽  
Whole Genome Duplications ◽  
Genome Duplications ◽  
Early Vertebrates

scholarly journals Legume Cytosolic and Plastid Acetyl-Coenzyme—A Carboxylase Genes Differ by Evolutionary Patterns and Selection Pressure Schemes Acting before and after Whole-Genome Duplications

Genes ◽  
2018 ◽  
Vol 9 (11) ◽  
pp. 563 ◽  
Author(s):  
Anna Szczepaniak ◽  
Michał Książkiewicz ◽  
Jan Podkowiński ◽  
Katarzyna Czyż ◽  
Marek Figlerowicz ◽  
...  
Keyword(s):  
Selection Pressure ◽  
Coenzyme A ◽  
Phylogenetic Inference ◽  
Whole Genome ◽  
Evolutionary Patterns ◽  
Acetyl Coenzyme A ◽  
Acetyl Coenzyme ◽  
Whole Genome Duplications ◽  
Genome Duplications ◽  
Acetyl Coenzyme A Carboxylase

Acetyl-coenzyme A carboxylase (ACCase, E.C.6.4.1.2) catalyzes acetyl-coenzyme A carboxylation to malonyl coenzyme A. Plants possess two distinct ACCases differing by cellular compartment and function. Plastid ACCase contributes to de novo fatty acid synthesis, whereas cytosolic enzyme to the synthesis of very long chain fatty acids, phytoalexins, flavonoids, and anthocyanins. The narrow leafed lupin (Lupinus angustifolius L.) represents legumes, a plant family which evolved by whole-genome duplications (WGDs). The study aimed on the contribution of these WGDs to the multiplication of ACCase genes and their further evolutionary patterns. The molecular approach involved bacterial artificial chromosome (BAC) library screening, fluorescent in situ hybridization, linkage mapping, and BAC sequencing. In silico analysis encompassed sequence annotation, comparative mapping, selection pressure calculation, phylogenetic inference, and gene expression profiling. Among sequenced legumes, the highest number of ACCase genes was identified in lupin and soybean. The most abundant plastid ACCase subunit genes were accB. ACCase genes in legumes evolved by WGDs, evidenced by shared synteny and Bayesian phylogenetic inference. Transcriptional activity of almost all copies was confirmed. Gene duplicates were conserved by strong purifying selection, however, positive selection occurred in Arachis (accB2) and Lupinus (accC) lineages, putatively predating the WGD event(s). Early duplicated accA and accB genes underwent transcriptional sub-functionalization.

scholarly journals Improved Understanding of the Role of Gene and Genome Duplications in Chordate Evolution With New Genome and Transcriptome Sequences

2021 ◽  
Vol 9 ◽  
Author(s):  
Madeleine E. Aase-Remedios ◽  
David E. K. Ferrier
Keyword(s):  
Chromosomal Rearrangements ◽  
Expression Patterns ◽  
Gene Families ◽  
Evolutionary Transitions ◽  
Whole Genome Duplications ◽  
Chordate Evolution ◽  
Genome Duplications ◽  
The Many ◽  
Genome Assemblies ◽  
The Impact

Comparative approaches to understanding chordate genomes have uncovered a significant role for gene duplications, including whole genome duplications (WGDs), giving rise to and expanding gene families. In developmental biology, gene families created and expanded by both tandem and WGDs are paramount. These genes, often involved in transcription and signalling, are candidates for underpinning major evolutionary transitions because they are particularly prone to retention and subfunctionalisation, neofunctionalisation, or specialisation following duplication. Under the subfunctionalisation model, duplication lays the foundation for the diversification of paralogues, especially in the context of gene regulation. Tandemly duplicated paralogues reside in the same regulatory environment, which may constrain them and result in a gene cluster with closely linked but subtly different expression patterns and functions. Ohnologues (WGD paralogues) often diversify by partitioning their expression domains between retained paralogues, amidst the many changes in the genome during rediploidisation, including chromosomal rearrangements and extensive gene losses. The patterns of these retentions and losses are still not fully understood, nor is the full extent of the impact of gene duplication on chordate evolution. The growing number of sequencing projects, genomic resources, transcriptomics, and improvements to genome assemblies for diverse chordates from non-model and under-sampled lineages like the coelacanth, as well as key lineages, such as amphioxus and lamprey, has allowed more informative comparisons within developmental gene families as well as revealing the extent of conserved synteny across whole genomes. This influx of data provides the tools necessary for phylogenetically informed comparative genomics, which will bring us closer to understanding the evolution of chordate body plan diversity and the changes underpinning the origin and diversification of vertebrates.

Sign in / Sign up

Export Citation Format

Share Document