Coregulation of tandem duplicate genes slows evolution of subfunctionalization in mammals

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms21228759 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8759 ◽

Cited By ~ 2

Author(s):

Olga V. Anatskaya ◽

Alexander E. Vinogradov ◽

Ninel M. Vainshelbaum ◽

Alessandro Giuliani ◽

Jekaterina Erenpreisa

Keyword(s):

Metastatic Cancer ◽

Principal Component ◽

Viral Origin ◽

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.

Cause and consequences of genome duplication in haploid yeast populations

10.1101/247320 ◽

2018 ◽

Cited By ~ 2

Author(s):

Kaitlin J. Fisher ◽

Sean W. Buskirk ◽

Ryan C. Vignogna ◽

Daniel A. Marad ◽

Gregory I. Lang

Keyword(s):

Genome Duplication ◽

Neutral Evolution ◽

Phenotypic Evolution ◽

Deleterious Mutations ◽

Structural Variants ◽

Laboratory Evolution ◽

Fitness Advantage ◽

ABSTRACTWhole genome duplications (WGD) represent important evolutionary events that shape future adaptation. WGDs are known to have occurred in the lineages leading to plants, fungi, and vertebrates. Changes to ploidy level impact the rate and spectrum of beneficial mutations and thus the rate of adaptation. Laboratory evolution experiments initiated with haploid Saccharomyces cerevisiae cultures repeatedly experience WGD. We report recurrent genome duplication in 46 haploid yeast populations evolved for 4,000 generations. We find that WGD confers a fitness advantage, and this immediate fitness gain is accompanied by a shift in genomic and phenotypic evolution. The presence of ploidy-enriched targets of selection and structural variants reveals that autodiploids utilize adaptive paths inaccessible to haploids. We find that autodiploids accumulate recessive deleterious mutations, indicating an increased capacity for neutral evolution. Finally, we report that WGD results in a reduced adaptation rate, indicating a trade-off between immediate fitness gains and long term adaptability.

Region-specific expression of young small-scale duplications in the human central nervous system

10.21203/rs.3.rs-130244/v1 ◽

2020 ◽

Author(s):

Solène Brohard ◽

Vincent Frouin ◽

Vincent Meyer ◽

Smahane Chalabi ◽

Jean-François Deleuze ◽

...

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

Brain Evolution ◽

Tissue Expression ◽

Small Scale ◽

Human Central Nervous System ◽

Specific Expression ◽

Regional Specialization ◽

Abstract Background: The duplication of genes is one of the main genetic mechanisms that led to the gain in complexity of biological tissue. Although the implication of duplicated gene expression in brain evolution was extensively studied through comparisons between organs, their role in the regional specialization of the adult human central nervous system has not yet been well described. Results: Our work explored intra-organ expression properties of paralogs through multiple territories of the human central nervous system (CNS) using transcriptome data generated by the Genotype-Tissue Expression (GTEx) consortium. Interestingly, we found that paralogs were associated with region-specific expression in CNS, suggesting their involvement in the differentiation of these territories. Beside the influence of gene expression level on region-specificity, we observed the contribution of both duplication age and duplication type to the CNS region-specificity of paralogs. Indeed, we found that small scale duplicated genes (SSDs) and in particular ySSDs ( SSDs younger than the 2 rounds of whole genome duplications ) were more CNS region-specific than other paralogs. Next, by studying the two paralogs of ySSD pairs, we observed that when they were region-specific, they tend to be specific to the same region more often than for other paralogs, showing the high co-expression of ySSD pairs. Extension of this analysis to families of paralogs showed that the families with co-expressed gene members (i.e. homogeneous families) were enriched in ySSDs. Furthermore, these homogeneous families tended to be region-specific families, where the majority of their gene members were specifically expressed in the same region. Conclusions: Overall, our study suggests the major involvement of ySSDs in the differentiation of human central nervous system territories. Therefore, we show the relevance of exploring region-specific expression of paralogs at the intra-organ level.

Tangled up in two: a burst of genome duplications at the end of the Cretaceous and the consequences for plant evolution

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2013.0353 ◽

2014 ◽

Vol 369 (1648) ◽

pp. 20130353 ◽

Cited By ~ 90

Author(s):

Kevin Vanneste ◽

Steven Maere ◽

Yves Van de Peer

Keyword(s):

Large Scale ◽

Plant Evolution ◽

Small Scale ◽

Whole Genome ◽

Polyploid Species ◽

Plant Genomes ◽

Genome Duplications ◽

Duplication Events ◽

Biological Innovations

Genome sequencing has demonstrated that besides frequent small-scale duplications, large-scale duplication events such as whole genome duplications (WGDs) are found on many branches of the evolutionary tree of life. Especially in the plant lineage, there is evidence for recurrent WGDs, and the ancestor of all angiosperms was in fact most likely a polyploid species. The number of WGDs found in sequenced plant genomes allows us to investigate questions about the roles of WGDs that were hitherto impossible to address. An intriguing observation is that many plant WGDs seem associated with periods of increased environmental stress and/or fluctuations, a trend that is evident for both present-day polyploids and palaeopolyploids formed around the Cretaceous–Palaeogene (K–Pg) extinction at 66 Ma. Here, we revisit the WGDs in plants that mark the K–Pg boundary, and discuss some specific examples of biological innovations and/or diversifications that may be linked to these WGDs. We review evidence for the processes that could have contributed to increased polyploid establishment at the K–Pg boundary, and discuss the implications on subsequent plant evolution in the Cenozoic.

Region-specific expression of young small-scale duplications in the human central nervous system

BMC Ecology and Evolution ◽

10.1186/s12862-021-01794-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Solène Brohard-Julien ◽

Vincent Frouin ◽

Vincent Meyer ◽

Smahane Chalabi ◽

Jean-François Deleuze ◽

...

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

Brain Evolution ◽

Tissue Expression ◽

Small Scale ◽

Human Central Nervous System ◽

Specific Expression ◽

Regional Specialization ◽

Abstract Background The duplication of genes is one of the main genetic mechanisms that led to the gain in complexity of biological tissue. Although the implication of duplicated gene expression in brain evolution was extensively studied through comparisons between organs, their role in the regional specialization of the adult human central nervous system has not yet been well described. Results Our work explored intra-organ expression properties of paralogs through multiple territories of the human central nervous system (CNS) using transcriptome data generated by the Genotype-Tissue Expression (GTEx) consortium. Interestingly, we found that paralogs were associated with region-specific expression in CNS, suggesting their involvement in the differentiation of these territories. Beside the influence of gene expression level on region-specificity, we observed the contribution of both duplication age and duplication type to the CNS region-specificity of paralogs. Indeed, we found that small scale duplicated genes (SSDs) and in particular ySSDs (SSDs younger than the 2 rounds of whole genome duplications) were more CNS region-specific than other paralogs. Next, by studying the two paralogs of ySSD pairs, we observed that when they were region-specific, they tend to be specific to the same region more often than for other paralogs, showing the high co-expression of ySSD pairs. The extension of this analysis to families of paralogs showed that the families with co-expressed gene members (i.e. homogeneous families) were enriched in ySSDs. Furthermore, these homogeneous families tended to be region-specific families, where the majority of their gene members were specifically expressed in the same region. Conclusions Overall, our study suggests the involvement of ySSDs in the differentiation of human central nervous system territories. Therefore, we show the relevance of exploring region-specific expression of paralogs at the intra-organ level.

MicroRNA-129-5p Inhibited C2C12 Myogenesis and Repressed Slow Fiber Gene Expression in vitro

AJP Cell Physiology ◽

10.1152/ajpcell.00578.2020 ◽

2021 ◽

Author(s):

Ying Peng ◽

Meixue Xu ◽

Mingle Dou ◽

Xin'E Shi ◽

Gongshe Yang ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Myogenic Differentiation ◽

C2c12 Cell ◽

Negative Regulator ◽

C2c12 Cells ◽

Loss Of Function ◽

Mouse Tissues ◽

Slow Fiber ◽

Fiber Gene

The miR-129 family is widely reported as tumor repressors, while, their roles in skeletal muscle have not been fully investigated. Here, the function and mechanism of miR-129-5p in skeletal muscle, a member of the miR-129 family, were explored using C2C12 cell line. Our study shown that miR-129-5p was widely detected in mouse tissues, with the highest expression in skeletal muscle. Gain- and loss-of-function study shown that miR-129-5p could negatively regulate myogenic differentiation, indicated by reduced ratio of MyHC-positive myofibers and repressed expression of myogenic genes, such as MyoD, MyoG and MyHC. Furthermore, miR-129-5p was more enriched in fast extensor digitalis lateralis (EDL) than in slow soleus (SOL). Enhanced miR-129-5p could significantly reduce the expression of mitochondrial cox family, together with that of MyHC I, and knockdown of miR-129-5p conversely increased the expression of cox genes and MyHC I. Mechanistically, miR-129-5p directly targeted the 3'-UTR of Mef2a, which was suppressed by miR-129-5p agomir at both mRNA and protein levels in C2C12 cells. Moreover, overexpression of Mef2a could rescue the inhibitory effects of miR-129-5p on the expression of myogenic factors and MyHC I. Collectively, our data revealed that miR-129-5p as a negative regulator of myogenic differentiation and slow fiber gene expression, thus affecting body metabolic homeostasis.

Of numbers and movement – understanding transcription factor pathogenesis by advanced microscopy

Disease Models & Mechanisms ◽

10.1242/dmm.046516 ◽

2020 ◽

Vol 13 (12) ◽

pp. dmm046516

Author(s):

Julia M. T. Auer ◽

Jack J. Stoddart ◽

Ioannis Christodoulou ◽

Ana Lima ◽

Kassiani Skouloudaki ◽

...

Keyword(s):

Gene Expression ◽

Single Molecule ◽

Molecular Mechanisms ◽

Gene Dosage ◽

Super Resolution ◽

Loss Of Function ◽

Developmental Defects ◽

Tf Gene

ABSTRACTTranscription factors (TFs) are life-sustaining and, therefore, the subject of intensive research. By regulating gene expression, TFs control a plethora of developmental and physiological processes, and their abnormal function commonly leads to various developmental defects and diseases in humans. Normal TF function often depends on gene dosage, which can be altered by copy-number variation or loss-of-function mutations. This explains why TF haploinsufficiency (HI) can lead to disease. Since aberrant TF numbers frequently result in pathogenic abnormalities of gene expression, quantitative analyses of TFs are a priority in the field. In vitro single-molecule methodologies have significantly aided the identification of links between TF gene dosage and transcriptional outcomes. Additionally, advances in quantitative microscopy have contributed mechanistic insights into normal and aberrant TF function. However, to understand TF biology, TF-chromatin interactions must be characterised in vivo, in a tissue-specific manner and in the context of both normal and altered TF numbers. Here, we summarise the advanced microscopy methodologies most frequently used to link TF abundance to function and dissect the molecular mechanisms underlying TF HIs. Increased application of advanced single-molecule and super-resolution microscopy modalities will improve our understanding of how TF HIs drive disease.

Gene expression shapes the patterns of parallel evolution of herbicide resistance in the agricultural weedMonochoria vaginalis

10.1101/2021.03.10.434542 ◽

2021 ◽

Author(s):

Shinji Tanigaki ◽

Akira Uchino ◽

Shigenori Okawa ◽

Chikako Miura ◽

Kenshiro Hamamura ◽

...

Keyword(s):

Gene Expression ◽

Herbicide Resistance ◽

Parallel Evolution ◽

Acetolactate Synthase ◽

Duplicate Gene ◽

Target Site ◽

Loss Of Function ◽

Functional Characterisation ◽

Gene Copies ◽

Key Factor

AbstractThe evolution of herbicide resistance in weeds is an example of parallel evolution, through which genes encoding herbicide target proteins are repeatedly represented as evolutionary loci. The number of herbicide target-site genes differs among species, and little is known regarding the effects of duplicate gene copies on the evolution of herbicide resistance. We investigated the evolution of herbicide resistance inMonochoria vaginalis, which carries five copies of sulfonylurea target-site acetolactate synthase (ALS) genes. Suspected resistant populations collected across Japan were investigated for herbicide sensitivity andALSgene sequences, followed by functional characterisation andALSgene expression analysis. We identified over 60 resistant populations, all of which carried resistance-conferring amino acid substitutions exclusively inMvALS1orMvALS3. AllMvALS4alleles carried a loss-of-function mutation. Although the enzymatic properties of ALS encoded by these genes were not markedly different, the expression ofMvALS1andMvALS3was prominently higher among allALSgenes. The higher expression ofMvALS1andMvALS3is the driving force of the biased representation of genes during the evolution of herbicide resistance inM. vaginalis. Our findings highlight that gene expression is a key factor in creating evolutionary hotspots.

Region-specific expression of young small-scale duplications in the human central nervous system

10.1101/821256 ◽

2019 ◽

Author(s):

Solène Brohard-Julien ◽

Vincent Frouin ◽

Vincent Meyer ◽

Smahane Chalabi ◽

Jean-François Deleuze ◽

...

Keyword(s):

Gene Expression ◽

Central Nervous System ◽

Nervous System ◽

Brain Evolution ◽

Tissue Expression ◽

Small Scale ◽

Human Central Nervous System ◽

Specific Expression ◽

Regional Specialization ◽

ABSTRACTBackgroundThe duplication of genes is one of the main genetic mechanisms that led to the gain in complexity of biological tissue. Although the implication of duplicated gene expression in brain evolution was extensively studied through comparisons between organs, their role in the regional specialization of the adult human central nervous system has not yet been well described.ResultsOur work explored intra-organ expression properties of paralogs through multiple territories of the human central nervous system (CNS) using transcriptome data generated by the Genotype-Tissue Expression (GTEx) consortium. Interestingly, we found that paralogs were associated with region-specific expression in CNS, suggesting their involvement in the differentiation of these territories. Beside the influence of gene expression level on region-specificity, we observed the contribution of both duplication age and duplication type to the CNS region-specificity of paralogs. Indeed, we found that small scale duplicated genes (SSDs) and in particular ySSDs (SSDs younger than the 2 rounds of whole genome duplications) were more CNS region-specific than other paralogs. Next, by studying the two paralogs of ySSD pairs, we observed that when they were region-specific, they tend to be specific to the same region more often than for other paralogs, showing the high co-expression of ySSD pairs. Extension of this analysis to families of paralogs showed that the families with co-expressed gene members (i.e. homogeneous families) were enriched in ySSDs. Furthermore, these homogeneous families tended to be region-specific families, where the majority of their gene members were specifically expressed in the same region.ConclusionsOverall, our study suggests the major involvement of ySSDs in the differentiation of human central nervous system territories. Therefore, we show the relevance of exploring region-specific expression of paralogs at the intra-organ level.

Attachment of oral bacteria to titanium surfaces: An SEM study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100170074 ◽

1994 ◽

Vol 52 ◽

pp. 468-469

Author(s):

J. E. Laffoon ◽

R. L. Anderson ◽

J. C. Keller ◽

C. D. Wu-Yuan

Keyword(s):

Technical Problem ◽

Titanium Implant ◽

Oral Bacteria ◽

Bacterial Cells ◽

Thin Sections ◽

Surface Ultrastructure ◽

Sem Study ◽

Key Factor ◽

Titanium Surfaces

Titanium (Ti) dental implants have been used widely for many years. Long term implant failures are related, in part, to the development of peri-implantitis frequently associated with bacteria. Bacterial adherence and colonization have been considered a key factor in the pathogenesis of many biomaterial based infections. Without the initial attachment of oral bacteria to Ti-implant surfaces, subsequent polymicrobial accumulation and colonization leading to peri-implant disease cannot occur. The overall goal of this study is to examine the implant-oral bacterial interfaces and gain a greater understanding of their attachment characteristics and mechanisms. Since the detailed cell surface ultrastructure involved in attachment is only discernible at the electron microscopy level, the study is complicated by the technical problem of obtaining titanium implant and attached bacterial cells in the same ultra-thin sections. In this study, a technique was developed to facilitate the study of Ti implant-bacteria interface.Discs of polymerized Spurr’s resin (12 mm x 5 mm) were formed to a thickness of approximately 3 mm using an EM block holder (Fig. 1). Titanium was then deposited by vacuum deposition to a film thickness of 300Å (Fig. 2).