scholarly journals Genes encoding teleost orthologs of human haplo-insufficient and monoallelic genes remain in duplicate more frequently than the whole genome

2021 ◽  
Author(s):  
Floriane Picolo ◽  
Anna Grandchamp ◽  
Benoît Piégu ◽  
Reiner A. Veitia ◽  
Philippe Monget
Keyword(s):  
X Chromosome ◽  
Evolutionary Biology ◽  
Gene Dosage ◽  
Whole Genome ◽  
Teleost Species ◽  
Human Genomes ◽  
Human Genes ◽  
Genes Encoding ◽  
Parental Imprinting ◽  
Dosage Balance

AbstractGene dosage is important is an important issue both in cell and evolutionary biology. Most genes are present in two copies in eukaryotic cells. The first outstanding exception is monoallelic gene expression (MA) that concerns genes localized on the X chromosome or in regions undergoing parental imprinting in eutherians, and many other genes scattered throughout the genome. The second exception concerns haploinsufficiency (HI), responsible for the fact that a single functional copy of a gene in a diploid organism is insufficient to ensure a normal biological function. One of the most important mechanisms ensuring functional innovation during evolution is Whole genome duplication (WGD). In addition to the two WGDs that have occurred in vertebrate genomes, the teleost genomes underwent an additional WGD, after their divergence from tetrapod. In the present work, we have studied on 57 teleost species whether the orthologs of human MA or HI genes remain more frequently in duplicates or returned more frequently in singleton than the rest of the genome. Our results show that the teleost orthologs of HI human genes remained more frequently in duplicate than the rest of the genome in all the teleost species studied. No signal was observed for the orthologs of genes localized on the human X chromosome or subjected to parental imprinting. Surprisingly, the teleost orthologs of the other human MA genes remained in duplicate more frequently than the rest of the genome for most teleost species. These results suggest that the teleost orthologs of MA and HI human genes also undergo selective pressures either related to absolute protein amounts and/or of dosage balance issues. However, these constraints seem to be different for MA genes in teleost in comparison with human genomes.

scholarly journals Genes Encoding Teleost Orthologs of Human Haploinsufficient and Monoallelically Expressed Genes Remain in Duplicate More Frequently Than the Whole Genome

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Floriane Picolo ◽  
Anna Grandchamp ◽  
Benoît Piégu ◽  
Antoine D. Rolland ◽  
Reiner A. Veitia ◽  
...  
Keyword(s):  
X Chromosome ◽  
Evolutionary Biology ◽  
Gene Dosage ◽  
Whole Genome ◽  
Teleost Species ◽  
Human Genomes ◽  
Human Genes ◽  
Genes Encoding ◽  
Parental Imprinting ◽  
Dosage Balance

Gene dosage is an important issue both in cell and evolutionary biology. Most genes are present in two copies or alleles in diploid eukariotic cells. The most outstanding exception is monoallelic gene expression (MA) that concerns genes localized on the X chromosome or in regions undergoing parental imprinting in eutherians, and many other genes scattered throughout the genome. In diploids, haploinsufficiency (HI) implies that a single functional copy of a gene in a diploid organism is insufficient to ensure a normal biological function. One of the most important mechanisms ensuring functional innovation during evolution is whole genome duplication (WGD). In addition to the two WGDs that have occurred in vertebrate genomes, the teleost genomes underwent an additional WGD, after their divergence from tetrapods. In the present work, we have studied on 57 teleost species whether the orthologs of human MA or HI genes remain more frequently in duplicates or returned more frequently in singleton than the rest of the genome. Our results show that the teleost orthologs of HI human genes remained more frequently in duplicate than the rest of the genome in all of the teleost species studied. No signal was observed for the orthologs of genes mapping to the human X chromosome or subjected to parental imprinting. Surprisingly, the teleost orthologs of the other human MA genes remained in duplicate more frequently than the rest of the genome for most teleost species. These results suggest that the teleost orthologs of MA and HI human genes also undergo selective pressures either related to absolute protein amounts and/or of dosage balance issues. However, these constraints seem to be different for MA genes in teleost in comparison with human genomes.

scholarly journals Grass MicroRNA Gene Paleohistory Unveils New Insights into Gene Dosage Balance in Subgenome Partitioning after Whole-Genome Duplication

2012 ◽  
Vol 24 (5) ◽  
pp. 1776-1792 ◽  
Author(s):  
Michael Abrouk ◽  
Rongzhi Zhang ◽  
Florent Murat ◽  
Aili Li ◽  
Caroline Pont ◽  
...  
Keyword(s):  
Whole Genome Duplication ◽  
Genome Duplication ◽  
Gene Dosage ◽  
Whole Genome ◽  
Microrna Gene ◽  
Dosage Balance

scholarly journals Expanding the Atlas of Functional Missense Variation for Human Genes

2017 ◽  
Author(s):  
Jochen Weile ◽  
Song Sun ◽  
Atina G. Cote ◽  
Jennifer Knapp ◽  
Marta Verby ◽  
...  
Keyword(s):  
Human Disease ◽  
Disease Genes ◽  
Functional Variation ◽  
Human Genomes ◽  
Pathogenic Variation ◽  
Human Genes ◽  
Genes Encoding ◽  
Missense Variation ◽  
Thiamin Pyrophosphokinase ◽  
Human Disease Genes

AbstractAlthough we now routinely sequence human genomes, we can confidently identify only a fraction of the sequence variants that have a functional impact. Here we developed a deep mutational scanning framework that produces exhaustive maps for human missense variants by combining random codon-mutagenesis and multiplexed functional variation assays with computational imputation and refinement. We applied this framework to four proteins corresponding to six human genes: UBE2I (encoding SUMO E2 conjugase), SUMO1 (small ubiquitin-like modifier), TPK1 (thiamin pyrophosphokinase), and CALM1/2/3 (three genes encoding the protein calmodulin). The resulting maps recapitulate known protein features, and confidently identify pathogenic variation. Assays potentially amenable to deep mutational scanning are already available for 57% of human disease genes, suggesting that DMS could ultimately map functional variation for all human disease genes.

Identification of microsatellite markers near the human genes encoding the beta-cell ATP-sensitive K+ channel and linkage studies with NIDDM in Japanese

Diabetes ◽  
1996 ◽  
Vol 45 (2) ◽  
pp. 267-269 ◽  
Author(s):  
N. Iwasaki ◽  
M. Kawamura ◽  
K. Yamagata ◽  
N. J. Cox ◽  
S. Karibe ◽  
...  
Keyword(s):  
Beta Cell ◽  
Microsatellite Markers ◽  
K Channel ◽  
Linkage Studies ◽  
Human Genes ◽  
Genes Encoding

scholarly journals Structures and chromosomal localizations of two human genes encoding synaptobrevins 1 and 2.

1990 ◽  
Vol 265 (28) ◽  
pp. 17267-17273 ◽  
Author(s):  
B T Archer ◽  
T Ozçelik ◽  
R Jahn ◽  
U Francke ◽  
T C Südhof
Keyword(s):  
Human Genes ◽  
Genes Encoding

scholarly journals Molecular characterization of clinical carbapenem-resistant Enterobacterales from Qatar

2021 ◽  
Author(s):  
Fatma Ben Abid ◽  
Clement K. M. Tsui ◽  
Yohei Doi ◽  
Anand Deshmukh ◽  
Christi L. McElheny ◽  
...  
Keyword(s):  
Common Species ◽  
Clinical Samples ◽  
Whole Genome ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Genes Encoding ◽  
Encoding Genes ◽  
Sequence Types ◽  
Common Sequence

AbstractOne hundred forty-nine carbapenem-resistant Enterobacterales from clinical samples obtained between April 2014 and November 2017 were subjected to whole genome sequencing and multi-locus sequence typing. Klebsiella pneumoniae (81, 54.4%) and Escherichia coli (38, 25.5%) were the most common species. Genes encoding metallo-β-lactamases were detected in 68 (45.8%) isolates, and OXA-48-like enzymes in 60 (40.3%). blaNDM-1 (45; 30.2%) and blaOXA-48 (29; 19.5%) were the most frequent. KPC-encoding genes were identified in 5 (3.6%) isolates. Most common sequence types were E. coli ST410 (8; 21.1%) and ST38 (7; 18.4%), and K. pneumoniae ST147 (13; 16%) and ST231 (7; 8.6%).

scholarly journals A study of transposable element-associated structural variations (TASVs) using a de novo-assembled Korean genome

2021 ◽  
Author(s):  
Seyoung Mun ◽  
Songmi Kim ◽  
Wooseok Lee ◽  
Keunsoo Kang ◽  
Thomas J. Meyer ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Genome Assembly ◽  
De Novo ◽  
Personal Genome ◽  
Human Populations ◽  
Whole Genome ◽  
Structural Variations ◽  
Insert Size ◽  
Human Genomes ◽  
Next Generation Sequencing Ngs

AbstractAdvances in next-generation sequencing (NGS) technology have made personal genome sequencing possible, and indeed, many individual human genomes have now been sequenced. Comparisons of these individual genomes have revealed substantial genomic differences between human populations as well as between individuals from closely related ethnic groups. Transposable elements (TEs) are known to be one of the major sources of these variations and act through various mechanisms, including de novo insertion, insertion-mediated deletion, and TE–TE recombination-mediated deletion. In this study, we carried out de novo whole-genome sequencing of one Korean individual (KPGP9) via multiple insert-size libraries. The de novo whole-genome assembly resulted in 31,305 scaffolds with a scaffold N50 size of 13.23 Mb. Furthermore, through computational data analysis and experimental verification, we revealed that 182 TE-associated structural variation (TASV) insertions and 89 TASV deletions contributed 64,232 bp in sequence gain and 82,772 bp in sequence loss, respectively, in the KPGP9 genome relative to the hg19 reference genome. We also verified structural differences associated with TASVs by comparative analysis with TASVs in recent genomes (AK1 and TCGA genomes) and reported their details. Here, we constructed a new Korean de novo whole-genome assembly and provide the first study, to our knowledge, focused on the identification of TASVs in an individual Korean genome. Our findings again highlight the role of TEs as a major driver of structural variations in human individual genomes.

scholarly journals Comparative regulomics supports pervasive selection on gene dosage following whole genome duplication

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Gareth B. Gillard ◽  
Lars Grønvold ◽  
Line L. Røsæg ◽  
Matilde Mengkrog Holen ◽  
Øystein Monsen ◽  
...  
Keyword(s):  
Genome Evolution ◽  
Whole Genome Duplication ◽  
Genome Stability ◽  
Genome Duplication ◽  
Gene Dosage ◽  
Whole Genome ◽  
Specific Expression ◽  
Tissue Specific ◽  
Genome Doubling ◽  
Expression Evolution

Abstract Background Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap, we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80–100 million years ago. Results We find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Ohnolog expression levels have evolved mostly asymmetrically, by diverting one ohnolog copy down a path towards lower expression and possible pseudogenization. Loss of expression in one ohnolog is significantly associated with transposable element insertions in promoters and likely driven by selection on gene dosage including selection on stoichiometric balance. We also find symmetric expression shifts, and these are associated with genes under strong evolutionary constraints such as ribosome subunit genes. This possibly reflects selection operating to achieve a gene dose reduction while avoiding accumulation of “toxic mutations”. Mechanistically, ohnolog regulatory divergence is dictated by the number of bound transcription factors in promoters, with transposable elements being one likely source of novel binding sites driving tissue-specific gains in expression. Conclusions Our results imply pervasive adaptive expression evolution following WGD to overcome the immediate challenges posed by genome doubling and to exploit the long-term genetic opportunities for novel phenotype evolution.

scholarly journals Escape from X Chromosome Inactivation and the Female Predominance in Autoimmune Diseases

2021 ◽  
Vol 22 (3) ◽  
pp. 1114
Author(s):  
Ali Youness ◽  
Charles-Henry Miquel ◽  
Jean-Charles Guéry
Keyword(s):  
Autoimmune Diseases ◽  
X Chromosome ◽  
Gene Dosage ◽  
X Chromosome Inactivation ◽  
Chromosome Inactivation ◽  
X Chromosomes ◽  
Female Sex Hormones ◽  
Inactive X Chromosome ◽  
Immune Related Genes ◽  
Female Specific

Women represent 80% of people affected by autoimmune diseases. Although, many studies have demonstrated a role for sex hormone receptor signaling, particularly estrogens, in the direct regulation of innate and adaptive components of the immune system, recent data suggest that female sex hormones are not the only cause of the female predisposition to autoimmunity. Besides sex steroid hormones, growing evidence points towards the role of X-linked genetic factors. In female mammals, one of the two X chromosomes is randomly inactivated during embryonic development, resulting in a cellular mosaicism, where about one-half of the cells in a given tissue express either the maternal X chromosome or the paternal one. X chromosome inactivation (XCI) is however not complete and 15 to 23% of genes from the inactive X chromosome (Xi) escape XCI, thereby contributing to the emergence of a female-specific heterogeneous population of cells with bi-allelic expression of some X-linked genes. Although the direct contribution of this genetic mechanism in the female susceptibility to autoimmunity still remains to be established, the cellular mosaicism resulting from XCI escape is likely to create a unique functional plasticity within female immune cells. Here, we review recent findings identifying key immune related genes that escape XCI and the relationship between gene dosage imbalance and functional responsiveness in female cells.

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