scholarly journals Identification of two evolutionarily conserved genes regulating processing of engulfed apoptotic cells

Nature ◽  
2010 ◽  
Vol 464 (7289) ◽  
pp. 778-782 ◽  
Author(s):  
Jason M. Kinchen ◽  
Kodi S. Ravichandran
Keyword(s):  
Apoptotic Cells ◽  
Evolutionarily Conserved ◽  
Conserved Genes

scholarly journals An Evolutionarily Conserved Pathway Essential for Orsay Virus Infection of Caenorhabditis elegans

mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Hongbing Jiang ◽  
Kevin Chen ◽  
Luis E. Sandoval ◽  
Christian Leung ◽  
David Wang
Keyword(s):  
Caenorhabditis Elegans ◽  
Virus Infection ◽  
Tyrosine Kinase ◽  
Model Organism ◽  
Wiskott Aldrich Syndrome ◽  
C Elegans ◽  
Evolutionarily Conserved ◽  
Conserved Genes ◽  
Orsay Virus ◽  
Syndrome Protein

ABSTRACT Many fundamental biological discoveries have been made in Caenorhabditis elegans. The discovery of Orsay virus has enabled studies of host-virus interactions in this model organism. To identify host factors critical for Orsay virus infection, we designed a forward genetic screen that utilizes a virally induced green fluorescent protein (GFP) reporter. Following chemical mutagenesis, two Viro (virus induced reporter off) mutants that failed to express GFP were mapped to sid-3, a nonreceptor tyrosine kinase, and B0280.13 (renamed viro-2), an ortholog of human Wiskott-Aldrich syndrome protein (WASP). Both mutants yielded Orsay virus RNA levels comparable to that of the residual input virus, suggesting that they are not permissive for Orsay virus replication. In addition, we demonstrated that both genes affect an early prereplication stage of Orsay virus infection. Furthermore, it is known that the human ortholog of SID-3, activated CDC42-associated kinase (ACK1/TNK2), is capable of phosphorylating human WASP, suggesting that VIRO-2 may be a substrate for SID-3 in C. elegans. A targeted RNA interference (RNAi) knockdown screen further identified the C. elegans gene nck-1, which has a human ortholog that interacts with TNK2 and WASP, as required for Orsay virus infection. Thus, genetic screening in C. elegans identified critical roles in virus infection for evolutionarily conserved genes in a known human pathway. IMPORTANCE Orsay virus is the only known virus capable of naturally infecting the model organism Caenorhabditis elegans, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of C. elegans to identify three host genes, sid-3, viro-2, and nck-1, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection. IMPORTANCE Orsay virus is the only known virus capable of naturally infecting the model organism Caenorhabditis elegans, which shares many evolutionarily conserved genes with humans. We exploited the robust genetic tractability of C. elegans to identify three host genes, sid-3, viro-2, and nck-1, which are essential for Orsay virus infection. Mutant animals that lack these three genes are highly defective in viral replication. Strikingly, the human orthologs of these three genes, activated CDC42-associated kinase (TNK2), Wiskott-Aldrich syndrome protein (WASP), and noncatalytic region of tyrosine kinase adaptor protein 1 (NCK1) are part of a known signaling pathway in mammals. These results suggest that TNK2, WASP, and NCK1 may play important roles in mammalian virus infection.

scholarly journals Cross-species hybridizations on a multi-species cDNA microarray to identify evolutionarily conserved genes expressed in oocytes

BMC Genomics ◽  
2006 ◽  
Vol 7 (1) ◽  
Author(s):  
Maud Vallée ◽  
Claude Robert ◽  
Steve Méthot ◽  
Marie-France Palin ◽  
Marc-André Sirard
Keyword(s):  
Cdna Microarray ◽  
Evolutionarily Conserved ◽  
Conserved Genes

scholarly journals SUMO modification in apoptosis

2020 ◽  
Vol 52 (1) ◽  
pp. 1-10
Author(s):  
Peiyao Li ◽  
Huiru Jing ◽  
Yanzhe Wang ◽  
Lei Yuan ◽  
Hui Xiao ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Neurodegenerative Diseases ◽  
Growth And Development ◽  
Recent Progress ◽  
Biological Process ◽  
Regulatory Mechanisms ◽  
Apoptotic Cells ◽  
Post Translational Modification ◽  
Sumo Modification ◽  
Evolutionarily Conserved

AbstractApoptosis and clearance of dead cells is highly evolutionarily conserved from nematode to humans, which is crucial to the growth and development of multicellular organism. Fail to remove apoptotic cells often lead to homeostasis imbalance, fatal autoimmune diseases, and neurodegenerative diseases. Small ubiquitin-related modifiers (SUMOs) modification is a post-translational modification of ubiquitin proteins mediated by the sentrin-specific proteases (SENPs) family. SUMO modification is widely involved in many cellular biological process, and abnormal SUMO modification is also closely related to many major human diseases. Recent researches have revealed that SUMO modification event occurs during apoptosis and clearance of apoptotic cells, and plays an important role in the regulation of apoptotic signaling pathways. This review summarizes some recent progress in the revelation of regulatory mechanisms of these pathways and provides some potential researching hotpots of the SUMO modification regulation to apoptosis.

scholarly journals Capturing Evolutionary Signatures in Transcriptomes with myTAI

2016 ◽  
Author(s):  
Hajk-Georg Drost ◽  
Alexander Gabel ◽  
Tomislav Domazet-Lošo ◽  
Marcel Quint ◽  
Ivo Grosse
Keyword(s):  
Open Source Software ◽  
Biological Process ◽  
Wide Spectrum ◽  
Sequence Divergence ◽  
Evolutionary Information ◽  
Evolutionary Constraints ◽  
Evolutionarily Conserved ◽  
Conserved Genes ◽  
Transcriptomic Level ◽  
Developmental Hourglass

AbstractCombining transcriptome data of biological processes or response to stimuli with evolutionary information such as the phylogenetic conservation of genes or their sequence divergence rates enables the investigation of evolutionary constraints on these processes or responses. Such phylotranscriptomic analyses recently unraveled that mid-developmental transcriptomes of fly, fish, and cress were dominated by evolutionarily conserved genes and genes under negative selection and thus recapitulated the developmental hourglass on the transcriptomic level. Here, we present a protocol for performing phylotranscriptomic analyses on any biological process of interest. When applying this protocol, users are capable of detecting different evolutionary constraints acting on different stages of the biological process of interest in any species. For each step of the protocol, modular and easy-to-use open-source software tools are provided, which enable a broad range of scientists to apply phylotranscriptomic analyses to a wide spectrum of biological questions.

scholarly journals Genetic Basis of Increased Lifespan and Postponed Senescence in Drosophila melanogaster

2020 ◽  
Vol 10 (3) ◽  
pp. 1087-1098
Author(s):  
Grace A. Parker ◽  
Nathan Kohn ◽  
Ally Spirina ◽  
Anna McMillen ◽  
Wen Huang ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Basis ◽  
Natural Populations ◽  
Life History Trait ◽  
Reproductive Senescence ◽  
Evolutionary Forces ◽  
Human Orthologs ◽  
Evolutionarily Conserved ◽  
Conserved Genes ◽  
B Lines

Limited lifespan and senescence are near-universal phenomena. These quantitative traits exhibit variation in natural populations due to the segregation of many interacting loci and from environmental effects. Due to the complexity of the genetic control of lifespan and senescence, our understanding of the genetic basis of variation in these traits is incomplete. Here, we analyzed the pattern of genetic divergence between long-lived (O) Drosophila melanogaster lines selected for postponed reproductive senescence and unselected control (B) lines. We quantified the productivity of the O and B lines and found that reproductive senescence is maternally controlled. We therefore chose 57 candidate genes that are expressed in ovaries, 49 of which have human orthologs, and assessed the effects of RNA interference in ovaries and accessary glands on lifespan and reproduction. All but one candidate gene affected at least one life history trait in one sex or productivity week. In addition, 23 genes had antagonistic pleiotropic effects on lifespan and productivity. Identifying evolutionarily conserved genes affecting increased lifespan and delayed reproductive senescence is the first step toward understanding the evolutionary forces that maintain segregating variation at these loci in nature and may provide potential targets for therapeutic intervention to delay senescence while increasing lifespan.

Genetic variation in mRNA coding sequences of highly conserved genes

2001 ◽  
Vol 5 (3) ◽  
pp. 113-118 ◽  
Author(s):  
ANNELOOR L. M. A. TEN ASBROEK ◽  
JEFFREY OLSEN ◽  
DAVID HOUSMAN ◽  
FRANK BAAS ◽  
VINCE STANTON
Keyword(s):  
Disease Genes ◽  
Protein Coding ◽  
Coding Sequences ◽  
Human Genes ◽  
Evolutionarily Conserved ◽  
Conserved Genes ◽  
The Difference ◽  
Minimum Estimate ◽  
Human Disease Genes ◽  
Evolutionary Comparisons

The frequency and distribution of genetic polymorphism in the human genome is a question of major importance. We have studied this in highly conserved genes, which encode crucial functions such as DNA replication, mRNA transcription, and translation. Evolutionary comparisons suggest that these genes are under particularly strong selective pressure, and their frequency of nucleotide sequence polymorphism would be expected to represent a minimum estimate for sequence variation throughout the genome. We have analyzed the complete coding sequence and the 3′-untranslated region (3′-UTR) of 22 human genes, most of which have homologs in all cellular organisms and all of which are at least 25% amino acid identical to homologs in yeast. Comparisons with similar studies of less conserved human disease genes indicate that 1) evolutionarily conserved genes are, on average, less polymorphic than disease related genes; 2) the difference in polymorphism levels is attributable almost entirely to reduced levels of variation in protein coding sequences, whereas noncoding sequences have similar levels of polymorphism; and 3) the character of polymorphism, in terms of the spectrum and frequency of mutational changes, is similar.

scholarly journals Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants

2015 ◽  
Vol 112 (3) ◽  
pp. E277-E286 ◽  
Author(s):  
Ankita Bansal ◽  
Lihua J. Zhu ◽  
Kelvin Yen ◽  
Heidi A. Tissenbaum
Keyword(s):  
Caenorhabditis Elegans ◽  
Growth Factor ◽  
Protein Translation ◽  
Wild Type ◽  
Aging Research ◽  
Future Studies ◽  
Mitochondrial Signaling ◽  
Evolutionarily Conserved ◽  
Conserved Genes ◽  
Better Than

Aging research has been very successful at identifying signaling pathways and evolutionarily conserved genes that extend lifespan with the assumption that an increase in lifespan will also increase healthspan. However, it is largely unknown whether we are extending the healthy time of life or simply prolonging a period of frailty with increased incidence of age-associated diseases. Here we use Caenorhabditis elegans, one of the premiere systems for lifespan studies, to determine whether lifespan and healthspan are intrinsically correlated. We conducted multiple cellular and organismal assays on wild type as well as four long-lived mutants (insulin/insulin-like growth factor-1, dietary restriction, protein translation, mitochondrial signaling) in a longitudinal manner to determine the health of the animals as they age. We find that some long-lived mutants performed better than wild type when measured chronologically (number of days). However, all long-lived mutants increased the proportion of time spent in a frail state. Together, these data suggest that lifespan can no longer be the sole parameter of interest and reveal the importance of evaluating multiple healthspan parameters for future studies on antiaging interventions.

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