scholarly journals Hypothesis: protein and RNA attributes are continuously optimized over time

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Sidney B. Cambridge

Abstract Background Little is known why proteins and RNAs exhibit half-lives varying over several magnitudes. Despite many efforts, a conclusive link between half-lives and gene function could not be established suggesting that other determinants may influence these molecular attributes. Results Here, I find that with increasing gene age there is a gradual and significant increase of protein and RNA half-lives, protein structure, and other molecular attributes that tend to affect protein abundance. These observations are accommodated in a hypothesis which posits that new genes at ‘birth’ are not optimized and thus their products exhibit low half-lives and less structure but continuous mutagenesis eventually improves these attributes. Thus, the protein and RNA products of the oldest genes obtained their high degrees of stability and structure only after billions of years while the products of younger genes had less time to be optimized and are therefore less stable and structured. Because more stable proteins with lower turnover require less transcription to maintain the same level of abundance, reduced transcription-associated mutagenesis (TAM) would fixate the changes by increasing gene conservation. Conclusions Consequently, the currently observed diversity of molecular attributes is a snapshot of gene products being at different stages along their temporal path of optimization.

PLoS ONE ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. e0238849
Author(s):  
Nora Palinkas-Bodzsar ◽  
Nikoletta Sztan ◽  
Tamas Molnar ◽  
Andras Hidas

Genetics ◽  
1990 ◽  
Vol 124 (2) ◽  
pp. 251-262 ◽  
Author(s):  
T Stearns ◽  
M A Hoyt ◽  
D Botstein

Abstract Three new genes affecting microtubule function in Saccharomyces cerevisiae were isolated by screening for mutants displaying supersensitivity to the antimicrotubule drug benomyl. Such mutants fall into six complementation groups: TUB1, TUB2 and TUB3, the three tubulin genes of yeast, and three new genes, which we have named CIN1, CIN2 and CIN4. Mutations in each of the CIN genes were also independently isolated by screening for mutants with increased rates of chromosome loss. Strains bearing mutations in the CIN genes are approximately tenfold more sensitive than wild type to both benomyl and to the related antimicrotubule drug, nocodazole. This phenotype is recessive for all alleles isolated. The CIN1, CIN2 and CIN4 genes were cloned by complementation of the benomyl-supersensitive phenotype. Null mutants of each of the genes are viable, and have phenotypes similar to those of the point mutants. Genetic evidence for the involvement of the CIN gene products in microtubule function comes from the observation that some tubulin mutations are suppressed by cin mutations, while other tubulin mutations are lethal in combination with cin mutations. Additional genetic experiments with cin mutants suggest that the three genes act together in the same pathway or structure to affect microtubule function.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S712-S712
Author(s):  
Christopher S Anderson ◽  
Yun Zhang ◽  
Anthony Corbett ◽  
Chin-Yi Chu ◽  
Lu Wang ◽  
...  

Abstract Background Respiratory Syncytial Virus (RSV) can be easily classified into two subtypes (A and B) based on the nucleic acid sequence of their genome. Phylogenic approaches have shown that within both subtypes separate lineages of viruses exist and new lineages continue to emerge. The role these genomic variations play in disease severity during RSV infection is largely unknown. Methods Next-generation viral RNA sequencing was performed on archived frozen nasal swabs of children infected with RSV in Rochester, NY between 1977-1998. Genomic variation was compared across year-of-isolation, age of host, and inpatient/outpatient status of host. Local RSV genomic variation was compared to variation of publicly available sequences isolated from hosts residing in other parts of the world. Results A and B subtypes demonstrated significant differences in the genetic sequence and primary-protein structure over time. G-protein was the most variable in both subtypes, but they differed in the number of unique genotypes detected. We found a significant association with disease severity (inpatient/outpatient status) and RSV phylogenetic topology, although the magnitude of the association differed by subtype. Variation in the primary protein structure of RSV viral proteins was also significantly associated with disease severity, but depended on which viral protein, and which subtype, was investigated. Lastly, local RSV genomic and protein-structure variation was similar to what was seen globally during this time period. Conclusion Overall, both subtypes demonstrated significant genetic change over time and these changes were associated with disease severity. These results suggest that the genetic variability of RSV may affect RSV disease in humans. Disclosures All Authors: No reported disclosures


Plants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1187
Author(s):  
Alexander A. Tyurin ◽  
Alexandra V. Suhorukova ◽  
Ksenia V. Kabardaeva ◽  
Irina V. Goldenkova-Pavlova

A large data array on plant gene expression accumulated thanks to comparative omic studies directs the efforts of researchers to the specific or fine effects of the target gene functions and, as a consequence, elaboration of relatively simple and concurrently effective approaches allowing for the insight into the physiological role of gene products. Numerous studies have convincingly demonstrated the efficacy of transient expression strategy for characterization of the plant gene functions. The review goals are (i) to consider the advantages and limitations of different plant systems and methods of transient expression used to find out the role of gene products; (ii) to summarize the current data on the use of the transient expression approaches for the insight into fine mechanisms underlying the gene function; and (iii) to outline the accomplishments in efficient transient expression of plant genes. In general, the review discusses the main and critical steps in each of the methods of transient gene expression in plants; areas of their application; main results obtained using plant objects; their contribution to our knowledge about the fine mechanisms of the plant gene functions underlying plant growth and development; and clarification of the mechanisms regulating complex metabolic pathways.


1998 ◽  
Vol 274 (3) ◽  
pp. H747-H751 ◽  
Author(s):  
Gary F. Mitchell ◽  
Andreas Jeron ◽  
Gideon Koren

Transgenic mouse models provided a powerful tool to evaluate the physiological significance of altered quantities or characteristics of specific gene products, such as cardiac ion channels. We have developed a system to record and analyze changes in the electrocardiogram in the mouse using an implantable telemetry system. The R-R and Q-T intervals were measured on individual beats and on signal-averaged complexes derived from 1, 2, or 4 s of contiguous data each hour during a 24-h period in three male and three female FVB mice. Duration of averaging had minimal effect on the measured Q-T. The Q-T interval was shown to be related to the square root of the R-R interval, and an appropriate formula for a rate-corrected Q-T interval (Q-Tc) was derived. Ketamine anesthesia was shown to markedly increase duration and variability in R-R, Q-T, and Q-Tc intervals. In conscious animals, variability in Q-T was low across animals and over time, suggesting that this should be a sensitive model for detection of changes in the Q-T interval in transgenic mice with ion channel defects.


2002 ◽  
Vol 184 (17) ◽  
pp. 4672-4680 ◽  
Author(s):  
Mian Cai ◽  
Luying Xun

ABSTRACT The first three enzymes of the pentachlorophenol (PCP) degradation pathway in Sphingobium chlorophenolicum (formerly Sphingomonas chlorophenolica) ATCC 39723 have been characterized, and the corresponding genes, pcpA, pcpB, and pcpC, have been individually cloned and sequenced. To search for new genes involved in PCP degradation and map the physical locations of the pcp genes, a 24-kb fragment containing pcpA and pcpC was completely sequenced. A putative LysR-type transcriptional regulator gene, pcpM, and a maleylacetate reductase gene, pcpE, were identified upstream of pcpA. pcpE was found to play a role in PCP degradation. pcpB was not found on the 24-kb fragment. The four gene products PcpB, PcpC, PcpA, and PcpE were responsible for the metabolism of PCP to 3-oxoadipate in ATCC 39723, and inactivational mutation of each gene disrupted the degradation pathway. The organization of the pcp genes is unusual because the four PCP-degrading genes, pcpA, pcpB, pcpC, and pcpE, were found to be located at four discrete locations. Two hypothetical LysR-type regulator genes, pcpM and pcpR, have been identified; pcpM was not required, but pcpR was essential for the induction of pcpB, pcpA, and pcpE. The coinducers of PcpR were PCP and other polychlorinated phenols. The expression of pcpC was constitutive. Thus, the organization and regulation of the genes involved in PCP degradation to 3-oxoadipate were documented.


2012 ◽  
Vol 195-196 ◽  
pp. 391-396
Author(s):  
Xi Chen ◽  
Hao Jiang ◽  
Wai Ki Ching ◽  
Li Min Li

Protein 3D structure is one of the main factors in reecting gene functions. The availability of protein structure data in Protein Data Bank (PDB) allows us to conduct gene function analysis based on protein structure data. However, the molecules in PDB, whose structures having been determined, are always not corresponding to a unique gene. That is to say, the mapping from a gene to the PDB is not one-to-one. This feature complicates the situation and increases the difculty of gene function analysis. In this paper, we attempt to tackle this problem and also study the problem of predicting gene function from protein structures based on the gene-PDB mapping. We rst obtain the gene-PDB mapping, which is used to represent a gene by the structure set of all its corresponding PDB molecules. We then dene a new gene-gene similarity measurement based on the structure similarity between PDB molecules, and we further show that this new measurement matches with the gene functional similarity. This means that the measurement we dened here can be used effectively for gene function prediction.


2020 ◽  
Author(s):  
Yi-Bo Tong ◽  
Meng-Wei Shi ◽  
Sheng Hu Qian ◽  
Yu-Jie Chen ◽  
Zhi-Hui Luo ◽  
...  

ABSTRACTThe origination of new genes contributes to the biological diversity of life. New genes may quickly build their own network in the genomes, exert important functions, and generate novel phenotypes. Dating gene age and inferring the origination mechanisms of new genes, like primate-specific gene, is the basis for the functional study of the genes. However, no comprehensive resource of gene age estimates across species is available. Here, we systematically dated the age of 9,102,113 protein-coding genes from 565 species in the Ensembl and Ensembl Genomes databases, including 82 bacteria, 57 protists, 134 fungi, 58 plants, 56 metazoa, and 178 vertebrates, using protein-family-based pipeline with Wagner parsimony algorithm. We also collected gene age estimate data from other studies and uniformed the gene age estimates to time ranges in million years for comparison across studies. All the data were cataloged into GenOrigin (http://genorigin.chenzxlab.cn/), a userfriendly new database of gene age estimates, where users can browse gene age estimates by species, age and gene ontology. In GenOrigin, the information such as gene age estimates, annotation, gene ontology, ortholog and paralog, as well as detailed gene presence/absence views for gene age inference based on the species tree with evolutionary timescale, was provided to researchers for exploring gene functions.


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