Научная статья на тему 'Destabilizing selection against under-expression of human immunostimulatory and immunosuppressive genes both provokes and prevents rheumatoid arthritis, correspondingly, as a self-domestication syndrome'

Destabilizing selection against under-expression of human immunostimulatory and immunosuppressive genes both provokes and prevents rheumatoid arthritis, correspondingly, as a self-domestication syndrome Текст научной статьи по специальности «Биологические науки»

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Текст научной работы на тему «Destabilizing selection against under-expression of human immunostimulatory and immunosuppressive genes both provokes and prevents rheumatoid arthritis, correspondingly, as a self-domestication syndrome»

sels and leaf mesophyll on the permeability of these tissues and on microclimatic parameters around the leaf.

The adequacy of the model parameters selected as a result of testing is discussed.

This work was supported by Russian Science Foundation (grant No 19-74-10037).

Modeling the influence of the availability of NAD+ for the SIRT1 enzyme on the interaction of the circadian

oscillator with the inflammatory response system to bacterial infection

N. L. Podkolodnyy1,2, N. N. Tverdokhleb1, O. A. Podkolodnaya1

1The Federal Research Center Institute of Cytology and Genetics SB RAS

2Institute of Computational Mathematics and Mathematical Geophysics SB RAS

Email: pnl@bionet.nsc.ru

DOI 10.24412/cl-35065-2021-1-02-54

A mathematical model of the influence of the availability of NAD + for the SIRT1 enzyme on the interac-

tion of the circadian oscillator with the inflammatory response system to bacterial infection has been devel-

oped and verified on experimental data. To verify the model, we used data on the daily dynamics of gene ex-

pression in the liver of wild-type mice and with knockouts of circadian genes, information on biologically justi-

fied intervals of parameter values, etc. Sensitivity analysis for the parameters of the oscillation period and

the amplitude of the change in the main variables of the model made it possible to identify the important pa-

rameters.

Modeling showed a pronounced circadian character of changes in Sirt1 and NFkB activity, and made it

possible to assess age-related changes in the functioning of the circadian oscillator, the NAD + consuming en-

zymes, and the level of NF-kB activation induced by LPS.

Thus, the developed model makes it possible to predict diurnal and age-related changes in the activity of

the inflammatory response to bacterial infection through NF-kB, and the results of modeling serve as a justifi-

cation for a chronotherapeutic approach in the treatment of inflammatory diseases.

This work was supported by the grants No 0259-2021-0009 and �0315-2021-0005 from the Russian Government

Budget.

Destabilizing selection against under-expression of human immunostimulatory and immunosuppressive

genes both provokes and prevents rheumatoid arthritis, correspondingly, as a self-domestication syndrome

M. P. Ponomarenko1, E. A. Oshchepkova1, I. V. Chadaeva1, D. Yu. Oshchepkov1, V. A. Kozlov2

1Institute of Cytology and Genetics SB RAS

2Research Institute of Fundamental and Clinical Immunology SB RAS

Email: pon@bionet.nsc.ru

DOI 10.24412/cl-35065-2021-1-02-55

Using SNP_TATA_Comparator [1], we studied of single-nucleotide polymorphisms in promoters of human

rheumatoid arthritis (RA)-related genes and found destabilizing selection of immunostimulatory and immuno-

suppressive genes provoking and preventing RA, respectively, , as a self-domestication syndrome. Among

known differentially expressed genes (DEGs) of pet vs wild animals, amount of DEGs in pets corresponding to

worsened RA in humans exceeds those in their wild congeners (10 vs 3), while less DEGs in pets relate relieved

RA in humans than those in Wild (1 vs 8). This is reliable according to binomial distribution, .2 and Fisher�s ex-

act tests.

This work was supported by the Russian Government Budget (grant #0259-2021-0009).

Reference

1. Ponomarenko M. P. et al. How to use SNP_TATA-Comparator to find a significant change in gene expression

caused by the regulatory SNP of this gene�s promoter via a change in affinity of the TATA-binding protein for this

promoter // BioMed. Res. Int. 2015; V. 2015. P. 359835.

Identification and classification of long noncoding RNAs

A. Pronozin, D. Afonnikov

Kurchatov Genomic Center of the Institute of Cytology and Genetics SB RAS

Email: pronozinartem95@gmail.com

DOI 10.24412/cl-35065-2021-1-02-56

Motivation and Aim: Long non-coding RNAs (lncRNAs) are typically defined as transcripts of more than

200 nucleotides length and without any protein coding potential. The functions are poorly understood, how-

ever, a number of well-known plant lncRNAs play diverse roles in X inactivation, imprinting and gene expres-

sion. Thus lncRNAs are involved in important plant development processes such as phosphate homeostasis,

flowering, photomorphogenesis and stress response in this connection, their study is relevant. Information is

obtained from transcriptomes, but bioinformatic annotation methods are not sufficiently presented, especially

for plants. This raises the challenge of developing approaches to automatic annotation and prediction of

lncRNA functions in plants.

Methods and Algorithms: In this paper a computational pipeline for the identification and annotation of

lncRNA in the plant transcriptome has been developed, steps: 1. Identification of lncRNAs � lncFinder [1]. 2.

Alignment lncRNA on referense genome � GMAP [2]. 3. lncRNAs classification � gffcompare [3]. lncRNAs struc-

tural features analysis. The pipeline is implemented using the Snakemake workflow management system lan-

guage.

Results: The pipeline was used to analyze ~ 800 Zea mays transcriptomes comprising 3148430 transcripts

in total. We identified 2741504 (87%) lncRNAs; of them 98% were aligned to the reference genome. We identi-

fied 334069 exon antisense, 4390 intron antisense, 231970 multi-exon, 81163 retained introns, 512753 inter-

genic. Antisense lncRNAs alignment (exon, intron, 338459 tr.) on structure of the target gene, showed that the

predominant amount of lncRNA is aligned on exon 1 of the target gene.

Conclusion: The proposed pipeline made it possible to identify 1164345 new lncRNAs in the maize ge-

nome, annotate them and evaluate their structural features.

Work was funded by the Kurchatov Genome Center of the Federal Research Center IC&G SB RAS, agreement with

the Ministry of Education and Science of the Russian Federation � 075-15-2019-1662.

References

1. Han S. et al. LncFinder: an integrated platform for long non-coding RNA identification utilizing sequence intrinsic

composition, structural information and physicochemical property // Briefings in bioinform. 2019. Vol. 20. No. 6.

P. 2009-2027.

2. Wu T. D., Watanabe C. K. GMAP: a genomic mapping and alignment program for mRNA and EST sequences //

Bioinform. 2005. Vol. 21. No. 9. P. 1859-1875.

3. Pertea G., Pertea M. GFF utilities: GffRead and GffCompare // F1000Research. 2020. Vol. 9.

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