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ORIGINAL RESEARCH article
Front. Genet.
Sec. Computational Genomics
Volume 15 - 2024 |
doi: 10.3389/fgene.2024.1472638
Number of human protein interactions correlates with structural, but not regulatory conservation of the respective genes
Provisionally accepted
Rijalda Mekic
1
Marianna A. Zolotovskaia
1,2,3*
Maxim Sorokin
1,2,3
Tharaa Mohammad
1,3*
Ivan Musatov
1
Nina Shaban
1,3
Victor Tkachev
4
Alexander Modestov
1,2
Aleksandr Simonov
1
Denis Kuzmin
1
Anton A. Buzdin
1,2,3,4,5- 1 Moscow Center for Advanced Studies, Moscow, Moscow Oblast, Russia
- 2 I.M. Sechenov First Moscow State Medical University, Moscow, Moscow Oblast, Russia
- 3 Endocrinology Research Center, Moscow, Moscow Oblast, Russia
- 4 Oncobox Corp., Moscow, Moscow Oblast, Russia
- 5 European Organisation for Research and Treatment of Cancer, Brussels, Belgium
The differential ratio of nonsynonymous to synonymous nucleotide substitutions (dN/dS) is a common measure of the rate of structural evolution in protein-coding genes. In addition, we recently suggested that the proportion of transposable elements in gene promoters that host functional genomic sites serves as a marker of the rate of regulatory evolution of genes. Such functional genomic regions may include transcription factor binding sites and modified histone binding loci.Here, we constructed a model of the human interactome based on 600,136 documented molecular interactions and investigated the overall relationship between the number of interactions of each protein and the rate of structural and regulatory evolution of the corresponding genes. By evaluating a total of 4,505 human genes and 1,936 molecular pathways we found a general correlation between structural and regulatory evolution rate metrics (Spearman 0.08-0.16 and 0.25-0.37 for gene and pathway levels, respectively, p<0.01). Further exploration revealed in the established human interactome model lack of correlation between the rate of gene regulatory evolution and the number of protein interactions on gene level, and weak negative correlation (~0.15) on pathway level. We also found a statistically significant negative correlation between the rate of gene structural evolution and the number of protein interactions (Spearman -0.11 and -0.3 for gene and pathway levels, respectively, p<0.01). This suggests stronger structural rather than regulatory conservation of genes whose protein products have multiple interaction partners.
Keywords: human gene regulation, molecular evolution, Retrospect, regulatory evolution rate, structural evolution rate, human interactome model, molecular pathways, OncoboxPD database
Received: 29 Jul 2024; Accepted: 14 Oct 2024.
Copyright: © 2024 Mekic, Zolotovskaia, Sorokin, Mohammad, Musatov, Shaban, Tkachev, Modestov, Simonov, Kuzmin and Buzdin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Marianna A. Zolotovskaia, I.M. Sechenov First Moscow State Medical University, Moscow, 119991, Moscow Oblast, Russia
Tharaa Mohammad, Endocrinology Research Center, Moscow, Moscow Oblast, Russia
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