Abstract
Introduction: The multi-copied genes coding for the human 18, 5.8, and 28S ribosomal RNA (rRNA) are located in five pairs of acrocentric chromosomes forming so-called rDNA. Human genome contains unmethylated, slightly methylated, and hypermethylated copies of rDNA. The major research question: What is the rDNA copy number (rDNA CN) and the content of hypermethylated rDNA as a function of age?Materials and Methods: We determined the rDNA CN in the blood leukocyte genomes of 651 subjects aged 17 to 91 years. The subjects were divided into two subgroups: “elderly” group (E-group, N = 126) – individuals over 72 years of age (the age of the population’s mean lifetime for Russia) and “non-elderly” group (NE-group, N = 525). The hypermethylated rDNA content was determined in the 40 DNA samples from the each group. The change in rDNA during replicative cell senescence was studied for the cultured skin fibroblast lines of five subjects from NE-group. Non-radioactive quantitative dot- and blot-hybridization techniques (NQH) were applied.Results: In the subjects from the E-group the mean rDNA CN was the same, but the range of variation was narrower compared to the NE-group: a range of 272 to 541 copies in E-group vs. 200 to 711 copies in NE-group. Unlike NE-group, the E-group genomes contained almost no hypermethylated rDNA copies. A case study of cultured skin fibroblasts from five subjects has shown that during the replicative senescence the genome lost hypermethylated rDNA copies only.Conclusion: In the elderly group, the mean rDNA CN is the same, but the range of variation is narrower compared with the younger subjects. During replicative senescence, the human fibroblast genome loses hypermethylated copies of rDNA. Two hypotheses were put forward: (1) individuals with either very low or very high rDNA content in their genomes do not survive till the age of the population’s mean lifetime; and/or (2) during the aging, the human genome eliminates hypermethylated copies of rDNA.
Highlights
The multi-copied genes coding for the human 18, 5.8, and 28S ribosomal RNA are located in five pairs of acrocentric chromosomes forming so-called rDNA
The diploid human genome contains ∼400 copies of a 43-kb rDNA unit tandemly arrayed in nucleolar organizer regions (NORs) on the five acrocentric chromosomes
The ribosomal RNA (rRNA)-coding region of rDNA is a problematic object for the quantification using qPCR for several reasons, which are discussed in detail in our previous articles (Korzeneva et al, 2016; Chestkov et al, 2018)
Summary
The multi-copied genes coding for the human 18, 5.8, and 28S ribosomal RNA (rRNA) are located in five pairs of acrocentric chromosomes forming so-called rDNA. Slightly methylated, and hypermethylated copies of rDNA. The human ribosome consists of two major components: ribosomal RNA (rRNA) of four types (18, 5.8, 28, and 5S) and approximately 70–80 ribosomal proteins. The rRNA and ribosomal proteins form the structure consisting of two subunits, which performs the process of translation (Khatter et al, 2015). The diploid human genome contains ∼400 copies of a 43-kb rDNA unit tandemly arrayed in nucleolar organizer regions (NORs) on the five acrocentric chromosomes. Together with the 5S rRNA (encoded by genes located on chromosome 1), these rRNAs form the nucleic acid backbone of the ribosome
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