Skip to main content

Is the number of DNA repair genes associated with evolution rate and size of genomes?

In a recent article, Voskarides et al. [1] investigated the relationship between DNA repair genes and evolution rates in vertebrates. In the last decade, there was an increase in comparative studies seeking correlation between DNA repair and longevity [2,3,4,5]. One of the reasons is also to translate this knowledge to human health and understand phenomena like aging and carcinogenesis.

The authors of the article found that the number of DNA repair genes was linearly related to the genome size and the protein number and that species that evolved through adaptive radiation have more DNA repair genes [1]. In inter-species studies, the use of linear regression and independent t test (those used by the authors) poses a serious problem: these tests assume that samples are independent, but this is not the case. In fact, the samples have different grades of dependency, which derive from their phylogenetic relationship [6]. This is why all tests should be performed using a phylogenetic correction, like phylogenetic-independent contrast [7]. Concerning the results of the article, the authors found that the number of DNA repair genes was linearly related to the genome size, but they also found that mammals have more DNA repair genes. Since mammals have larger genomes, the linear correlation is simply due to the fact that mammals are on the right of the x-axis (more repair genes) and on the top of the y-axis (larger genomes). In cases like this, phylogenetically informed analysis could reveal if within the classes and orders the linear correlation actually exists or not.

If these considerations are of general value for inter-species studies, a more specific concern as regards the “number of DNA repair genes” was found in the article. The genome and gene database of NCBI (https://0-www-ncbi-nlm-nih-gov.brum.beds.ac.uk/) is a very precious resource and, among other things, allows the user to view the list of orthologs of a specific gene. However, if a species does not appear on that list, it does not mean that it does not possess its ortholog. In the Supplementary material of the article [1], MAD2L2 is noted as absent in Rousettus aegyptiacus. Actually, it does not appear on the list of orthologs on NCBI, but it is just because it is registered as MAD2B (NCBI gene ID: 107513121), which is a synonym of MAD2L2.

Another example is MPG, which is listed as absent in Elephantulus edwardii. In fact, no gene (either listed with a synonym) can be found on NCBI. However, a BLAST search indicates that gene LOC102847768 shares 77% identity with MPG of Loxodonta africana; moreover, it is located between NPRL3 and RHBDF1, exactly as MPG in Loxodonta Africana, and its product shows the alkyladenine DNA glycosylase domain, exactly like MPG. Therefore, we can say that LOC102847768 is an ortholog of MPG, which therefore should be listed as present in Elephantulus edwardii. Besides these examples, it can be noted that many genes listed as absent in the Supplementary material of the article, in reality, are present in the NCBI lists of orthologs, e.g., in Ornithorhynchus anatinus XRCC1 (NCBI ID: 100086870), POLA1 (NCBI ID: 103168349), and BRCA1 (NCBI ID: 103167900). I have not checked all the genes in the Supplementary material, but with ease I found that all the ones listed as absent that I checked were actually present. The only exception is SLX1B, which appears to be a human novelty, arising from duplication of SLX1A.

Some studies have evidenced the different species-specific efficiency of DNA repair proteins such as 53BP1 [4] and XRCC5 [2] and the expression of DNA repair genes [3], linking them to longevity. It is, on the other hand, very improbable that some vertebrate species do not possess some genes involved in the maintenance of genome integrity, since the basic machinery of DNA repair emerged with eukaryote life and is highly conserved among animals, plants, and fungi [8]. The study on number of genes could be more useful in the field of the response to unrepaired DNA damage (apoptosis, senescence, block), where some hints indicate a greater diversity between taxa [9].

Availability of data and materials

Not applicable

References

  1. 1.

    Voskarides K, Dweep H, Chrysostomou C. Evidence that DNA repair genes, a family of tumor suppressor genes, are associated with evolution rate and size of genomes. Hum Genomics. 2019;13(1):26.

    Article  Google Scholar 

  2. 2.

    Lorenzini A, Johnson FB, Oliver A, Tresini M, Smith JS, Hdeib M, Sell C, Cristofalo VJ, Stamato TD. Significant correlation of species longevity with DNA double strand break recognition but not with telomere length. Mech Ageing Dev. 2009;130(11–12):784–92.

    CAS  Article  Google Scholar 

  3. 3.

    Fushan AA, Turanov AA, Lee SG, Kim EB, Lobanov AV, Yim SH, Buffenstein R, Lee SR, Chang KT, Rhee H, Kim JS, Yang KS, Gladyshev VN. Gene expression defines natural changes in mammalian lifespan. Aging Cell. 2015;14(3):352–65.

    CAS  Article  Google Scholar 

  4. 4.

    Croco E, Marchionni S, Bocchini M, Angeloni C, Stamato T, Stefanelli C, Hrelia S, Sell C, Lorenzini A. DNA damage detection by 53BP1: relationship to species longevity. J Gerontol A Biol Sci Med Sci. 2017;72(6):763–70.

    CAS  PubMed  Google Scholar 

  5. 5.

    Udroiu I, Sgura A. Rates of erythropoiesis in mammals and their relationship with lifespan and hematopoietic stem cells aging. Biogerontology. 2019;20(4):445–56.

    Article  Google Scholar 

  6. 6.

    Speakman JR. Correlations between physiology and lifespan--two widely ignored problems with comparative studies. Aging Cell. 2005;4(4):167–75.

    CAS  Article  Google Scholar 

  7. 7.

    Freckleton RP. Fast likelihood calculations for comparative analyses. Methods Ecol Evol. 2012;3(5):940–7.

    Article  Google Scholar 

  8. 8.

    Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell. 2010;40(2):179–204.

    CAS  Article  Google Scholar 

  9. 9.

    Sulak M, Fong L, Mika K, Chigurupati S, Yon L, Mongan NP, Emes RD, Lynch VJ. TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants. Elife. 2016;5:e11994.

Download references

Acknowledgements

Not applicable

Funding

This article received no funding.

Author information

Affiliations

Authors

Contributions

IU wrote the article. The author read and approved the final manuscript.

Corresponding author

Correspondence to Ion Udroiu.

Ethics declarations

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Competing interests

The author declares that he has no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Udroiu, I. Is the number of DNA repair genes associated with evolution rate and size of genomes?. Hum Genomics 14, 12 (2020). https://0-doi-org.brum.beds.ac.uk/10.1186/s40246-020-00259-3

Download citation