Abstract
The evolution of cancer suppression is essential for the maintenance of multicellularity. The lack of correlation between body size and cancer risk across species, known as Peto’s paradox, suggests that genetic variation in cancer resistance is sufficient to compensate for increases of cell numbers in bigger animals. To assess evolutionary dynamics of cancer-related genes, we analyzed Ka, Ks,and Ka/Ks values in 120 oncogenes and tumor suppressor genes (TSG) among seven hominoid species, including two extinct species, Neanderthal and Denisovan. Ka/Ks of tumor suppressor genes tended to be higher relative to that of oncogenes, consistent with relaxed purifying selection acting on the former. Ka/Ks values were positively correlated with TSG scores, but negatively correlated with oncogene scores, suggesting opposing selection pressures operating on the two groups of cancer-related genes. Additionally, we found 108 species-divergent substitutions that were prevalent germline genotypes in some species but in humans appeared only as somatic cancerous mutations. Better understanding the resistance to cancer may lead to new methods of cancer prevention in humans.
Similar content being viewed by others
References
Avivi A et al (2007) P53 in blind subterranean mole rats—loss-of-function versus gain-of-function activities on newly cloned Spalax target genes. Oncogene 26:2507–2512. doi:10.1038/sj.onc.1210045
Bisio A, De Sanctis V, Del Vescovo V, Denti MA, Jegga AG, Inga A, Ciribilli Y (2013) Identification of new p53 target microRNAs by bioinformatics and functional analysis. BMC Cancer 13:552. doi:10.1186/1471-2407-13-552
Blekhman R et al (2008) Natural selection on genes that underlie human disease susceptibility. Curr Biol 18:883–889
Burt A, Trivers R (2006) Genes in conflict : the biology of selfish genetic elements. Belknap Press of Harvard University Press, Cambridge
Caulin AF, Maley CC (2011) Peto’s Paradox: evolution’s prescription for cancer prevention. Trends Ecol Evol 26:175–182
Chatterjee HJ, Ho SY, Barnes I, Groves C (2009) Estimating the phylogeny and divergence times of primates using a supermatrix approach. BMC Evol Biol 9:259
Dobson JM (2013) Breed-predispositions to cancer in pedigree dogs. ISRN Vet Sci 2013:941275
Edrey YH, Hanes M, Pinto M, Mele J, Buffenstein R (2011) Successful aging and sustained good health in the naked mole rat: a long-lived mammalian model for biogerontology and biomedical research. ILAR J 52:41–53
Green RE et al (2010) A draft sequence of the Neandertal genome. Science 328:710–722
Iwasa Y, Michor F, Komarova NL, Nowak MA (2005) Population genetics of tumor suppressor genes. J Theor Biol 233:15–23
Kim EB et al (2011) Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature 479:223–227
Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci U S A 68:820–823
Li H et al (2009) The Sequence Alignment/Map format and SAMtools. Bioinformatics 25:2078–2079
Lichtenstein AV (2005) On evolutionary origin of cancer. Cancer Cell Int 5:5
Manov I et al (2013) Pronounced cancer resistance in a subterranean rodent, the blind mole-rat, Spalax: in vivo and in vitro evidence. BMC Biol 11:91
Meyer M et al (2012) A high-coverage genome sequence from an archaic Denisovan individual. Science 338:222–226
Nekrutenko A, Makova KD, Li WH (2002) The K(A)/K(S) ratio test for assessing the protein-coding potential of genomic regions: an empirical and simulation study. Genome Res 12:198–202
Nowell PC (1976) The clonal evolution of tumor cell populations. Science 194:23–28
Peto R, Roe FJ, Lee PN, Levy L, Clack J (1975) Cancer and ageing in mice and men. Br J Cancer 32:411–426
Sievers F et al (2011) Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 7:539
Thomas MA, Weston B, Joseph M, Wu W, Nekrutenko A, Tonellato PJ (2003) Evolutionary dynamics of oncogenes and tumor suppressor genes: higher intensities of purifying selection than other genes. Mol Biol Evol 20:964–968
Tian X et al (2013) High-molecular-mass hyaluronan mediates the cancer resistance of the naked mole rat. Nature 499:346–349
Vogelstein B, Kinzler KW (2002) The genetic basis of human cancer, 2nd edn. McGraw-Hill, New York
Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA Jr, Kinzler KW (2013) Cancer genome landscapes. Science 339:1546–1558
Yang Z (2007) PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24:1586–1591
Yang Z, Zhang Y, Chen L (2013) Investigation of anti-cancer mechanisms by comparative analysis of naked mole rat and rat. BMC Syst Biol 7(Suppl 2):S5
Zhang J et al (2013) Genetic heterogeneity of diffuse large B-cell lymphoma. Proc Natl Acad Sci USA 110:1398–1403
Author information
Authors and Affiliations
Corresponding author
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Kang, L., Michalak, P. The Evolution of Cancer-Related Genes in Hominoids. J Mol Evol 80, 37–41 (2015). https://doi.org/10.1007/s00239-014-9649-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00239-014-9649-5