Beyond junk DNA: Adaptive evolution of pseudogenes in vertebrates
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GRAPHICAL ABSTRACT
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PUBLIC SUMMARY
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Pseudogenes are now recognized as dynamic contributors to vertebrate adaptation and human disease.
Recurrent pseudogenization events shape immune, sensory, and metabolic adaptation in vertebrates.
In humans, pseudogenes play protective or pathogenic roles in cancer, hematopoiesis, and metabolic disorders.
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ABSTRACT
Pseudogenes, once regarded as genomic fossils or “junk DNA”, have emerged as important players in adaptive evolution of animals and regulation of human disease. In this review, we synthesize recent advances in understanding the evolutionary dynamics and functional implications of pseudogenes across vertebrates. We firstly focused on the adaptive evolution of pseudogenes in vertebrates, highlighting how pseudogenization-derived gene loss contributes to lineage-specific adaptations in diverse habitats, including immune, sensory, dietary changes, sex determination and metabolic traits. Convergent pseudogenization events have been documented across multiple species facing similar ecological challenges. We then summarized the functional roles of pseudogenes in human diseases, highlighting their dual capacity to act as either protective regulators or pathogenic drivers in cancer, hematopoiesis and metabolic disorders. These pseudogenes frequently act through non-coding networks, translation of truncated peptides, or cis-regulatory DNA elements. These advances demonstrate that pseudogenes are not passive relics but active regulators of gene expression networks. Finally, we propose that integrating long-read RNA-seq data and using CRISPR/Cas9 to test causal variants represent key future directions for dissecting pseudogene functions in evolution and disease.-
Keywords:
- pseudogenes /
- adaptive evolution /
- vertebrates /
- human disease /
- convergent evolution
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REFERENCES
[1] Mighell A., Smith N., Robinson P., et al. (2000). Vertebrate pseudogenes. FEBS Lett. 468:109−114. DOI:10.1016/s0014-5793(00)01199-6 [2] Zhang Z. D., Frankish A., Hunt T., et al. (2010). Identification and analysis of unitary pseudogenes: Historic and contemporary gene losses in humans and other primates. Genome. Biol. 11:1−17. DOI:10.1186/gb-2010-11-3-r26 [3] Balakirev E. S. and Ayala F. J. (2003). Pseudogenes: Are they "junk" or functional DNA. Annu. Rev. Genet. 37:123−151. DOI:10.1146/annurev.genet.37.040103.103949 [4] Albalat R. and Cañestro C. (2016). Evolution by gene loss. Nat. Rev. Genet. 17:379−391. DOI:10.1038/nrg.2016.39 [5] Zheng D. and Gerstein M. B. (2007). The ambiguous boundary between genes and pseudogenes: The dead rise up, or do they. Trends. Genet. 23:219−224. DOI:10.1016/j.tig.2007.03.003 [6] Pink R. C., Wicks K., Caley D. P., et al. (2011). Pseudogenes: Pseudo-functional or key regulators in health and disease. RNA 17:792−798. DOI:10.1261/rna.2658311 [7] Khan H., Smit A. and Boissinot S. (2006). Molecular evolution and tempo of amplification of human LINE-1 retrotransposons since the origin of primates. Genome. Res. 16:78−87. DOI:10.1101/gr.4001406 [8] Torrents D., Suyama M., Zdobnov E., et al. (2003). A genome-wide survey of human pseudogenes. Genome. Res. 13:2559−2567. DOI:10.1101/gr.1455503 [9] Pei B., Sisu C., Frankish A., et al. (2012). The GENCODE pseudogene resource. Genome. Biol. 13:1−26. DOI:10.1186/gb-2012-13-9-r51 [10] Poliseno L., Salmena L., Zhang J., et al. (2010). A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 465:1033−1038. DOI:10.1038/nature09144 [11] Kent W. J., Baertsch R., Hinrichs A., et al. (2003). Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes. Proc. Natl. Acad. Sci. 100:11484−11489. DOI:10.1073/pnas.1932072100 [12] Searle S. M. J., Gilbert J., Iyer V., et al. (2004). The otter annotation system. Genome. Res. 14:963−970. DOI:10.1101/gr.1864804 [13] Harrow J., Denoeud F., Frankish A., et al. (2006). GENCODE: Producing a reference annotation for ENCODE. Genome. Biol. 7:S4. DOI:10.1186/gb-2006-7-s1-s4 [14] Sharma V., Hecker N., Roscito J. G., et al. (2018). A genomics approach reveals insights into the importance of gene losses for mammalian adaptations. Nat. Commun. 9:1215. DOI:10.1038/s41467-018-03667-1 [15] Buck J. D., Wells R. S., Rhinehart H. L., et al. (2006). Aerobic microorganisms associated with free-ranging bottlenose dolphins in coastal gulf of Mexico and Atlantic ocean waters. J. Wildl. Dis. 42:536−544. DOI:10.7589/0090-3558-42.3.536 [16] Stewart J. R., Townsend F. I., Lane S. M., et al. (2014). Survey of antibiotic-resistant bacteria isolated from bottlenose dolphins Tursiops truncatus in the southeastern USA. Dis. Aquat. Org. 108:91−102. DOI:10.3354/dao02705 [17] Thornton S. M., Nolan S., Gulland F. M. J. J. o. Z., et al. (1998). Bacterial isolates from California sea lions (Zalophus californianus), harbor seals (Phoca vitulina), and northern elephant seals (Mirounga angustirostris) admitted to a rehabilitation center along the central California coast. J. Zoo Wildl. Med. 29:171−176. DOI:20095741 [18] Numberger D., Siebert U., Fulde M., et al. (2021). Streptococcal infections in marine mammals. Microorganisms 9:350. DOI:10.3390/microorganisms9020350 [19] Cha T. S., Park S. Y., Lee K. Y. L., et al. (2025). Characterization of photobacterium damselae subsp. damselae isolated from a spotted seal (Phoca largha) (Pinnipedia: Phocidae) stranded in Korea. Front. Vet. Sci. 12:1574705. DOI:10.3389/fvets.2025.1574705 [20] Sá A. L. A., Breaux B. and Burlamaqui T. C. T. (2019). The marine mammal class II major histocompatibility complex organization. Front. Immunol. 10:696. DOI:10.3389/fimmu.2019.00696 [21] Wijerathna H., Jung S. and Lee J. (2026). Enhancing Edwardsiella piscicida resistance through CRISPR/Cas9-mediated deletion of toll-like receptor 5a (tlr5a) in zebrafish. Fish Shellfish Immunol. 168:110915. DOI:10.1016/j.fsi.2025.110915 [22] Bainová H., Králová T., Bryjová A., et al. (2014). First evidence of independent pseudogenization of Toll-like receptor 5 in passerine birds. Dev. Comp. Immunol. 45:151−155. DOI:10.1016/j.dci.2014.02.010 [23] Sharma V., Hecker N., Walther F., et al. (2020). Convergent losses of TLR5 suggest altered extracellular flagellin detection in four mammalian lineages. Mol. Biol. Evol. 37:1847−1854. DOI:10.1093/molbev/msaa058 [24] Fiddaman S. R., Vinkler M., Spiro S. G., et al. (2022). Adaptation and cryptic pseudogenization in penguin toll-like receptors. Mol. Biol. Evol. 39:msab354. DOI:10.1093/molbev/msab354 [25] Wu X. Y., Chen J., Wang X. B., et al. (2022). Evolutionary impacts of pattern recognition receptor genes on carnivora complex habitat stress adaptation. Animals 12:3331. DOI:10.3390/ani12233331 [26] Krchlíková V., Hron T., Tesicky M., et al. (2023). Dynamic evolution of avian RNA virus sensors: Repeated loss of RIG-I and RIPLET. Viruses-Basel 15:3. DOI:10.3390/v15010003 [27] Sid H., von Heyl T., Schleibinger S., et al. (2025). Genetic reinstatement of RIG-I in chickens reveals insights into avian immune evolution and influenza interaction. Front. Immunol. 16:1680791. DOI:10.3389/fimmu.2025.1680791 [28] Salova M., Sipos W., Tschachler E., et al. (2022). NOD2 and reproduction-associated NOD-like receptors have been lost during the evolution of pangolins. Immunogenetics 74:261−268. DOI:10.1007/s00251-021-01230-9 [29] Birkemeier M., Swindle A., Bowman J., et al. (2024). Pervasive loss of regulated necrotic cell death genes in elephants, hyraxes, and sea cows (Paenungualta). bioRxiv DOI:10.1101/2024.04.04.588129 [30] Star B., Nederbragt A. J., Jentoft S., et al. (2011). The genome sequence of Atlantic cod reveals a unique immune system. Nature 477:207−210. DOI:10.1038/nature10342 [31] Bjornestad S. A., Solbakken M. H., Jakobsen K. S., et al. (2023). Atlantic cod (Gadus morhua) MHC I localizes to endolysosomal compartments independently of cytosolic sorting signals. Front. Cell Dev. Biol. 11:1050323. DOI:10.3389/fcell.2023.1050323 [32] Bjornestad S. A., Solbakken M. H., Krokene P., et al. (2024). The Atlantic cod MHC I compartment has the properties needed for cross-presentation in the absence of MHC II. Sci. Rep. 14:25404. DOI:10.1038/s41598-024-76225-z [33] Silver L. W., Hogg C. J. and Belov K. (2024). Plethora of new marsupial genomes informs our knowledge of marsupial MHC class II. Genome Biol. Evol. 16:evae156. DOI:10.1093/gbe/evae156 [34] Day G., Robb K., Oxley A., et al. (2024). Organisation and evolution of the major histocompatibility complex class I genes in cetaceans. iScience 27:109590. DOI:10.1016/j.isci.2024.109590 [35] Marquis A., Hubing V., Ziemann C., et al. (2024). The primate-specific presence of interferon regulatory factor-5 pseudogene 1. J. Med. Virol. 96:e29879. DOI:10.1002/jmv.29879 [36] Zhang F., Liu S. Y., Qiao Z. G., et al. (2024). Housekeeping U1 snRNA facilitates antiviral innate immunity by promoting TRIM25-mediated RIG-I activation. Cell Rep. 43:21. 113945. DOI:10.1016/j.celrep.2024.113945 [37] Naesens L., Muppala S., Acharya D., et al. (2022). GTF3A mutations predispose to herpes simplex encephalitis by disrupting biogenesis of the hostderived RIG-I ligand RNA5SP141. Sci. Immunol. 7:e4531. DOI:10.1126/sciimmunol.abq4531 [38] Müller J., Bickelmann C. and Sobral G. (2018). The evolution and fossil history of sensory perception in amniote vertebrates. Annu. Rev. Earth Planet. Sci. 46:95−519. DOI:10.1146/annurev-earth-082517-010120 [39] Simões B. F., Foley N. M., Hughes G. M., et al. (2019). As blind as a bat. Opsin phylogenetics illuminates the evolution of color vision in bats. Mol. Biol. Evol. 36:54−68. DOI:10.1093/molbev/msy192 [40] Lin J. J., Wang F. Y., Chung W. Y., et al. (2024). The genomic evolution of visual opsin genes in amphibians. Vision Res. 222:108447. DOI:10.1016/j.visres.2024.108447 [41] Gai Y., Tian R., Liu F., et al. (2023). Diversified mammalian visuasl adaptations to bright- or dim-light environments. Mol. Biol. Evol. 40:msad063. DOI:10.1093/molbev/msad063 [42] Zheng Z. Z., Hua R., Xu G. Q., et al. (2022). Gene losses may contribute to subterranean adaptations in naked mole-rat and blind mole-rat. BMC. Biol. 20. 44. DOI:10.1186/s12915-022-01243-0 [43] Wang H., Chen L., Dong C. J., et al. (2021). Genome-wide identification and characterization of olfactory receptor genes in common carp (Cyprinus carpio). Gene 777:145468. DOI:10.1016/j.gene.2021.145468 [44] Jauhal A. A., Constantine R. and Newcomb R. D. (2024). A comparative genomics approach to understanding the evolution of olfaction in cetaceans. J. Mol. Evol. 92:912−929. DOI:10.1007/s00239-024-10217-5 [45] Kang L., Chen J., Hong M., et al. (2025). Similar degenerative patterns of olfactory receptor genes in the giant panda and marine carnivores. Authorea. DOI:10.22541/au.176673629.99880144/v1 [46] Graham A. M., Saputra E., Kirilenko B., et al. (2025). Convergent reduction of olfactory genes and olfactory bulb size in mammalian species at altitude. Curr. Biol. 35:3269−3277.e4. DOI:10.1016/j.cub.2025.05.061 [47] Themudo G. E., Alves L. Q., Machado A. M., et al. (2020). Losing genes: The evolutionary remodeling of cetacea skin. Front. Mar. Sci. 7:592375. DOI:10.3389/fmars.2020.592375 [48] Springer M. S., Guerrero-Juarez C. F., Huelsmann M., et al. (2021). Genomic and anatomical comparisons of skin support independent adaptation to life in water by cetaceans and hippos. Curr. Biol. 31:2124−2139. DOI:10.1016/j.cub.2021.02.057 [49] Ehrlich F., Fischer H., Langbein L., et al. (2019). Differential evolution of the epidermal keratin cytoskeleton in terrestrial and aquatic mammals. Mol. Biol. Evol. 36:328−340. DOI:10.1093/molbev/msy214 [50] Tian R., Zhang Y. L., Kang H., et al. (2024). Sirenian genomes illuminate the evolution of fully aquatic species within the mammalian superorder afrotheria. Nat. Commun. 15:5568. DOI:10.1038/s41467-024-49769-x [51] Hocking D. P., Marx F. G., Park T., et al. (2017). A behavioural framework for the evolution of feeding in predatory aquatic mammals. Proc. R. Soc. B 284:20162750. DOI:10.1098/rspb.2016.2750 [52] Ocampo M., Pincheira-Donoso D. and Rios R. S. (2024). Patterns of morphological diversification are influenced by dietary evolution in a highly species-rich lizard radiation. Front. Ecol. Evol. 12:1361799. DOI:10.3389/fevo.2024.1361799 [53] Shaheen J., Mudd A. B., Diekwisch T. G. H., et al. (2021). Pseudogenized amelogenin reveals early tooth loss in true toads (Anura: Bufonidae). Integr. Comp. Biol. 61:1933−1945. DOI:10.1093/icb/icab039 [54] Lappin A. K., Monroy J. A., Pilarski J. Q., et al. (2006). Storage and recovery of elastic potential energy powers ballistic prey capture in toads. J. Exp. Biol. 209:2535−2553. DOI:10.1242/jeb.02276 [55] Emerling C. A., Gibb G. C., Tilak M. K., et al. (2023). Genomic data suggest parallel dental vestigialization within the xenarthran radiation. Peer Community J. 3:e75. DOI:10.24072/pcjournal.303 [56] Springer M. S., Emerling C. A., Gatesy J., et al. (2019). Odontogenic ameloblast-associated (ODAM) is inactivated in toothless/enamelless placental mammals and toothed whales. BMC. Evol. Biol. 19:31. DOI:10.1186/s12862-019-1359-6 [57] Mu Y., Huang X., Liu R., et al. (2021). ACPT gene is inactivated in mammalian lineages that lack enamel or teeth. Peerj 9:e10219. DOI:10.7717/peerj.10219 [58] Zhong H., Huang J., Shang S., et al. (2021). Evolutionary insights into umami, sweet, and bitter taste receptors in amphibians. Ecol. Evol. 11:18011−18025. DOI:10.1002/ece3.8398 [59] Nishihara H., Toda Y., Kuramoto T., et al. (2024). A vertebrate-wide catalogue of T1R receptors reveals diversity in taste perception. Nat. Ecol. Evol. 8:111−120. DOI:10.1038/s41559-023-02258-8 [60] Wolsan M. and Sato J. J. (2022). Role of feeding specialization in taste receptor loss: Insights from sweet and umami receptor evolution in Carnivora. Chem. Senses 47:bjac033. DOI:10.1093/chemse/bjac033 [61] Lu Q., Jiao H., Wang Y., et al. (2021). Molecular evolution and deorphanization of bitter taste receptors in a vampire bat. Integr. Zool. 16:659−669. DOI:10.1111/1749-4877.12509 [62] Shan L., Wu Q., Wang L., et al. (2018). Lineage-specific evolution of bitter taste receptor genes in the giant and red pandas implies dietary adaptation. Integr. Zool. 13:152−159. DOI:10.1111/1749-4877.12291 [63] Chen Y. H. and Zhao H. B. (2019). Evolution of digestive enzymes and dietary diversification in birds. Peerj 7:e6840. DOI:10.7717/peerj.6840 [64] Zhang F. H., Xu N., Yu Y. S., et al. (2019). Expression profile of the digestive enzymes of Manis javanica reveals its adaptation to diet specialization. Acs Omega 4:19925−19933. DOI:10.1021/acsomega.9b02845 [65] Li G. T., Wei H. Y., Bi J. J., et al. (2020). Insights into dietary switch in cetaceans: Evidence from molecular evolution of proteinases and lipases. J. Mol. Evol. 88:521−535. DOI:10.1007/s00239-020-09952-2 [66] Lang D., Zhao J., Liu S., et al. (2025). Adaptive evolution of pancreatic ribonuclease gene (RNase1) in Cetartiodactyla. Integr. Zool. 20:1265−1277. DOI:10.1111/1749-4877.12895 [67] Hecker N., Sharma V. and Hiller M. (2019). Convergent gene losses illuminate metabolic and physiological changes in herbivores and carnivores. Proc. Natl. Acad. Sci. 116:3036−3041. DOI:10.1073/pnas.1818504116 [68] Jiao H., Zhang L., Xie H.-W., et al. (2019). Trehalase gene as a molecular signature of dietary diversification in mammals. Mol. Biol. Evol. 36:2171−2183. DOI:10.1093/molbev/msz127 [69] Smith C. A., McClive P. J., Western P. S., et al. (1999). Conservation of a sex-determining gene. Nature 402:601−602. DOI:10.1038/45130 [70] Suda M., Uno Y., Fujii J., et al. (2011). Isolation and characterization of the CYP17A1 gene and its processed pseudogene in Rana rugosa. Comp. Biochem. Physiol. B Biochem. Mol. Biol. 160:54−61. DOI:10.1016/j.cbpb.2011.05.008 [71] Bewick A. J., Anderson D. W. and Evans B. J. (2011). Evolution of the closely related, sex‐related genes DM‐W and DMRT1 in African clawed frogs (Xenopus). Evolution 65:698−712. DOI:10.1111/j.1558-5646.2010.01163.x [72] Kuhl H., Euclide P. T. and Klopp C. (2024). Multi-genome comparisons reveal gain-and-loss evolution of anti-Mullerian hormone receptor type 2 as a candidate master sex-determining gene in Percidae. BMC. Biol. 22:141. DOI:10.1186/s12915-024-01935-9 [73] Bachtrog D. (2013). Y-chromosome evolution: Emerging insights into processes of Y-chromosome degeneration. Nat. Rev. Genet. 14:113−124. DOI:10.1038/nrg3366 [74] Wilson Sayres M. A. and Makova K. D. (2013). Gene survival and death on the human Y chromosome. Mol. Biol. Evol. 30:781−787. DOI:10.1093/molbev/mss267 [75] Murtagh V. J., O'Meally D., Sankovic N., et al. (2012). Evolutionary history of novel genes on the tammar wallaby Y chromosome: Implications for sex chromosome evolution. Genome. Res. 22:498−507. DOI:10.1101/gr.120790.111 [76] Zhou Y., Zhan X. and Jin J. (2023). Eighty million years of rapid evolution of the primate Y chromosome. Ecol. Evol. 7:1114−1130. DOI:10.1038/s41559-022-01974-x [77] Carlisle J. A., Bickell A. L. and Hart M. W. (2025). Sexual selection and pseudogenization in primate fertilization. Evolution 79:1670−1680. DOI:10.1093/evolut/qpaf072 [78] Osipova E., Barsacchi R., Brown T., et al. (2023). Loss of a gluconeogenic muscle enzyme contributed to adaptive metabolic traits in hummingbirds. Science 379:185−190. DOI:10.1126/science.abn7050 [79] Zhou M., Wu T., Chen Y., et al. (2022). Functional attenuation of UCP1 as the potential mechanism for a thickened blubber layer in cetaceans. Mol. Biol. Evol. 39:msac230. DOI:10.1093/molbev/msac230 [80] Tian R., Zhang T., Dong H., et al. (2025). Cetacean loss of the master adipose tissue regulator β3-adrenergic receptor may underlie their thick blubber and an Oligocene radiation and dispersal. Nat. Commun. 16:9235. DOI:10.1038/s41467-025-64288-z [81] Rudolf A. M., Wu Q., Li L., et al. (2022). A single nucleotide mutation in the dual-oxidase 2 (DUOX2) gene causes some of the panda's unique metabolic phenotypes. Natl. Sci. Rev. 9:nwab125. DOI:10.1093/nsr/nwab125 [82] Nie Y., Speakman J. R., Wu Q., et al. (2015). Exceptionally low daily energy expenditure in the bamboo-eating giant panda. Science 349:171−174. DOI:10.1126/science.aab2413 [83] Lou W., Ding B. and Fu P. (2020). Pseudogene-derived lncRNAs and their miRNA sponging mechanism in human cancer. Front. Cell Dev. Biol. 8:85. DOI:10.3389/fcell.2020.00085 [84] Nourbakhsh S. T., Mohamadhashem F., Soltani Fard E., et al. (2026). Emerging roles of pseudogene-derived lncRNAs in cancer stem cells: Non-coding clues and therapeutic targets in cancer medicine. Genes Dis. 13:101793. DOI:10.1016/j.gendis.2025.101793 [85] Nie L., Li C., Zhao T., et al. (2020). LncRNA double homeobox A pseudogene 8 (DUXAP8) facilitates the progression of neuroblastoma and activates Wnt/β-catenin pathway via microRNA-29/nucleolar protein 4 like (NOL4L) axis. Brain Res. 1746:146947. DOI:10.1016/j.brainres.2020.146947 [86] Rodriguez J. M., Maquedano M., Cerdán-Vélez D., et al. (2025). An audit of the PeptideAtlas database uncovers evidence for repurposed pseudogenes and co-opted retroviral ORFs. BMC Genomics 26:1087. DOI:10.1186/s12864-025-12238-w [87] Sun M., Ma Y. and Yu J. (2025). From genomic fossils to functional elements: The evolving story of pseudogenes. Adv. Genet. 6:e00040. DOI:10.1002/ggn2.202500040 [88] Salmena L., Poliseno L., Tay Y., et al. (2011). A ceRNA hypothesis: The Rosetta stone of a hidden RNA language. Cell 146:353−358. DOI:10.1016/j.cell.2011.07.014 [89] Ghafouri-Fard S., Khoshbakht T., Hussen B. M., et al. (2022). A review on the role of PTENP1 in human disorders with an especial focus on tumor suppressor role of this lncRNA. Cancer Cell Int. 22:207. DOI:10.1186/s12935-022-02625-8 [90] Chen X. J., Zhu H., Wu X. L., et al. (2016). Downregulated pseudogene CTNNAP1 promote tumor growth in human cancer by downregulating its cognate gene CTNNA1 expression. Oncotarget 7:55518−55528. DOI:10.18632/oncotarget.10833 [91] Ni Q., An M., Luo S., et al. (2023). Pseudogene TDGF1P3 regulates the proliferation and metastasis of colorectal cancer cells via the miR-338-3p–PKM2 axis. Biochem. Biophys. Res. Commun. 638:7−13. DOI:10.1016/j.bbrc.2022.11.054 [92] Di Sanzo M., Quaresima B., Biamonte F., et al. (2020). FTH1 pseudogenes in cancer and cell metabolism. Cells 9:2554. DOI:10.3390/cells9122554 [93] Hwang S. L., Chang J. H., Cheng C. Y., et al. (2005). The expression of rac1 pseudogene in human tissues and in human brain tumors. Eur. Surg. Res. 37:100−104. DOI:10.1159/000084540 [94] Ma Y. N., Liu S. Q., Gao J., et al. (2021). Genome-wide analysis of pseudogenes reveals HBBP1's human-specific essentiality in erythropoiesis and implication in β-thalassemia. Dev. Cell 56:478−493. DOI:10.1016/j.devcel.2020.12.019 [95] Zhou L. Y., Zhai L. L., Yin J. Y., et al. (2016). Pseudogene BMI1P1 expression as a novel predictor for acute myeloid leukemia development and prognosis. Oncotarget 7:47376−47386. DOI:10.18632/oncotarget.10156 [96] Li L. and Zhao W. D. (2021). The mutual regulatory loop between TPTEP1 and miR-1303 in leukemogenesis of acute myeloid leukemia. Cancer Cell Int. 21:260. DOI:10.1186/s12935-021-01966-0 [97] Ziyad S., Riordan J. D., Cavanaugh A. M., et al. (2018). A forward genetic screen targeting the endothelium reveals a regulatory role for the lipid kinase Pi4ka in myelo-and erythropoiesis. Cell Rep. 22:1211−1224. DOI:10.1016/j.celrep.2018.01.017 [98] Pappalardo X. G., Risiglione P., Zinghirino F., et al. (2023). Human VDAC pseudogenes: An emerging role for VDAC1P8 pseudogene in acute myeloid leukemia. Biol. Res. 56:33. DOI:10.1186/s40659-023-00446-1 [99] Sidransky E. and Lopez G. (2012). The link between the GBA gene and parkinsonism. Lancet Neurol. 11:986−998. DOI:10.1016/S1474-4422(12)70190-4 [100] Straniero L., Rimoldi V. and Samarani M. (2017). The GBAP1 pseudogene acts as a ceRNA for the glucocerebrosidase gene GBA by sponging miR-22-3p. Sci. Rep. 7:12702. DOI:10.1038/s41598-017-12973-5 [101] Chen J., Li C., Wang Y., et al. (2025). Identify new pseudogene RPL7P1-oriented network as a drug target against infections pre-existing diabetes. Integr. Biol. 17:zyaf015. DOI:10.1093/intbio/zyaf015 [102] Edgar A. J. (2002). The human L-threonine 3-dehydrogenase gene is an expressed pseudogene. BMC. Genet. 3:18. DOI:10.1186/1471-2156-3-18 [103] McEntee G., Minguzzi S., O'Brien K., et al. (2011). The former annotated human pseudogene dihydrofolate reductase-like 1 (DHFRL1) is expressed and functional. Proc. Natl. Acad. Sci. 108:15157−15162. DOI:10.1073/pnas.1103605108 -
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Jin Z., Meng X., Zhao L., et al. (2026). Beyond junk DNA: Adaptive evolution of pseudogenes in vertebrates. The Innovation Life 4:100240. https://doi.org/10.59717/j.xinn-life.2026.100240
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Jin Z., Meng X., Zhao L., et al. (2026). Beyond junk DNA: Adaptive evolution of pseudogenes in vertebrates. The Innovation Life 4:100240. https://doi.org/10.59717/j.xinn-life.2026.100240
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Figure 1.
Major classes of eukaryotic pseudogenes
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Figure 2.
Pseudogenization of genes involved in innate and adaptive immunity in vertebrates
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Figure 3.
Pseudogenization of sensory-related genes in habitat-adapted vertebrates
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Figure 4.
Pseudogenization of dietary-related genes in vertebrates
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Figure 5.
Pseudogenes involved in human diseases
