The Chromosomal-Boundary Paradox of Processed Pseudogene Annotation in the T2T Era

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Far from being inert genomic debris, these retrocopies have contributed to gene diversification and regulatory innovation across mammalian lineages. With the completion of telomere-to-telomere (T2T) human genome assemblies, many such loci have been found within duplication-dense pericentromeric and subtelomeric regions. These dynamic chromosomal boundaries frequently undergo recombination and segmental duplication, raising the possibility that an initial retrocopy insertion can act as a structural seed for subsequent DNA-level propagation. Notably, the insertion and duplication of the SEPTIN14 3′ terminal exon produced the composite CICP-SEPTIN14P co-mobilized gene unit underlying the CICP pseudogene family. Under current morphology-based annotation systems, such loci are automatically classified as processed pseudogenes, highlighting the limitation of appearance-driven annotation that overlooks mechanistic origin and duplication history. Results: The CICP-SEPTIN14P pair constitutes a co-mobilized gene unit that exemplifies how a processed pseudogene and its parental gene can propagate together as a single duplication block across chromosomal boundaries. Comparative inspection of the GRCh38.p14 and T2T-CHM13v2.0 assemblies identified 28 CICP loci in the human genome, most of which share sequence similarity with SEPTIN14. Approximately two-thirds of these loci are positioned within or adjacent to telomeric, subtelomeric, centromeric, or pericentromeric regions. The putative ancestral copy, CICP12, appears to be a processed pseudogene embedded within the final intron of SEPTIN14, forming the original co-mobilized gene unit that was subsequently propagated to multiple chromosomes through segmental duplication. Sequence alignments revealed extended tracts of > 90% identity among pericentromeric and subtelomeric members, supporting a model in which an integrated CICP-SEPTIN14P block was duplicated as a whole rather than generated by independent retrotransposition events. Expression profiling based on GTEx data showed that CICP16 and SEPTIN14P4 display strikingly similar expression patterns across multiple human tissues, suggesting that this co-mobilized duplication unit retained coordinated regulatory behavior after relocation. Comparable tendencies across other CICP-SEPTIN14P pairs reinforce the view that segmentally duplicated, co-mobilized gene units can preserve joint transcriptional control under shared chromatin environments, demonstrating that boundary-linked duplication can maintain regulatory synchrony even after integration into distinct chromosomal contexts. Conclusions: The CICP-SEPTIN14P co-mobilized gene unit illustrates how a processed pseudogene can transform into a duplication-driven expansion module once integrated near a chromosomal boundary. To avoid systematic misclassification of such loci as independent retrocopies, I propose the Chromosomal Boundary-Associated Processed Pseudogene framework. This model flags any parental gene, pseudogene, or related fragment located within telomeric, subtelomeric, centromeric, or pericentromeric regions and automatically extends the flag to all members of the same gene family for manual review. In addition, I recommend formally recognizing segmentally duplicated processed pseudogenes, defined as processed pseudogenes that later underwent DNA-level block duplication. Together, these measures establish an evolution-aware annotation strategy that integrates chromosomal context into pseudogene classification, offering a framework for improving genome annotation and interpretation in the post-T2T era. Processed pseudogene Segmental duplication Telomere-to-telomere assembly Chromosomal boundary Retrotransposition Centromeric duplication SEPTIN14 Annotation error Figures Figure 1 Figure 2 Figure 3 Background Processed pseudogenes-retrotransposed, intronless copies of expressed mRNAs-represent a major legacy of LINE-1 activity in mammalian genomes[ 1 , 2 ]. Their annotation traditionally relies on three structural hallmarks: loss of introns, a poly(A) tail, and the presence of short target-site duplications (TSDs) [ 3 ]. However, these features alone cannot distinguish RNA-mediated retrocopies from DNA-level duplications that replicate existing pseudogenes. The distinction became blurred with the advent of long-read sequencing and optical mapping [ 4 – 6 ]. The telomere-to-telomere (T2T) human genome assembly resolved nearly all centromeric and subtelomeric gaps, revealing vast duplication blocks, alpha-satellite arrays, and lineage-specific repeats extending into euchromatic arms [ 7 , 8 ]. These boundary regions-long thought to be inert heterochromatin-are now recognized as dynamic hubs of recombination and segmental duplication [ 9 , 10 ]. Segmental duplication studies have shown that intronless genes can also arise by DNA-mediated replication events[ 11 , 12 ]. In humans and other primates, such events cluster near pericentromeric and subtelomeric zones [ 13 , 14 ], suggesting that chromosomal boundaries serve as engines of genome plasticity. Yet annotation pipelines have not integrated this spatial context, treating every intronless locus as a potential retrocopy. The CICP-SEPTIN14P co-mobilization exemplifies this challenge. CICP12 , a processed pseudogene derived from SEPTIN14 -a testis-enriched GTPase involved in cytoskeletal organization [ 15 ]-is uniquely embedded within an intron of its own parental gene (7p11.2). This configuration produced a composite duplication block ( SEPTIN14 + CICP12 ) that subsequently propagated across the genome, giving rise to the CICP1-CICP28 family. Many copies localize to chromosomal boundaries, indicating that once a processed pseudogene integrates into such a dynamic region, it can act as a duplication seed. Results Phylogenetic and structural conservation of the CICP gene family Maximum-likelihood (ML) phylogenetic inference using IQ-TREE 2 and ModelFinder Plus (1,000 ultrafast bootstraps) grouped the pericentromeric and subtelomeric CICP loci into a single duplication-derived clade, distinct from canonical LINE-1-mediated retrocopies [ 17 ]. The analysis, based on a 13,151 bp alignment of 28 CICP loci, yielded a well-resolved topology with strong statistical support across all major branches (ultrafast bootstrap correlation = 0.996). The best-fitting substitution model selected by ModelFinder Plus was GTR + F + R3, consistent under both AIC and BIC, indicating moderate among-site rate heterogeneity under a free-rate model. Base-composition χ² testing revealed significant heterogeneity among sequences, with 14 of 28 loci (including CICP10, CICP12, CICP13, CICP14, CICP15, CICP22, CICP24, and CICP28) failing the compositional homogeneity test (p < 0.05). These loci are predominantly situated in pericentromeric or subtelomeric domains, suggesting regional GC-content shifts linked to chromatin context or boundary-associated duplication activity. To assess local sequence conservation, each CICP region (gene ± 10 kb) was divided into 100 bp bins, and pairwise identity was calculated as the proportion of non-gapped identical positions between reference and query sequences. In Fig. 2a and Fig. 2b, the resulting matrices revealed extended tracts (> 4 kb) with ≥ 90% identity extending beyond the pseudogene boundaries, consistent with DNA-level block duplications rather than independent retrocopy insertions [ 11 , 16 ]. In Fig. 2c, when ordered according to ML-based phylogenetic distance, pericentromeric and subtelomeric members clustered tightly, exhibiting continuous high-identity regions corresponding to duplication blocks evident in the phylogenetic tree. Notably, CICP12-the ancestral locus of the family-lies within the final intron of SEPTIN14 in the same transcriptional orientation. The locus contains a canonical poly(A) tail and flanking target site duplications (TSDs), confirming its origin as a processed retrocopy. Its integration within an active pericentromeric duplication domain suggests that this embedded retrocopy acted as a duplication seed, initiating subsequent rounds of DNA-level propagation of the surrounding genomic block [12,18,19]. Collectively, the ML phylogeny, base-composition profiles, and 100 bp-binned identity analyses delineate three major positional clusters -subtelomeric, pericentromeric, and interstitial- and together support a model in which the CICP-SEPTIN14P family expanded not through recurrent retroposition but through chromosomal boundary-linked segmental duplications seeded by the ancestral CICP12 retrocopy, preserving both sequence architecture and syntenic relationships across loci. Violin and dot plots showing tissue-specific TPM distributions of CICP16 (top) and its co-mobilized paralogue SEPTIN14P4 (bottom) across 54 human tissues from the GTEx v10 dataset. Tissues are ordered by the median expression of CICP16 to maintain a consistent axis alignment.Both genes exhibit low-level yet coherent expression patterns in testis and brain, supporting retention of shared regulatory features within the duplicated CICP-SEPTIN14P block. Conserved co-expression of the CICP-SEPTIN14P module Analysis of GTEx v8 transcript abundance profiles revealed that CICP16 and SEPTIN14P4 exhibit highly concordant expression across human tissues, particularly in the testis and brain, where both show low-level. The nearly identical tissue-specific expression patterns and magnitude of expression suggest that these two loci are not independently transcribed pseudogenes but rather components of a co-mobilized duplication block that has preserved the ancestral regulatory architecture of the SEPTIN14-CICP12 composite unit. Such coordinated expression supports the interpretation that duplication of this genomic module propagated both the sequence and its associated cis-regulatory environment. The persistence of matched transcriptional echoes between CICP16 and SEPTIN14P4 implies that boundary-linked duplication can transmit chromatin context and residual promoter activity intact, producing duplicated pseudogene pairs that retain synchronized regulatory signatures despite their noncoding status. Collectively, these results reinforce the model that chromosomal boundary-linked segmental duplication not only preserved sequence identity but also maintained vestiges of regulatory coupling, thereby extending the concept of pseudogene inheritance from mere structural replication to include transcriptional coherence across duplicated loci. Table 1. Chromosomal distribution and co-mobilization patterns of the CICP-SEPTIN14P gene family This table summarizes the cytoband positions, chromosomal location types, and co-mobilized SEPTIN14 paralogues of all 28 CICP pseudogenes identified in the human genome. Each locus is classified as interstitial, subtelomeric, pericentromeric, or centromeric according to cytogenetic band position, revealing that 17 of 28 loci (61%) are positioned near chromosomal boundaries. Co-mobilized SEPTIN14P loci denote paralogues duplicated together with their corresponding CICP copies, reflecting coordinated propagation through boundary-linked segmental duplication. This table provides an overview of the CICP-SEPTIN14P genomic relationship; full genomic coordinates, Ensembl gene IDs, and cross-database annotation sources are presented in Supplementary Data 2. Systematic misannotation of the CICP gene family despite full manual curation The CICP gene family—comprising 28 pseudogenes—is comprehensively represented and consistently annotated across Ensembl, NCBI Gene, RefSeq, and pseudogene.org. All CICP loci, including CICP5, CICP25, and CICP26, are explicitly recorded as manually curated by the HAVANA project, and both the CICP and SEPTIN14P families have been formally approved by the HUGO Gene Nomenclature Committee (HGNC). In other words, this family represents one of the highest levels of genomic annotation consensus and expert manual validation currently achievable across independent international databases. Despite this extensive curation, the CICP family displays a critical inconsistency. While most loci are correctly annotated as processed pseudogenes, three members—CICP5 (1q36.33), CICP25 (16q24.3), and CICP26 (1q42.13)—remain classified as unprocessed pseudogenes in all major reference databases. Comparative genomic analysis demonstrates that these three loci are not genuine unprocessed pseudogenes but rather retrocopy-derived block duplications that retain partial intronic fragments introduced during secondary DNA-level propagation. Co-mobilization with SEPTIN14P paralogues occurs in 22 of 28 loci (78%), indicating that the majority of CICP copies were replicated as part of a composite SEPTIN14-CICP12 unit rather than as independent retrocopy insertions. Each of the three misclassified loci maintains syntenic linkage to a specific SEPTIN14P paralogue: CICP5 (1q36.33) co-mobilized with SEPTIN14P15, forming an intrachromosomal duplication pair. CICP25 (16q24.3) located within a pericentromeric duplication block, likely representing a truncated derivative of a CICP-SEPTIN14 module. CICP26 (1q42.13) co-duplicated with SEPTIN14P16, forming a segmental duplication cassette. These relationships clearly show that CICP5, CICP25, and CICP26 originated through DNA-level segmental duplication of pre-existing processed retrocopies, not by direct duplication of intron-containing parental genes. They are therefore processed in origin but duplicated in structure—misclassified as “unprocessed” solely because of partial exon-intron relics introduced during duplication. Critical annotation paradox The persistence of this misclassification is particularly notable because it occurs despite manual curation under the HAVANA project—a framework specifically established for expert-reviewed annotation within Ensembl and RefSeq. This inconsistency exposes a structural limitation of current pseudogene-classification logic, which relies almost exclusively on the presence of retained introns as the defining criterion for “unprocessed” pseudogenes. Such a morphology-based rule cannot discriminate between a truly unprocessed pseudogene duplicated directly from a coding gene, and a retrocopy-derived pseudogene that subsequently underwent DNA-level segmental duplication. As a result, loci that share identical evolutionary origins and duplication mechanisms are inconsistently labeled—some as processed, others as unprocessed—based purely on residual intronic morphology. This highlights a form-dependent bias in genome annotation, where mechanistically equivalent events are divided into separate categories because of superficial post-duplication sequence features. The CICP loci therefore exemplify a systemic blind spot in current pseudogene ontology: static structural descriptors are prioritized over mechanistic context, obscuring the recursive, multi-phase duplication processes that shaped the CICP-SEPTIN14P complex and distorting our broader understanding of pseudogene evolution within duplication-prone chromosomal boundaries. Evolutionary interpretation and framework revision Collectively, these findings reveal that present-day annotation systems frequently conflate structural form with evolutionary origin, misclassifying retrocopy-derived duplications as unprocessed pseudogenes merely because they retain partial exon-intron remnants. Accordingly, all CICP pseudogenes—except CICP12, the founding retrocopy—should be re-annotated as segmentally duplicated processed pseudogenes, denoting elements that originated via retroposition but subsequently propagated through DNA-level duplication. To address this broader issue, we propose a Chromosomal Boundary-Associated Annotation Framework for future genome curation. Under this model, any pseudogene or parental gene located within or adjacent to telomeric, subtelomeric, centromeric, or pericentromeric regions will be automatically flagged as “Chromosomal Boundary-Associated”, regardless of its current annotation or origin. This flag does not alter formal classification but serves as a universal caution marker for manual review across all members of the corresponding gene family. Such chromosomal-boundary-aware annotation highlights loci most likely shaped by boundary-linked segmental duplication, reducing overestimation of independent retrocopy formation. Incorporating this boundary-aware context—together with formal recognition of segmentally duplicated processed pseudogenes—provides a practical and evolution-aware framework for capturing the recursive, multi-layered mechanisms that drive pseudogene evolution in boundary-rich genomic environments. Discussion The phenomenon of co-mobilized CICP-SEPTIN14P illustrates a mechanistic bridge between retrotransposition and segmental duplication. The CICP12 retrocopy first inserted into its parental gene, generating a composite block that later propagated across chromosomal boundaries via duplication. Once embedded in dynamic pericentromeric or subtelomeric contexts, the processed pseudogene became a structural seed for multi-chromosomal expansion-a process aligning with recent models of chromosomal boundary-driven genome evolution [ 9 , 16 ]. This dual mechanism reveals a limitation of current pseudogene annotation: structure-based classifiers overlook chromosomal context, conflating duplication products with independent retrocopies[ 3 ]. Proposed framework: Chromosomal Boundary-Associated Processed Pseudogene model integrating segmentally duplicated processed pseudogenes To resolve the limitations observed in current pseudogene classification, I propose the Chromosomal Boundary-Associated Processed Pseudogene framework, a context-aware annotation approach that directly incorporates chromosomal position and structural mechanism into pseudogene categorization. Within this framework, any parental gene, pseudogene, or homologous fragment located within 5 Mb of a centromeric or telomeric boundary should be automatically flagged as chromosomal boundary-associated for manual review. This flagging does not alter the initial computational classification but serves to identify loci likely generated by boundary-linked duplication events, which are common in both pericentromeric and subtelomeric heterochromatic regions. Integrating this positional information into automated pipelines would prevent the systematic overestimation of retrocopy-derived pseudogenes in genomic environments characterized by high duplication and recombination rates. Incorporating the chromosomal boundary dimension allows annotation systems to distinguish genuine retroposition events from DNA-level block duplications that mimic processed pseudogene structure. In addition, I propose a new subclass of pseudogenes-the segmentally duplicated processed pseudogene-to designate processed pseudogenes that have subsequently undergone DNA-level segmental duplication. This subclass captures the evolutionary nature of loci such as CICP5 (1q36.33) , CICP25 (16q24.3) , and CICP26 (1q42.13) , which originated via retrotransposition but later propagated through chromosomal duplication. By explicitly recognizing these as segmentally duplicated processed pseudogenes, annotation systems can maintain consistency between molecular origin and structural evolution, rather than conflating such cases with true unprocessed pseudogenes. Together, the Chromosomal Boundary-Associated Processed Pseudogene framework and the segmentally duplicated processed pseudogene subclass provide an integrated evolutionary and structural model for pseudogene annotation. This approach preserves the efficiency of automated computational pipelines while ensuring that loci influenced by centromeric and telomeric boundary dynamics are accurately classified. Applied to the CICP and SEPTIN14P families, this model resolves the paradox of processed-origin pseudogenes that were later duplicated as DNA blocks but remain mislabeled as unprocessed pseudogenes across major databases. Conceptual summary Framework element Definition Function 1. Chromosomal Boundary-Associated Processed Pseudogene Any pseudogene or parental gene located within telomeric, subtelomeric, centromeric, or pericentromeric regions; the flag extends to all members of the same gene family. Marks boundary-linked families for manual curation 2. Segmentally Duplicated Processed pseudogene Processed pseudogene that later underwent DNA-level segmental duplication Mechanistic subclassification Conceptual impact The Chromosomal Boundary-Associated Processed Pseudogene model redefines pseudogene annotation in evolutionary terms. It explicitly acknowledges that centromeric and telomeric boundaries act as duplication accelerators, shaping recurrent cycles of retrogene propagation and block-level re-duplication. By uniting positional context with mechanistic subclassification, this model offers a biologically coherent alternative to current annotation schemes that depend solely on exon-intron structure. Its adoption by major curation frameworks such as Ensembl, RefSeq, and HAVANA would prevent conceptual mislabeling of boundary-linked pseudogenes, ensuring that cases like all CICP-SEPTIN14P are correctly recognized as retrocopy-derived pseudogenes duplicated through chromosomal boundary-linked mechanisms. Conclusion The structural delineation of telomeric, subtelomeric, centromeric, and precentromeric regions provides an essential framework for understanding the organization and stability of the human genome. Telomeres, composed of tandem TTAGGG repeats stabilized by the shelterin complex, protect chromosome termini from degradation and end-to-end fusion during replication. Immediately adjacent subtelomeric domains, typically spanning 100–500 kb, exhibit high sequence variability and are enriched for low-copy repeats, pseudogenes, and lineage-specific gene families such as olfactory receptors and zinc finger clusters. These regions act as recombination-prone boundaries that facilitate chromosomal diversification and contribute to species-specific genomic architecture. In contrast, the centromere and its flanking precentromeric region form the mechanical and epigenetic core required for accurate chromosome segregation. The precentromere, extending several hundred kilobases to a few megabases outward from α-satellite arrays, represents a heterochromatic transition zone that mediates centromeric chromatin propagation and kinetochore stability. Together, these terminal domains constitute complementary structural elements that preserve chromosomal integrity while enabling localized evolutionary flexibility. Among countless instances of such structural dynamics, this study simplified this complexity by presenting the co-mobilization of the CICP and SEPTIN14P loci as a representative example. This case exemplifies how gene families and their associated pseudogene counterparts can undergo coordinated relocation events within subtelomeric, precentromeric and even interstitial landscapes, reflecting the evolutionary fluidity of these boundary domains. The completion of the telomere-to-telomere (T2T-CHM13) assembly has, for the first time, resolved these complex genomic regions in their entirety. This continuity demonstrates that subtelomeric and precentromeric regions are not passive structural margins but dynamic genomic interfaces that balance chromosomal stability, recombination, and long-term evolutionary innovation in eukaryotic genomes. To ensure accurate manual annotation and prevent errors, genes located within these structurally complex boundaries should be automatically flagged for caution. While structured curation remains indispensable, relying solely on structural frameworks limits our understanding of the evolutionary logic underlying these regions. Integrating block-level duplication analysis and family-based classification will provide a more comprehensive perspective on the replication and diversification of chromosomal domains. Such integrative and hierarchical curation will be crucial for advancing the systematic interpretation of genomic data and for deepening our understanding of biological processes in the post-T2T era. Methods Genome assemblies and annotation Coordinates for CICP1-CICP28 were retrieved from GENCODE Release 49 (GRCh38.p14 primary assembly). All CICP loci are officially approved by the HUGO Gene Nomenclature Committee (HGNC) and are consistently curated across Ensembl, NCBI Gene, RefSeq, and Pseudogene.org databases. Each locus is explicitly documented as manually annotated by the HAVANA project, confirming expert curation of processed pseudogene status and genomic boundaries. The annotation was cross-validated using the UCSC “CHM13 alignment” track (T2T-CHM13v2.0), which confirmed the continuity of CICP loci within pericentromeric and subtelomeric duplication blocks that were previously unresolved in GRCh38. For sequence analysis, ± 10 kb flanking regions around each CICP locus were extracted using pyfaidx v0.7.2. All coordinates were handled in 1-based closed intervals; terminal gaps were padded with “N” characters to ensure consistent sequence lengths. All sequences were oriented according to the strand of CICP12, the inferred ancestral insertion and duplication seed. Phylogenetic analysis of CICP loci For each CICP locus, a 20 kb genomic segment encompassing the gene (± 10 kb flanking regions) was extracted from the GRCh38.p14 assembly. Multiple sequence alignments were performed using MAFFT v7.505 with the --auto option (FFT-NS-2 mode) and eight computational threads. Alignments were automatically trimmed to remove poorly aligned positions using trimAl v1.4.rev15 with the -automated1 parameter. The resulting trimmed alignments were used to infer maximum-likelihood (ML) phylogenies in IQ-TREE 2, applying ModelFinder Plus (MFP) to determine the best-fitting nucleotide substitution model. The GTR + F + R3 model was selected based on the Bayesian Information Criterion (BIC), and branch support was assessed with 1,000 ultrafast bootstrap replicates (-B 1000). Phylogenetic distances obtained from the IQ-TREE output were subsequently used for downstream comparative visualization. Expression analysis Raw transcriptomic data were obtained from the GTEx v10 release [ 17 ]through the GTEx portal ( https://gtexportal.org ). The gene-level TPM matrix file and the sample annotation file were downloaded directly from the public repository. Data extraction and visualization were performed using Python 3.11. A custom script processed the GTEx GCT file in chunked mode to efficiently retrieve the target genes (CICP16, SEPTIN14P4). The resulting TPM values were merged with sample metadata (fields SMTS and SMTSD) using pandas v2.2. TPM values were transformed as log₁₀(TPM + 1) prior to plotting.Tissue order was determined by the median expression of CICP16 and applied consistently across all genes to preserve axis alignment. Violin and dot plots were generated using seaborn v0.13 and Matplotlib v3.9 to visualize tissue-specific expression profiles. Expression concordance between CICP16 and its co-mobilized partners (SEPTIN14P4) was qualitatively evaluated based on similarity of tissue-specific distribution patterns. Declarations Ethics approval and consent to participate Not applicable. This study did not involve human participants, animal subjects, or any other ethical approval requirements. Consent for publication Not applicable. Availability of data and materials All genomic and transcriptomic resources used in this study are publicly available from the following repositories: Ensembl Genome Browser: https://www.ensembl.org UCSC Genome Browser: https://genome.ucsc.edu National Center for Biotechnology Information (NCBI) Gene: https://www.ncbi.nlm.nih.gov/gene HUGO Gene Nomenclature Committee (HGNC): https://www.genenames.org Genotype-Tissue Expression (GTEx) Project, v10: https://gtexportal.org/home/ Python Software Foundation (Python 3.10): https://www.python.org All datasets were accessed under open-use terms and contain no controlled-access or human-identifiable information and are included in this published article and its supplementary materials. Additional datasets or scripts are available from the corresponding author upon reasonable request. Competing interests The author declares no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Authors' contributions The author solely conceived, designed, analyzed, and wrote the manuscript. Acknowledgements The author acknowledges the HAVANA project for building the manual annotation foundation that continues to inspire deeper examination and refinement of genomic annotation logic in the post-T2T era. References Esnault C, Maestre J, Heidmann T. Mechanism LINE-1 retrotransposition mammalian cells. Nat Genet. 2000;24:363–7. Kaessmann H, Vinckenbosch N, Long M. RNA-based gene duplication: mechanistic and evolutionary insights. Nat Rev Genet. 2009;10:19–31. Zhang Y. Comprehensive catalog processed pseudogenes human mouse. Genome Biol Evol. 2020;12:2730–45. Vollger MR. Segmental duplications centromere architecture T2T-CHM13 genome. Cell. 2023;186:635–50. Chaisson MJP, Huddleston J, Dennis MY, Sudmant PH, Malig M, Hormozdiari F, et al. Resolving the complexity of the human genome using single-molecule sequencing. Nature. 2015;517:608–11. Jain M, Koren S, Miga KH, Quick J, Rand AC, Sasani TA, et al. Nanopore sequencing and assembly of a human genome with ultra-long reads. Nat Biotechnol. 2018;36:338–45. Bailey JA, Yavor AM, Massa HF, Trask BJ, Eichler EE. Segmental duplications: organization and impact within the current human genome project assembly. Genome Res. 2001;11:1005–17. Smits P. Satellite DNA dynamics chromosomal boundaries. Nat Genet. 2023;55:112–23. Marques-Bonet T, Eichler EE. burst segmental duplications human lineage. Nat Rev Genet. 2009;10:845–54. Eichler EE. Genetic variation, comparative genomics, future human evolution. Nat Rev Genet. 2019;20:431–44. Bailey JA, Gu Z, Clark RA, Reinert K, Samonte RV, Schwartz S, et al. Recent segmental duplications in the human genome. Science. 2002;297:1003–7. Feng X. Higher rates processed pseudogene acquisition recently active genomes. Mol Biol Evol. 2021;38:2958–68. Linardopoulou EV, Williams EM, Fan Y, Friedman C, Young JM, Trask BJ. Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication. Nature. 2005;437:94–100. Bailey JA, Eichler EE. Primate segmental duplications: crucibles of evolution, diversity and disease. Nat Rev Genet. 2006;7:552–64. Hall PA. Septins biology cell division. Nat Rev Mol Cell Biol. 2005;6:451–61. Feng Z, Cheng Y. Evolutionary plasticity human subtelomeric duplication blocks. Nat Commun. 2022;13. GTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45:580–5. Additional Declarations No competing interests reported. Supplementary Files SupplementaryData1.pdf SupplementaryData2.xlsx Cite Share Download PDF Status: Published Journal Publication published 17 Feb, 2026 Read the published version in Mobile DNA → Version 1 posted Editorial decision: Revision requested 15 Dec, 2025 Reviews received at journal 13 Dec, 2025 Reviews received at journal 09 Dec, 2025 Reviewers agreed at journal 25 Nov, 2025 Reviewers agreed at journal 11 Nov, 2025 Reviewers invited by journal 09 Nov, 2025 Editor assigned by journal 03 Nov, 2025 Submission checks completed at journal 31 Oct, 2025 First submitted to journal 30 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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07:39:41","extension":"xml","order_by":15,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":60498,"visible":true,"origin":"","legend":"","description":"","filename":"26d9da59061c458583c010714a303c431structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7991770/v1/4add05d329fce7e6dd3a43dd.xml"},{"id":95657185,"identity":"8a0b383b-4561-484d-8daf-a5077e2b8013","added_by":"auto","created_at":"2025-11-11 16:20:15","extension":"html","order_by":16,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":67415,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7991770/v1/23d079eb135c3f9e62f35902.html"},{"id":95609548,"identity":"9a2f2194-7020-4ff9-858f-d1bc24869a57","added_by":"auto","created_at":"2025-11-11 07:39:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":246712,"visible":true,"origin":"","legend":"\u003cp\u003eThe paradox of processed pseudogene annotation across the pre-T2T, T2T, and post-T2T eras.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e(a)\u003c/strong\u003e Conceptual overview showing how completion of telomere-to-telomere (T2T) assemblies redefined pseudogene annotation logic. Before the T2T era, processed pseudogenes were identified solely by structural hallmarks—target site duplications (TSDs), exon-exon junctions, and poly(A) tails—assuming independent retrocopy origin. Completion of gap-free assemblies revealed that many of these loci lie within pericentromeric and subtelomeric regions enriched for recombination and duplication, exposing the limitations of structure-only annotation. In the post-T2T era, accurate interpretation requires integrating chromosomal context, where chromosoaml boundary-associated duplication can secondarily propagate pre-existing retrocopies. \u003cstrong\u003e(b)\u003c/strong\u003e Schematic model depicting LINE-1-mediated retrotransposition of the \u003cem\u003eCIC\u003c/em\u003etranscript and subsequent integration into the final intron of \u003cem\u003eSEPTIN14\u003c/em\u003e in the same transcriptional orientation, generating \u003cem\u003eCICP12\u003c/em\u003e as a processed pseudogene. The \u003cem\u003eCICP12\u003c/em\u003e locus (≈ 831 bp) lies approximately 1.9 kb downstream of the \u003cem\u003eSEPTIN14\u003c/em\u003e terminal exon (≈ 2.5 kb in length). This composite configuration represents the structural seed of a duplication block that was later mobilized to other chromosomes during boundary-linked segmental duplication.\u003c/p\u003e","description":"","filename":"image1.png","url":"https://assets-eu.researchsquare.com/files/rs-7991770/v1/fe7df24b9c3480922ca1bffa.png"},{"id":95609551,"identity":"240d7931-6878-4396-bda4-7e839c524ddb","added_by":"auto","created_at":"2025-11-11 07:39:39","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":162894,"visible":true,"origin":"","legend":"\u003cp\u003eStructural and syntenic conservation of the CICP-SEPTIN14P gene family.\u003c/p\u003e\n\u003ch4\u003eThis figure illustrates the comparative sequence conservation and phylogenetic relationships among CICP pseudogenes and their co-mobilized SEPTIN14P paralogues. For each CICP locus, a 20 kb genomic region (gene ±10 kb) was aligned using MAFFT v7.505, and alignments were trimmed with trimAl v1.4.rev15. Maximum-likelihood (ML) phylogenetic trees were reconstructed in IQ-TREE 2 using ModelFinder Plus (MFP) and 1,000 ultrafast bootstrap replicates. Panels (a) and (b) show representative pairwise identity heatmaps for CICP12 and CICP27, visualized as 100 bp-binned similarity matrices. Panel (c) presents an ML tree derived from the same dataset, with branch annotations indicating chromosomal location types - ST (subtelomeric), IS (interstitial), and PC (pericentromeric). These analyses provide a comparative framework for assessing structural and positional conservation within the CICP-SEPTIN14P duplication system. Full alignments, phylogenetic trees, and pairwise identity data for all 28 loci are provided in Supplementary Data 1\u003c/h4\u003e","description":"","filename":"image2.png","url":"https://assets-eu.researchsquare.com/files/rs-7991770/v1/66299993407a9432701048a8.png"},{"id":95609554,"identity":"ce73315a-abd4-46f0-884c-eb6746b456c2","added_by":"auto","created_at":"2025-11-11 07:39:39","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":359388,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFigure 4.\u003c/strong\u003e Tissue-wide expression concordance between co-mobilized CICP and SEPTIN14P loci\u003c/p\u003e\n\u003cp\u003eViolin and dot plots showing tissue-specific TPM distributions of CICP16 (top) and its co-mobilized paralogue SEPTIN14P4 (bottom) across 54 human tissues from the GTEx v10 dataset. Tissues are ordered by the median expression of CICP16 to maintain a consistent axis alignment.Both genes exhibit low-level yet coherent expression patterns in testis and brain, supporting retention of shared regulatory features within the duplicated CICP-SEPTIN14P block.\u003c/p\u003e","description":"","filename":"image3.png","url":"https://assets-eu.researchsquare.com/files/rs-7991770/v1/64132f91daab164ee80b9f2d.png"},{"id":103251493,"identity":"55dd9800-f029-46a7-86b9-50ef5faae181","added_by":"auto","created_at":"2026-02-23 16:09:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1928469,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7991770/v1/34840513-6cd1-4553-a511-2406a5c34881.pdf"},{"id":95609549,"identity":"5d398ab3-e98f-4901-964c-73f613ccc95e","added_by":"auto","created_at":"2025-11-11 07:39:38","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":701553,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryData1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7991770/v1/c5f8e993572839c4856918a6.pdf"},{"id":95609561,"identity":"df11de51-16af-4201-81cf-3db5f691c80f","added_by":"auto","created_at":"2025-11-11 07:39:40","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":11500,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryData2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7991770/v1/2e91745ef19793b7534f6bf2.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Chromosomal-Boundary Paradox of Processed Pseudogene Annotation in the T2T Era","fulltext":[{"header":"Background","content":"\u003cp\u003eProcessed pseudogenes-retrotransposed, intronless copies of expressed mRNAs-represent a major legacy of LINE-1 activity in mammalian genomes[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Their annotation traditionally relies on three structural hallmarks: loss of introns, a poly(A) tail, and the presence of short target-site duplications (TSDs) [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, these features alone cannot distinguish RNA-mediated retrocopies from DNA-level duplications that replicate existing pseudogenes.\u003c/p\u003e\u003cp\u003eThe distinction became blurred with the advent of long-read sequencing and optical mapping [\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. The telomere-to-telomere (T2T) human genome assembly resolved nearly all centromeric and subtelomeric gaps, revealing vast duplication blocks, alpha-satellite arrays, and lineage-specific repeats extending into euchromatic arms [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These boundary regions-long thought to be inert heterochromatin-are now recognized as dynamic hubs of recombination and segmental duplication [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSegmental duplication studies have shown that intronless genes can also arise by DNA-mediated replication events[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In humans and other primates, such events cluster near pericentromeric and subtelomeric zones [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], suggesting that chromosomal boundaries serve as engines of genome plasticity. Yet annotation pipelines have not integrated this spatial context, treating every intronless locus as a potential retrocopy.\u003c/p\u003e\u003cp\u003eThe CICP-SEPTIN14P co-mobilization exemplifies this challenge. \u003cem\u003eCICP12\u003c/em\u003e, a processed pseudogene derived from \u003cem\u003eSEPTIN14\u003c/em\u003e-a testis-enriched GTPase involved in cytoskeletal organization [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]-is uniquely embedded within an intron of its own parental gene (7p11.2). This configuration produced a composite duplication block (\u003cem\u003eSEPTIN14\u0026thinsp;+\u0026thinsp;CICP12\u003c/em\u003e) that subsequently propagated across the genome, giving rise to the \u003cem\u003eCICP1-CICP28\u003c/em\u003e family. Many copies localize to chromosomal boundaries, indicating that once a processed pseudogene integrates into such a dynamic region, it can act as a duplication seed.\u003c/p\u003e"},{"header":"Results","content":"\u003ch3\u003ePhylogenetic and structural conservation of the CICP gene family\u003c/h3\u003e\n\u003cp\u003eMaximum-likelihood (ML) phylogenetic inference using IQ-TREE 2 and ModelFinder Plus (1,000 ultrafast bootstraps) grouped the pericentromeric and subtelomeric CICP loci into a single duplication-derived clade, distinct from canonical LINE-1-mediated retrocopies [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. The analysis, based on a 13,151 bp alignment of 28 CICP loci, yielded a well-resolved topology with strong statistical support across all major branches (ultrafast bootstrap correlation\u0026thinsp;=\u0026thinsp;0.996). The best-fitting substitution model selected by ModelFinder Plus was GTR\u0026thinsp;+\u0026thinsp;F\u0026thinsp;+\u0026thinsp;R3, consistent under both AIC and BIC, indicating moderate among-site rate heterogeneity under a free-rate model. Base-composition χ\u0026sup2; testing revealed significant heterogeneity among sequences, with 14 of 28 loci (including CICP10, CICP12, CICP13, CICP14, CICP15, CICP22, CICP24, and CICP28) failing the compositional homogeneity test (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). These loci are predominantly situated in pericentromeric or subtelomeric domains, suggesting regional GC-content shifts linked to chromatin context or boundary-associated duplication activity. To assess local sequence conservation, each CICP region (gene\u0026thinsp;\u0026plusmn;\u0026thinsp;10 kb) was divided into 100 bp bins, and pairwise identity was calculated as the proportion of non-gapped identical positions between reference and query sequences. In Fig.\u0026nbsp;2a and Fig.\u0026nbsp;2b, the resulting matrices revealed extended tracts (\u0026gt;\u0026thinsp;4 kb) with \u0026ge;\u0026thinsp;90% identity extending beyond the pseudogene boundaries, consistent with DNA-level block duplications rather than independent retrocopy insertions [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In Fig.\u0026nbsp;2c, when ordered according to ML-based phylogenetic distance, pericentromeric and subtelomeric members clustered tightly, exhibiting continuous high-identity regions corresponding to duplication blocks evident in the phylogenetic tree. Notably, CICP12-the ancestral locus of the family-lies within the final intron of SEPTIN14 in the same transcriptional orientation. The locus contains a canonical poly(A) tail and flanking target site duplications (TSDs), confirming its origin as a processed retrocopy. Its integration within an active pericentromeric duplication domain suggests that this embedded retrocopy acted as a duplication seed, initiating subsequent rounds of DNA-level propagation of the surrounding genomic block [12,18,19]. Collectively, the ML phylogeny, base-composition profiles, and 100 bp-binned identity analyses delineate three major positional clusters -subtelomeric, pericentromeric, and interstitial- and together support a model in which the CICP-SEPTIN14P family expanded not through recurrent retroposition but through chromosomal boundary-linked segmental duplications seeded by the ancestral CICP12 retrocopy, preserving both sequence architecture and syntenic relationships across loci.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eViolin and dot plots showing tissue-specific TPM distributions of CICP16 (top) and its co-mobilized paralogue SEPTIN14P4 (bottom) across 54 human tissues from the GTEx v10 dataset. Tissues are ordered by the median expression of CICP16 to maintain a consistent axis alignment.Both genes exhibit low-level yet coherent expression patterns in testis and brain, supporting retention of shared regulatory features within the duplicated CICP-SEPTIN14P block.\u003c/p\u003e\n\u003ch3\u003eConserved co-expression of the CICP-SEPTIN14P module\u003c/h3\u003e\n\u003cp\u003eAnalysis of GTEx v8 transcript abundance profiles revealed that \u003cem\u003eCICP16\u003c/em\u003e and \u003cem\u003eSEPTIN14P4\u003c/em\u003e exhibit highly concordant expression across human tissues, particularly in the testis and brain, where both show low-level. The nearly identical tissue-specific expression patterns and magnitude of expression suggest that these two loci are not independently transcribed pseudogenes but rather components of a co-mobilized duplication block that has preserved the ancestral regulatory architecture of the \u003cem\u003eSEPTIN14-CICP12\u003c/em\u003e composite unit. Such coordinated expression supports the interpretation that duplication of this genomic module propagated both the sequence and its associated cis-regulatory environment. The persistence of matched transcriptional echoes between \u003cem\u003eCICP16\u003c/em\u003e and \u003cem\u003eSEPTIN14P4\u003c/em\u003e implies that boundary-linked duplication can transmit chromatin context and residual promoter activity intact, producing duplicated pseudogene pairs that retain synchronized regulatory signatures despite their noncoding status.\u003c/p\u003e\u003cp\u003eCollectively, these results reinforce the model that chromosomal boundary-linked segmental duplication not only preserved sequence identity but also maintained vestiges of regulatory coupling, thereby extending the concept of pseudogene inheritance from mere structural replication to include transcriptional coherence across duplicated loci.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e Chromosomal distribution and co-mobilization patterns of the CICP-SEPTIN14P gene family\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cimg width=\"363\" height=\"432\" 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\" alt=\"image\"\u003e\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThis table summarizes the cytoband positions, chromosomal location types, and co-mobilized SEPTIN14 paralogues of all 28 CICP pseudogenes identified in the human genome. Each locus is classified as interstitial, subtelomeric, pericentromeric, or centromeric according to cytogenetic band position, revealing that 17 of 28 loci (61%) are positioned near chromosomal boundaries. Co-mobilized SEPTIN14P loci denote paralogues duplicated together with their corresponding CICP copies, reflecting coordinated propagation through boundary-linked segmental duplication. This table provides an overview of the CICP-SEPTIN14P genomic relationship; full genomic coordinates, Ensembl gene IDs, and cross-database annotation sources are presented in Supplementary Data 2.\u003c/p\u003e\n\u003ch3\u003eSystematic misannotation of the CICP gene family despite full manual curation\u003c/h3\u003e\n\u003cp\u003eThe CICP gene family\u0026mdash;comprising 28 pseudogenes\u0026mdash;is comprehensively represented and consistently annotated across Ensembl, NCBI Gene, RefSeq, and pseudogene.org. All CICP loci, including CICP5, CICP25, and CICP26, are explicitly recorded as manually curated by the HAVANA project, and both the CICP and SEPTIN14P families have been formally approved by the HUGO Gene Nomenclature Committee (HGNC). In other words, this family represents one of the highest levels of genomic annotation consensus and expert manual validation currently achievable across independent international databases.\u003c/p\u003e\u003cp\u003eDespite this extensive curation, the CICP family displays a critical inconsistency. While most loci are correctly annotated as processed pseudogenes, three members\u0026mdash;CICP5 (1q36.33), CICP25 (16q24.3), and CICP26 (1q42.13)\u0026mdash;remain classified as unprocessed pseudogenes in all major reference databases. Comparative genomic analysis demonstrates that these three loci are not genuine unprocessed pseudogenes but rather retrocopy-derived block duplications that retain partial intronic fragments introduced during secondary DNA-level propagation. Co-mobilization with SEPTIN14P paralogues occurs in 22 of 28 loci (78%), indicating that the majority of CICP copies were replicated as part of a composite SEPTIN14-CICP12 unit rather than as independent retrocopy insertions. Each of the three misclassified loci maintains syntenic linkage to a specific SEPTIN14P paralogue:\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eCICP5 (1q36.33) co-mobilized with SEPTIN14P15, forming an intrachromosomal duplication pair.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCICP25 (16q24.3) located within a pericentromeric duplication block, likely representing a truncated derivative of a CICP-SEPTIN14 module.\u003c/p\u003e\u003c/li\u003e\u003cli\u003e\u003cp\u003eCICP26 (1q42.13) co-duplicated with SEPTIN14P16, forming a segmental duplication cassette.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e\u003cp\u003eThese relationships clearly show that CICP5, CICP25, and CICP26 originated through DNA-level segmental duplication of pre-existing processed retrocopies, not by direct duplication of intron-containing parental genes. They are therefore processed in origin but duplicated in structure\u0026mdash;misclassified as \u0026ldquo;unprocessed\u0026rdquo; solely because of partial exon-intron relics introduced during duplication.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eCritical annotation paradox\u003c/h2\u003e\u003cp\u003eThe persistence of this misclassification is particularly notable because it occurs despite manual curation under the HAVANA project\u0026mdash;a framework specifically established for expert-reviewed annotation within Ensembl and RefSeq.\u0026nbsp;This inconsistency exposes a structural limitation of current pseudogene-classification logic, which relies almost exclusively on the presence of retained introns as the defining criterion for \u0026ldquo;unprocessed\u0026rdquo; pseudogenes. Such a morphology-based rule cannot discriminate between\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ea truly unprocessed pseudogene duplicated directly from a coding gene, and\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003ea retrocopy-derived pseudogene that subsequently underwent DNA-level segmental duplication.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eAs a result, loci that share identical evolutionary origins and duplication mechanisms are inconsistently labeled\u0026mdash;some as processed, others as unprocessed\u0026mdash;based purely on residual intronic morphology. This highlights a form-dependent bias in genome annotation, where mechanistically equivalent events are divided into separate categories because of superficial post-duplication sequence features. The CICP loci therefore exemplify a systemic blind spot in current pseudogene ontology: static structural descriptors are prioritized over mechanistic context, obscuring the recursive, multi-phase duplication processes that shaped the CICP-SEPTIN14P complex and distorting our broader understanding of pseudogene evolution within duplication-prone chromosomal boundaries.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eEvolutionary interpretation and framework revision\u003c/h3\u003e\n\u003cp\u003eCollectively, these findings reveal that present-day annotation systems frequently conflate structural form with evolutionary origin, misclassifying retrocopy-derived duplications as unprocessed pseudogenes merely because they retain partial exon-intron remnants. Accordingly, all CICP pseudogenes\u0026mdash;except CICP12, the founding retrocopy\u0026mdash;should be re-annotated as segmentally duplicated processed pseudogenes, denoting elements that originated via retroposition but subsequently propagated through DNA-level duplication.\u003c/p\u003e\u003cp\u003eTo address this broader issue, we propose a Chromosomal Boundary-Associated Annotation Framework for future genome curation. Under this model, any pseudogene or parental gene located within or adjacent to telomeric, subtelomeric, centromeric, or pericentromeric regions will be automatically flagged as \u0026ldquo;Chromosomal Boundary-Associated\u0026rdquo;, regardless of its current annotation or origin. This flag does not alter formal classification but serves as a universal caution marker for manual review across all members of the corresponding gene family.\u003c/p\u003e\u003cp\u003eSuch chromosomal-boundary-aware annotation highlights loci most likely shaped by boundary-linked segmental duplication, reducing overestimation of independent retrocopy formation. Incorporating this boundary-aware context\u0026mdash;together with formal recognition of segmentally duplicated processed pseudogenes\u0026mdash;provides a practical and evolution-aware framework for capturing the recursive, multi-layered mechanisms that drive pseudogene evolution in boundary-rich genomic environments.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe phenomenon of co-mobilized \u003cem\u003eCICP-SEPTIN14P\u003c/em\u003e illustrates a mechanistic bridge between retrotransposition and segmental duplication. The \u003cem\u003eCICP12\u003c/em\u003e retrocopy first inserted into its parental gene, generating a composite block that later propagated across chromosomal boundaries via duplication. Once embedded in dynamic pericentromeric or subtelomeric contexts, the processed pseudogene became a structural seed for multi-chromosomal expansion-a process aligning with recent models of chromosomal boundary-driven genome evolution [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This dual mechanism reveals a limitation of current pseudogene annotation: structure-based classifiers overlook chromosomal context, conflating duplication products with independent retrocopies[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eProposed framework: Chromosomal Boundary-Associated Processed Pseudogene model integrating segmentally duplicated processed pseudogenes\u003c/h2\u003e\u003cp\u003eTo resolve the limitations observed in current pseudogene classification, I propose the Chromosomal Boundary-Associated Processed Pseudogene framework, a context-aware annotation approach that directly incorporates chromosomal position and structural mechanism into pseudogene categorization. Within this framework, any parental gene, pseudogene, or homologous fragment located within 5 Mb of a centromeric or telomeric boundary should be automatically flagged as \u003cem\u003echromosomal boundary-associated\u003c/em\u003e for manual review. This flagging does not alter the initial computational classification but serves to identify loci likely generated by boundary-linked duplication events, which are common in both pericentromeric and subtelomeric heterochromatic regions. Integrating this positional information into automated pipelines would prevent the systematic overestimation of retrocopy-derived pseudogenes in genomic environments characterized by high duplication and recombination rates. Incorporating the chromosomal boundary dimension allows annotation systems to distinguish genuine retroposition events from DNA-level block duplications that mimic processed pseudogene structure.\u003c/p\u003e\u003cp\u003eIn addition, I propose a new subclass of pseudogenes-the segmentally duplicated processed pseudogene-to designate processed pseudogenes that have subsequently undergone DNA-level segmental duplication. This subclass captures the evolutionary nature of loci such as \u003cem\u003eCICP5 (1q36.33)\u003c/em\u003e, \u003cem\u003eCICP25 (16q24.3)\u003c/em\u003e, and \u003cem\u003eCICP26 (1q42.13)\u003c/em\u003e, which originated via retrotransposition but later propagated through chromosomal duplication. By explicitly recognizing these as segmentally duplicated processed pseudogenes, annotation systems can maintain consistency between molecular origin and structural evolution, rather than conflating such cases with true unprocessed pseudogenes.\u003c/p\u003e\u003cp\u003eTogether, the Chromosomal Boundary-Associated Processed Pseudogene framework and the segmentally duplicated processed pseudogene subclass provide an integrated evolutionary and structural model for pseudogene annotation. This approach preserves the efficiency of automated computational pipelines while ensuring that loci influenced by centromeric and telomeric boundary dynamics are accurately classified. Applied to the \u003cem\u003eCICP\u003c/em\u003e and \u003cem\u003eSEPTIN14P\u003c/em\u003e families, this model resolves the paradox of processed-origin pseudogenes that were later duplicated as DNA blocks but remain mislabeled as unprocessed pseudogenes across major databases.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eConceptual summary\u003c/h2\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFramework element\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDefinition\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFunction\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1. Chromosomal Boundary-Associated Processed Pseudogene\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAny pseudogene or parental gene located within telomeric, subtelomeric, centromeric, or pericentromeric regions; the flag extends to all members of the same gene family.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMarks boundary-linked families for manual curation\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2. Segmentally Duplicated Processed pseudogene\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eProcessed pseudogene that later underwent DNA-level segmental duplication\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMechanistic subclassification\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eConceptual impact\u003c/h2\u003e\u003cp\u003eThe Chromosomal Boundary-Associated Processed Pseudogene model redefines pseudogene annotation in evolutionary terms. It explicitly acknowledges that centromeric and telomeric boundaries act as duplication accelerators, shaping recurrent cycles of retrogene propagation and block-level re-duplication. By uniting positional context with mechanistic subclassification, this model offers a biologically coherent alternative to current annotation schemes that depend solely on exon-intron structure. Its adoption by major curation frameworks such as Ensembl, RefSeq, and HAVANA would prevent conceptual mislabeling of boundary-linked pseudogenes, ensuring that cases like all CICP-SEPTIN14P are correctly recognized as retrocopy-derived pseudogenes duplicated through chromosomal boundary-linked mechanisms.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe structural delineation of telomeric, subtelomeric, centromeric, and precentromeric regions provides an essential framework for understanding the organization and stability of the human genome. Telomeres, composed of tandem TTAGGG repeats stabilized by the shelterin complex, protect chromosome termini from degradation and end-to-end fusion during replication. Immediately adjacent subtelomeric domains, typically spanning 100\u0026ndash;500 kb, exhibit high sequence variability and are enriched for low-copy repeats, pseudogenes, and lineage-specific gene families such as olfactory receptors and zinc finger clusters. These regions act as recombination-prone boundaries that facilitate chromosomal diversification and contribute to species-specific genomic architecture. In contrast, the centromere and its flanking precentromeric region form the mechanical and epigenetic core required for accurate chromosome segregation. The precentromere, extending several hundred kilobases to a few megabases outward from α-satellite arrays, represents a heterochromatic transition zone that mediates centromeric chromatin propagation and kinetochore stability. Together, these terminal domains constitute complementary structural elements that preserve chromosomal integrity while enabling localized evolutionary flexibility.\u003c/p\u003e\u003cp\u003eAmong countless instances of such structural dynamics, this study simplified this complexity by presenting the co-mobilization of the CICP and SEPTIN14P loci as a representative example. This case exemplifies how gene families and their associated pseudogene counterparts can undergo coordinated relocation events within subtelomeric, precentromeric and even interstitial landscapes, reflecting the evolutionary fluidity of these boundary domains.\u003c/p\u003e\u003cp\u003eThe completion of the telomere-to-telomere (T2T-CHM13) assembly has, for the first time, resolved these complex genomic regions in their entirety. This continuity demonstrates that subtelomeric and precentromeric regions are not passive structural margins but dynamic genomic interfaces that balance chromosomal stability, recombination, and long-term evolutionary innovation in eukaryotic genomes. To ensure accurate manual annotation and prevent errors, genes located within these structurally complex boundaries should be automatically flagged for caution. While structured curation remains indispensable, relying solely on structural frameworks limits our understanding of the evolutionary logic underlying these regions. Integrating block-level duplication analysis and family-based classification will provide a more comprehensive perspective on the replication and diversification of chromosomal domains. Such integrative and hierarchical curation will be crucial for advancing the systematic interpretation of genomic data and for deepening our understanding of biological processes in the post-T2T era.\u003c/p\u003e\u003c/div\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003cdiv id=\"Sec16\" class=\"Section3\"\u003e\u003ch2\u003eGenome assemblies and annotation\u003c/h2\u003e\u003cp\u003eCoordinates for CICP1-CICP28 were retrieved from GENCODE Release 49 (GRCh38.p14 primary assembly). All CICP loci are officially approved by the HUGO Gene Nomenclature Committee (HGNC) and are consistently curated across Ensembl, NCBI Gene, RefSeq, and Pseudogene.org databases. Each locus is explicitly documented as manually annotated by the HAVANA project, confirming expert curation of processed pseudogene status and genomic boundaries. The annotation was cross-validated using the UCSC \u0026ldquo;CHM13 alignment\u0026rdquo; track (T2T-CHM13v2.0), which confirmed the continuity of CICP loci within pericentromeric and subtelomeric duplication blocks that were previously unresolved in GRCh38. For sequence analysis, \u0026plusmn;\u0026thinsp;10 kb flanking regions around each CICP locus were extracted using pyfaidx v0.7.2. All coordinates were handled in 1-based closed intervals; terminal gaps were padded with \u0026ldquo;N\u0026rdquo; characters to ensure consistent sequence lengths. All sequences were oriented according to the strand of CICP12, the inferred ancestral insertion and duplication seed.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003ePhylogenetic analysis of CICP loci\u003c/h2\u003e\u003cp\u003eFor each \u003cem\u003eCICP\u003c/em\u003e locus, a 20 kb genomic segment encompassing the gene (\u0026plusmn;\u0026thinsp;10 kb flanking regions) was extracted from the GRCh38.p14 assembly. Multiple sequence alignments were performed using MAFFT v7.505 with the --auto option (FFT-NS-2 mode) and eight computational threads. Alignments were automatically trimmed to remove poorly aligned positions using trimAl v1.4.rev15 with the -automated1 parameter. The resulting trimmed alignments were used to infer maximum-likelihood (ML) phylogenies in IQ-TREE 2, applying ModelFinder Plus (MFP) to determine the best-fitting nucleotide substitution model. The GTR\u0026thinsp;+\u0026thinsp;F\u0026thinsp;+\u0026thinsp;R3 model was selected based on the Bayesian Information Criterion (BIC), and branch support was assessed with 1,000 ultrafast bootstrap replicates (-B 1000). Phylogenetic distances obtained from the IQ-TREE output were subsequently used for downstream comparative visualization.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eExpression analysis\u003c/h2\u003e\u003cp\u003eRaw transcriptomic data were obtained from the GTEx v10 release [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]through the GTEx portal (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://gtexportal.org\u003c/span\u003e\u003cspan address=\"https://gtexportal.org\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). The gene-level TPM matrix file and the sample annotation file were downloaded directly from the public repository. Data extraction and visualization were performed using Python 3.11. A custom script processed the GTEx GCT file in chunked mode to efficiently retrieve the target genes (CICP16, SEPTIN14P4). The resulting TPM values were merged with sample metadata (fields SMTS and SMTSD) using pandas v2.2. TPM values were transformed as log₁₀(TPM\u0026thinsp;+\u0026thinsp;1) prior to plotting.Tissue order was determined by the median expression of CICP16 and applied consistently across all genes to preserve axis alignment. Violin and dot plots were generated using seaborn v0.13 and Matplotlib v3.9 to visualize tissue-specific expression profiles. Expression concordance between CICP16 and its co-mobilized partners (SEPTIN14P4) was qualitatively evaluated based on similarity of tissue-specific distribution patterns.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This study did not involve human participants, animal subjects, or any other ethical approval requirements.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll genomic and transcriptomic resources used in this study are publicly available from the following repositories:\u003c/p\u003e\n\u003cp\u003eEnsembl Genome Browser: https://www.ensembl.org\u003c/p\u003e\n\u003cp\u003eUCSC Genome Browser: https://genome.ucsc.edu\u003c/p\u003e\n\u003cp\u003eNational Center for Biotechnology Information (NCBI) Gene: https://www.ncbi.nlm.nih.gov/gene\u003c/p\u003e\n\u003cp\u003eHUGO Gene Nomenclature Committee (HGNC): https://www.genenames.org\u003c/p\u003e\n\u003cp\u003eGenotype-Tissue Expression (GTEx) Project, v10: https://gtexportal.org/home/\u003c/p\u003e\n\u003cp\u003ePython Software Foundation (Python 3.10): https://www.python.org\u003c/p\u003e\n\u003cp\u003eAll datasets were accessed under open-use terms and contain no controlled-access or human-identifiable information and are included in this published article and its supplementary materials. Additional datasets or scripts are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author declares no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author solely conceived, designed, analyzed, and wrote the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author acknowledges the HAVANA project for building the manual annotation foundation that continues to inspire deeper examination and refinement of genomic annotation logic in the post-T2T era.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEsnault C, Maestre J, Heidmann T. Mechanism LINE-1 retrotransposition mammalian cells. Nat Genet. 2000;24:363\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKaessmann H, Vinckenbosch N, Long M. RNA-based gene duplication: mechanistic and evolutionary insights. Nat Rev Genet. 2009;10:19\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang Y. Comprehensive catalog processed pseudogenes human mouse. Genome Biol Evol. 2020;12:2730\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVollger MR. Segmental duplications centromere architecture T2T-CHM13 genome. Cell. 2023;186:635\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChaisson MJP, Huddleston J, Dennis MY, Sudmant PH, Malig M, Hormozdiari F, et al. Resolving the complexity of the human genome using single-molecule sequencing. Nature. 2015;517:608\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJain M, Koren S, Miga KH, Quick J, Rand AC, Sasani TA, et al. Nanopore sequencing and assembly of a human genome with ultra-long reads. Nat Biotechnol. 2018;36:338\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBailey JA, Yavor AM, Massa HF, Trask BJ, Eichler EE. Segmental duplications: organization and impact within the current human genome project assembly. Genome Res. 2001;11:1005\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSmits P. Satellite DNA dynamics chromosomal boundaries. Nat Genet. 2023;55:112\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMarques-Bonet T, Eichler EE. burst segmental duplications human lineage. Nat Rev Genet. 2009;10:845\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEichler EE. Genetic variation, comparative genomics, future human evolution. Nat Rev Genet. 2019;20:431\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBailey JA, Gu Z, Clark RA, Reinert K, Samonte RV, Schwartz S, et al. Recent segmental duplications in the human genome. Science. 2002;297:1003\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFeng X. Higher rates processed pseudogene acquisition recently active genomes. Mol Biol Evol. 2021;38:2958\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLinardopoulou EV, Williams EM, Fan Y, Friedman C, Young JM, Trask BJ. Human subtelomeres are hot spots of interchromosomal recombination and segmental duplication. Nature. 2005;437:94\u0026ndash;100.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBailey JA, Eichler EE. Primate segmental duplications: crucibles of evolution, diversity and disease. Nat Rev Genet. 2006;7:552\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHall PA. Septins biology cell division. Nat Rev Mol Cell Biol. 2005;6:451\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFeng Z, Cheng Y. Evolutionary plasticity human subtelomeric duplication blocks. Nat Commun. 2022;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGTEx Consortium. The Genotype-Tissue Expression (GTEx) project. Nat Genet. 2013;45:580\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"mobile-dna","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mdna","sideBox":"Learn more about [Mobile DNA](http://mobilednajournal.biomedcentral.com/)","snPcode":"13100","submissionUrl":"https://submission.nature.com/new-submission/13100/3","title":"Mobile DNA","twitterHandle":"@MobDNAjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Processed pseudogene, Segmental duplication, Telomere-to-telomere assembly, Chromosomal boundary, Retrotransposition, Centromeric duplication, SEPTIN14, Annotation error","lastPublishedDoi":"10.21203/rs.3.rs-7991770/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7991770/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eProcessed pseudogenes arise through LINE-1\u0026ndash;mediated reverse transcription and reintegration of mRNA, a mechanism increasingly recognized as a major force shaping gene evolution. Far from being inert genomic debris, these retrocopies have contributed to gene diversification and regulatory innovation across mammalian lineages. With the completion of telomere-to-telomere (T2T) human genome assemblies, many such loci have been found within duplication-dense pericentromeric and subtelomeric regions. These dynamic chromosomal boundaries frequently undergo recombination and segmental duplication, raising the possibility that an initial retrocopy insertion can act as a structural seed for subsequent DNA-level propagation. Notably, the insertion and duplication of the SEPTIN14 3\u0026prime; terminal exon produced the composite CICP-SEPTIN14P co-mobilized gene unit underlying the CICP pseudogene family. Under current morphology-based annotation systems, such loci are automatically classified as processed pseudogenes, highlighting the limitation of appearance-driven annotation that overlooks mechanistic origin and duplication history.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eThe CICP-SEPTIN14P pair constitutes a co-mobilized gene unit that exemplifies how a processed pseudogene and its parental gene can propagate together as a single duplication block across chromosomal boundaries. Comparative inspection of the GRCh38.p14 and T2T-CHM13v2.0 assemblies identified 28 CICP loci in the human genome, most of which share sequence similarity with SEPTIN14. Approximately two-thirds of these loci are positioned within or adjacent to telomeric, subtelomeric, centromeric, or pericentromeric regions. The putative ancestral copy, CICP12, appears to be a processed pseudogene embedded within the final intron of SEPTIN14, forming the original co-mobilized gene unit that was subsequently propagated to multiple chromosomes through segmental duplication. Sequence alignments revealed extended tracts of \u0026gt;\u0026thinsp;90% identity among pericentromeric and subtelomeric members, supporting a model in which an integrated CICP-SEPTIN14P block was duplicated as a whole rather than generated by independent retrotransposition events. Expression profiling based on GTEx data showed that CICP16 and SEPTIN14P4 display strikingly similar expression patterns across multiple human tissues, suggesting that this co-mobilized duplication unit retained coordinated regulatory behavior after relocation. Comparable tendencies across other CICP-SEPTIN14P pairs reinforce the view that segmentally duplicated, co-mobilized gene units can preserve joint transcriptional control under shared chromatin environments, demonstrating that boundary-linked duplication can maintain regulatory synchrony even after integration into distinct chromosomal contexts.\u003c/p\u003e\u003ch2\u003eConclusions:\u003c/h2\u003e\u003cp\u003eThe CICP-SEPTIN14P co-mobilized gene unit illustrates how a processed pseudogene can transform into a duplication-driven expansion module once integrated near a chromosomal boundary. To avoid systematic misclassification of such loci as independent retrocopies, I propose the Chromosomal Boundary-Associated Processed Pseudogene framework. This model flags any parental gene, pseudogene, or related fragment located within telomeric, subtelomeric, centromeric, or pericentromeric regions and automatically extends the flag to all members of the same gene family for manual review. In addition, I recommend formally recognizing segmentally duplicated processed pseudogenes, defined as processed pseudogenes that later underwent DNA-level block duplication. Together, these measures establish an evolution-aware annotation strategy that integrates chromosomal context into pseudogene classification, offering a framework for improving genome annotation and interpretation in the post-T2T era.\u003c/p\u003e","manuscriptTitle":"The Chromosomal-Boundary Paradox of Processed Pseudogene Annotation in the T2T Era","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-11 07:39:33","doi":"10.21203/rs.3.rs-7991770/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-15T18:47:05+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-14T02:38:55+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-09T06:46:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"318962699630223360635713800197982850553","date":"2025-11-26T03:00:32+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"129122963280477196021969601889671203318","date":"2025-11-12T00:59:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-09T17:51:23+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-03T08:34:38+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-31T14:44:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"Mobile DNA","date":"2025-10-30T17:31:24+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"mobile-dna","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"mdna","sideBox":"Learn more about [Mobile DNA](http://mobilednajournal.biomedcentral.com/)","snPcode":"13100","submissionUrl":"https://submission.nature.com/new-submission/13100/3","title":"Mobile DNA","twitterHandle":"@MobDNAjournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d46f3fef-d463-4e3d-9f9e-0a3ffc52e5ce","owner":[],"postedDate":"November 11th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-23T16:05:56+00:00","versionOfRecord":{"articleIdentity":"rs-7991770","link":"https://doi.org/10.1186/s13100-026-00394-z","journal":{"identity":"mobile-dna","isVorOnly":false,"title":"Mobile DNA"},"publishedOn":"2026-02-17 15:59:10","publishedOnDateReadable":"February 17th, 2026"},"versionCreatedAt":"2025-11-11 07:39:33","video":"","vorDoi":"10.1186/s13100-026-00394-z","vorDoiUrl":"https://doi.org/10.1186/s13100-026-00394-z","workflowStages":[]},"version":"v1","identity":"rs-7991770","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7991770","identity":"rs-7991770","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}