Genome-wide annotation and analyses of bifunctional genes in the human genome

Genome-wide annotation and analyses of bifunctional genes in the human genome | bioRxiv Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search New Results Genome-wide annotation and analyses of bifunctional genes in the human genome View ORCID Profile Janki Insan , View ORCID Profile Manoj B Menon , View ORCID Profile Sonam Dhamija doi: https://doi.org/10.64898/2026.01.28.702170 Janki Insan 1 Kusuma School of Biological Sciences, Indian Institute of Technology Delhi 110016 , India Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Janki Insan Manoj B Menon 1 Kusuma School of Biological Sciences, Indian Institute of Technology Delhi 110016 , India Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Manoj B Menon For correspondence: menon{at}bioschool.iitd.ac.in sdhamija{at}sau.int Sonam Dhamija 2 Faculty of Life Sciences and Biotechnology, South Asian University , New Delhi, 110068, India Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Sonam Dhamija For correspondence: menon{at}bioschool.iitd.ac.in sdhamija{at}sau.int Abstract Full Text Info/History Metrics Supplementary material Preview PDF SUMMARY Conventional gene annotation pipelines classify eukaryotic genes into protein-coding and non-coding. Alternative splicing may generate non-coding transcript variants from protein-coding genes, that are expressed in tissue- or disease- specific manner. We and others have described the genes which transcribe both coding and non-coding transcripts as ‘bifunctional genes’. Here we present a genome-wide analyses of bifunctional genes and reannotate the genes in the human genome reference assembly into coding, non-coding and bifunctional. We identify over 4000 bifunctional genes in the human genome, constituting approximately 10% of the transcribed genes, and present evidence that these genes are conserved in evolution and their number correlate well with genome size and complexity. These genes are enriched in gene sets involved in vesicular transport, autophagy, RNA/DNA binding, glycosylation and splicing. By monitoring the expression of non-coding exons in long-read sequencing datasets and by quantitative RT-PCR, we provide evidence for the expression of non-coding variants from bifunctional genes. The ncRNA transcripts from these genes might have similar or different roles from their cognate mRNA counterparts. They may act as miRNA sponges or harbour non-canonical open-reading frames that encode microproteins, while also competing for binding with RNA-binding proteins. We present evidence for establishing potential biological functions of bifunctional genes and summarise the findings in a searchable database. Further studies and functional characterization focused on this special group of genes may reveal interesting gene regulatory mechanisms relevant to physiology and pathology. Competing Interest Statement The authors have declared no competing interest. Footnotes ↵ 3 Lead contact The text has been revised and additional data added to provide further proof of the expression of non-coding variants from the bifunctional genes Funder Information Declared Department of Biotechnology, https://ror.org/03tjsyq23 , Ramalingaswami Re-entry Fellowship (BT/RLF/Re-entry/10/2019) Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Back to top Previous Next Posted July 21, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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