The Dark Genome Investigating Pseudogenes and Non-Coding Regions in Genetic Regulation

The "dark genome," comprising pseudogenes and various non-coding DNA elements, has historically been overlooked due to the assumption of its non-functionality. Recent advances in genomics and epigenetics have overturned this view, revealing that these sequences play crucial roles in genetic regulation, development, disease, and evolution. Pseudogenes, once dismissed as evolutionary relics, are now recognized for their regulatory potential via RNA interference, decoy functions, and epigenetic modulation. Non-coding regions such as long non-coding RNAs (lncRNAs), enhancer RNAs (eRNAs), and other untranslated elements contribute to transcriptional control and chromatin architecture. This review explores the biological functions of these components, their implications in health and disease, and their growing relevance in biomedical research. Furthermore, we examine how emerging technologies such as single-cell sequencing, CRISPR-based editing, and integrative multi-omics are shedding light on the regulatory functions of the dark genome. Despite significant progress, many challenges persist, including functional validation, annotation inconsistency, and interpretation of non-coding variants. This paper aims to synthesize current findings, highlight biomedical applications, discuss limitations, and propose future research directions, emphasizing the need to embrace the dark genome for a more comprehensive understanding of gene regulation and genome complexity.