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Why can some genes remain without an assigned function after genome annotation?

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During genome annotation, scientists use bioinformatics to identify candidate genes, often called open reading frames (ORFs), by scanning DNA sequences for specific features like start and stop codons.12

Once these candidates are identified, researchers typically attempt to assign functions by comparing the sequences to known genes in other organisms, relying on the evolutionary conservation of gene sequence and function. However, some genes remain unassigned after this process because their sequences do not sufficiently resemble those of previously characterized genes, making it impossible to deduce their roles through simple comparison. These genes remain without an assigned function until further research, such as functional genomics experiments, can reveal their specific biological roles.21