Mutational Fitness Effects in Recent Genomic Studies

Living genomes are continuously exposed to a myriad of copying errors, chemical lesions, and replication slippage that can impact fitness and modulate population-level outcomes. However, robust experimental methods have faithfully revealed the scope of this damage by either direct competition assays or multi-generational tracking across yeast, humans, birds, fish, and plants. Deviations in the expected neutral fraction are now known to destabilize traditional theoretical frameworks, as exemplified in studies by Shen (2022), Matheson (2023), and Chen et al. (2025) where 70 to 80 percent of mutations proved deleterious. Because these convergent findings pose quantitative challenges that current models have not fully reconciled, testing their implications across taxa and methods has become important. In this review, we delineate the empirical measurements, theoretical responses, and molecular constraints to provide insights into why the mutational landscape is dominated by damage rather than innovation.