  The drift-barrier hypothesis states that random genetic drift constrains the
refinement of a phenotype under natural selection. The influence of effective
population size and the genome-wide deleterious mutation rate were studied
theoretically, and an inverse relationship between mutation rate and genome
size has been observed for many species. However, the effect of the recessive
gene count, an important feature of the genomic architecture, is unknown. In a
Wright-Fisher model, we studied the mutation burden for a growing number of N
completely recessive and lethal disease genes. Diploid individuals are
represented with a binary $2 \times N$ matrix denoting wild-type and mutated
alleles. Analytic results for specific cases were complemented by simulations
across a broad parameter regime for gene count, mutation and recombination
rates. Simulations revealed transitions to higher mutation burden and
prevalence within a few generations that were linked to the extinction of the
wild-type haplotype (least-loaded class). This metastability, that is, phases
of quasi-equilibrium with intermittent transitions, persists over $100\,000$
generations. The drift-barrier hypothesis is confirmed by a high mutation
burden resulting in population collapse. Simulations showed the emergence of
mutually exclusive haplotypes for a mutation rate above 0.02 lethal equivalents
per generation for a genomic architecture and population size representing
complex multicellular organisms such as humans. In such systems, recombination
proves pivotal, preventing population collapse and maintaining a mutation
burden below 10. This study advances our understanding of gene pool stability,
and particularly the role of the number of recessive disorders. Insights into
Muller`s ratchet dynamics are provided, and the essential role of recombination
in curbing mutation burden and stabilizing the gene pool is demonstrated.
