A molecular approach to estimating the human deleterious mutation rate

Hum Mutat. 1993;2(3):229-34. doi: 10.1002/humu.1380020312.


We propose a method of measuring the human genomic deleterious mutation rate based on comparison of the rate of evolution per nucleotide per generation of neutral sequences, microN, with the overall rate of evolution of unique sequence DNA, microO. Data on microN, which are based on pseudogenes, permit an estimate of the total zygotic (twice the genomic) mutation rate, UT = 2 microNn = 2(2 x 10(-8)(3 x 10(9)) approximately 10(2), where n is the number of nucleotides per genome. Data on microO can be obtained by comparison of representative samples of relatively short homologous sequences from the genomes of Homo and a related species. The fraction of the genome that is controlled by negative selection is fS = (microN - microO)/microN and the deleterious zygotic mutation rate, the expected number of new deleterious alleles carried by a zygote, is US = UTfS. If fS > 0.01, US > 1, which would have important implications for human genetics and evolutionary biology.

MeSH terms

  • Biological Evolution
  • DNA Mutational Analysis / methods*
  • Genes, Lethal
  • Genetics, Medical
  • Genome, Human*
  • Humans
  • Mutation*