Kondrashov A S, Crow J F
Institute of Mathematical Problems of Biology, Pushchino, Moscow Region, Russia.
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.
我们提出了一种基于每代每个核苷酸中性序列的进化速率（微N）与独特序列DNA的总体进化速率（微O）的比较来测量人类基因组有害突变率的方法。基于假基因的微N数据可以估算总合子（基因组的两倍）突变率，UT = 2微Nn = 2(2×10⁻⁸)(3×10⁹) ≈ 10²，其中n是每个基因组中的核苷酸数量。微O的数据可以通过比较来自人类和相关物种基因组的相对较短同源序列的代表性样本获得。受负选择控制的基因组部分为fS =（微N - 微O）/微N，而有害合子突变率，即合子携带的新有害等位基因的预期数量，为US = UTfS。如果fS > 0.01，US > 1，这将对人类遗传学和进化生物学产生重要影响。
