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A molecular approach to estimating the human deleterious mutation rate

✍ Scribed by Alexey S. Kondrashov; James F. Crow

Publisher
John Wiley and Sons
Year
1993
Tongue
English
Weight
515 KB
Volume
2
Category
Article
ISSN
1059-7794

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✦ Synopsis

Human and Department of Genetics, Communicated by Victor A. McKwick

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, pN, with the overall rate of evolution of unique sequence DNA, po. Data on p,N, which are based on pseudogenes, permit an estimate of the total zygotic (twice the genomic) mutation rate, U, = 2pNn = 2(2 x 10-')(3 x lo9) = lo2, where n is the number of nucleotides per genome. Data on po 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 = (pN -p0)/pN and the deleterious zygotic mutation rate, the expected number of new deleterious alleles carried by a zygote, is Us = LJTfs. If fs > 0.01, Us > 1, which would have important implications for human genetics and evolutionary biology.

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