Genomic Rate of Recessive Lethal Mutations in Danio rerio

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9981445WhitlockThe goals of this project are to measure in the zebrafish, a vertebrate model organism: (1) the number of recessive lethals (an extreme kind of harmful mutation) in the genome and (2) the rate that such harmful mutations arise. The number of lethal mutations carried in the genome will be estimated by measuring the fraction of lethal-free offspring that are produced using a new technique that makes individuals have only a single copy of the genome and so express all lethal mutations. The rate at which lethal mutations arise will be measured by making individuals in which both copies of the genome are identical (and thus carry no recessive lethals) and then measuring the number of lethals that arise in the next generation. This study will provide the first data in any vertebrate on the genomic rate at which new harmful mutations arise. Among animals, data on the genomic rate of the new appearance of harmful mutations is available only for fruit flies. Knowledge of the rate that harmful mutations arise is essential to understanding evolutionary processes in living organisms, in managing small populations of endangered animals, as well as in assessing health risks in humans. While it is known that an average human newborn carries ~100 de novo mutations, it is not clear what fraction of them are harmful and so might contribute to miscarriage and a variety of hereditary diseases.