ORIGIN OF MUTATIONS

On the origin of deleterious mutations.

Deleterious mutations and the origin of the meiotic ploidy cycle.

A population genetical model is investigated in which the organism either alternates between diploid and haploid states or lives entirely in the haploid state. The behavior of the organism is determined by the genotype at a modifier locus. At an independent locus deleterious mutations occur at a low but constant frequency. It is found that the haploid behavior is always an evolutionarily attain...

The Origin and Evolution of Mutations in Acute Myeloid Leukemia

Most mutations in cancer genomes are thought to be acquired after the initiating event, which may cause genomic instability and drive clonal evolution. However, for acute myeloid leukemia (AML), normal karyotypes are common, and genomic instability is unusual. To better understand clonal evolution in AML, we sequenced the genomes of M3-AML samples with a known initiating event (PML-RARA) versus...

The origin of point mutations in human tumor cells.

The idea that point mutation is central to carcinogenesis is an old one (e.g. Ref. l). Until recently, however, specific genetic changes had not been observed in tumors and a keystone of the belief that genetic change is central to carcinogenesis was what appeared to be a close correlation between mutagenicity and carcinogenicity (2). The situation is almost completely reversed today. The class...

Origin of mutations under selection: the adaptive mutation controversy.

Growth under selection causes new genotypes to predominate in a population. It is difficult to determine whether selection stimulates formation of new mutations or merely allows faster growth of mutants that arise independent of selection. In the practice of microbial genetics, selection is used to detect and enumerate pre-existing mutants; stringent conditions prevent growth of the parent and ...