Cryptic Mutants of Bacteriophage T4

Abstract

HE apparent mutation rate depends upon a number of contingencies: the Tprimary error rate, the probability o€ repair, error avoidance by the apparatus of DNA replication, and the probability of detection. The probability of detection of those base pair substitutions which produce an amino acid substitution appears to be highly variable, and presumably reflects the sensitivity of polypeptide functions to small variations in primary structure.Fine-scale mapping has often revealed a highly nonrandom distribution of mutations among sites. In the T4rZZ system, for instance, 809 of the first 1609 independently isolated mutants were observed to map into only two sites (BEN-ZER 1961). Genetic data indicate that the number of rZZ sites capable of mutation by base pair substitution is about 1700 (EDGAR et al. 1962;STAHL, EDGAR and STEINBERG 1964), and this estimate is supported by quasi-chemical measurements (GOLDBERG 1966). When frameshift mutations are excluded from consideration, however, fewer than 3% of these potential sites have been identified (FREESE 1959;BENZER 1961;ORGEL and BRENNER 1961; see Chapter 5 of DRAKE 1970). What then is the nature of the apparently immutable sites?Two possible answers deserve serious consideration: many sites are extremely weakly mutable, or else many amino acid substitutions are undetected in standard screening systems because they fail to exert significantly deleterious effects upon protein function. The first possibility is supported by the observation that

Addressing Equity Asymmetries in General Chemistry Outcomes Through an Asset-Based Supplemental Course

“…In a study of 32 diverse higher education institutions in the U.S., GC1 was examined as one of three courses with high DFWI 8 rates (the other two were Calculus 1 and Introductory Accounting). 9 According to this study, the DFWI rate nationally for GC1 is 29.4%. Underneath this, however, in examination of overlapping subsets of race and socioeconomic status, white students experience a DFWI rate of 26.3%, female and male students differ with 25.8 and 33.9% DFWI rates.…”

“…Addressing inequities in GC1 is further important because DFW rates in GC1 have a strong relationship with retention, which impacts not only students’ access to future opportunities but also the fiscal health of colleges and universities in the U.S. Higher education institutions in the U.S. are increasingly facing challenges due to demographic changes and declining enrollments, the intensification of revenue losses due to inflation and the COVID-19 emergency, the inability to raise tuition due to competition, and increasing costs from measures taken to control inflation . The national study referenced above found that students who took GC1 and continued at the same institution the following year had a DFW rate of 25.9% in GC1, while GC1-takers who were in good overall academic standing and left the institution within one year of taking GC1 had a DFW rate of 49.2% in GC1 . Thus, as there is a relationship between higher DFW rates in GC1 (nearly double) and leaving the institution, actions that higher education institutions can take to improve equity in GC1 are likely to aid in maintaining enrollment, which benefits an institution’s fiscal health, as well as benefiting the institution’s students and their future careers.…”

“…Students whose STEM degree aspirations are curtailed by being “weeded out” through course outcomes of D or F or withdrawing (termed DFW) in GC1 add this to their accumulated disadvantages. In a study of 32 diverse higher education institutions in the U.S., GC1 was examined as one of three courses with high DFWI rates (the other two were Calculus 1 and Introductory Accounting) . According to this study, the DFWI rate nationally for GC1 is 29.4%.…”

“…12 The national study referenced above found that students who took GC1 and continued at the same institution the following year had a DFW rate of 25.9% in GC1, while GC1-takers who were in good overall academic standing and left the institution within one year of taking GC1 had a DFW rate of 49.2% in GC1. 9 Thus, as there is a relationship between higher DFW rates in GC1 (nearly double) and leaving the institution, actions that higher education institutions can take to improve equity in GC1 are likely to aid in maintaining enrollment, which benefits an institution’s fiscal health, as well as benefiting the institution’s students and their future careers.…”

Chaos and Order in Spontaneous Mutation

“…Or were the missing sites those at which BPSs simply failed to produce a mutant phenotype? This question was addressed experimentally by Bob Koch (Koch and Drake 1970), a brilliant graduate student who was confined to a wheelchair. Starting with two temperature-sensitive rII mutations that had only a slight mutant phenotype at 30°, Bob treated the corresponding mutants with nitrous acid to produce diverse rII transition mutations.…”