Nonlinearity in genetic decoding: Homologous DNA replicase genes use alternatives of transcriptional slippage or translational frameshifting

The τ and γ subunits of DNA polymerase III are both encoded by a single gene in Escherichia coli and Thermus thermophilus. γ is two-thirds the size of τ and shares virtually all its amino acid sequence with τ. E. coli and T. thermophilus have evolved very different mechanisms for setting the approximate 1:1 ratio between τ and γ. Both mechanisms put ribosomes into alternate reading frames so that stop codons in the new frame serve to make the smaller γ protein. In E. coli, ≈50% of initiating ribosomes translate the dnaX mRNA conventionally to give τ, but the other 50% shift into the −1 reading frame at a specific site (A AAA AAG) in the mRNA to produce γ. In T. thermophilus ribosomal frameshifting is not required: the dnaX mRNA is a heterogeneous population of molecules with different numbers of A residues arising from transcriptional slippage on a run of nine T residues in the DNA template. Translation of the subpopulation containing nine As (or +/− multiples of three As) yields τ. The rest of the population of mRNAs (containing nine +/− nonmultiples of three As) puts ribosomes into the alternate reading frames to produce the γ protein(s). It is surprising that two rather similar dnaX sequences in E. coli and T. thermophilus lead to very different mechanisms of expression.

Equilibrium distributions of microsatellite repeat length resulting from a balance between slippage events and point mutations

We describe and test a Markov chain model of microsatellite evolution that can explain the different distributions of microsatellite lengths across different organisms and repeat motifs. Two key features of this model are the dependence of mutation rates on microsatellite length and a mutation process that includes both strand slippage and point mutation events. We compute the stationary distribution of allele lengths under this model and use it to fit DNA data for di-, tri-, and tetranucleotide repeats in humans, mice, fruit flies, and yeast. The best fit results lead to slippage rate estimates that are highest in mice, followed by humans, then yeast, and then fruit flies. Within each organism, the estimates are highest in di-, then tri-, and then tetranucleotide repeats. Our estimates are consistent with experimentally determined mutation rates from other studies. The results suggest that the different length distributions among organisms and repeat motifs can be explained by a simple difference in slippage rates and that selective constraints on length need not be imposed.

Somatic mosaicism in Wiskott–Aldrich syndrome suggests in vivo reversion by a DNA slippage mechanism

Somatic mosaicism caused by in vivo reversion of inherited mutations has been described in several human genetic disorders. Back mutations resulting in restoration of wild-type sequences and second-site mutations leading to compensatory changes have been shown in mosaic individuals. In most cases, however, the precise genetic mechanisms underlying the reversion events have remained unclear, except for the few instances where crossing over or gene conversion have been demonstrated. Here, we report a patient affected with Wiskott–Aldrich syndrome (WAS) caused by a 6-bp insertion (ACGAGG) in the WAS protein gene, which abrogates protein expression. Somatic mosaicism was documented in this patient whose majority of T lymphocytes expressed nearly normal levels of WAS protein. These lymphocytes were found to lack the deleterious mutation and showed a selective growth advantage in vivo. Analysis of the sequence surrounding the mutation site showed that the 6-bp insertion followed a tandem repeat of the same six nucleotides. These findings strongly suggest that DNA polymerase slippage was the cause of the original germ-line insertion mutation in this family and that the same mechanism was responsible for its deletion in one of the propositus T cell progenitors, thus leading to reversion mosaicism.

Comparison of California accident rates for single and double tractor-trailer combination trucks. Final report.

Federal Highway Administration, Washington, D.C.

An analysis and investigation of tractor and trailer electrical system capabilities. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Cost and leadtime estimates for improved pillar padding, automatic slack adjusters, visual brake adjustment indicators and tractor/trailer ABS connections. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Incremental cost, weight and leadtime impacts of requiring heavy truck tractor/trailer ABS. Final report.

Mode of access: Internet.

Data analysis of tractor-trailer drivers to access drivers' perception of heavy duty truck ride quality. Final report.

National Highway Traffic Safety Administration, Office of Driver and Pedestrian Research, Washington, D.C.

Development of the agricultural tractor in the United States.

Pt. 2 published without series title or numbering by the American Society of Agricultural Engineers, 1958.

Suggested unit course in farm tractor maintenance ...

"Prepared in cooperation with the United States Office of education."--p. [2] of cover.

Care and operation of the "caterpillar" ... 75 tractor.

Mode of access: Internet.

Operator's organizational, DS, GS, and depot maintenance manual : tractor, full tracked, D.E.D., 7500 lb. min. drawbar pull, w/bulldozer blade, back rip scarifier, J.I. Case model M-450, FSN 2410-935-0714.

"December 1969."

Direct and general support maintenance manual for truck, tractor, line haul, 52,000 GVWR, 6 x 4, M915A2 (NSN 2320-01-272-5029), truck, tractor, light equipment transporter (LET), 68,000 GVWR, 6 x 6 w/winch, M916A1 (NSN 2320-01-272-5028).

"June 1992."