Hidden breakpoints in genome alignments

During the course of evolution, an organism's genome can undergo changes that affect the large-scale structure of the genome. These changes include gene gain, loss, duplication, chromosome fusion, fission, and rearrangement. When gene gain and loss occurs in addition to other types of rearrangement, breakpoints of rearrangement can exist that are only detectable by comparison of three or more genomes. An arbitrarily large number of these "hidden" breakpoints can exist among genomes that exhibit no rearrangements in pairwise comparisons. We present an extension of the multichromosomal breakpoint median problem to genomes that have undergone gene gain and loss. We then demonstrate that the median distance among three genomes can be used to calculate a lower bound on the number of hidden breakpoints present. We provide an implementation of this calculation including the median distance, along with some practical improvements on the time complexity of the underlying algorithm. We apply our approach to measure the abundance of hidden breakpoints in simulated data sets under a wide range of evolutionary scenarios. We demonstrate that in simulations the hidden breakpoint counts depend strongly on relative rates of inversion and gene gain/loss. Finally we apply current multiple genome aligners to the simulated genomes, and show that all aligners introduce a high degree of error in hidden breakpoint counts, and that this error grows with evolutionary distance in the simulation. Our results suggest that hidden breakpoint error may be pervasive in genome alignments.Comment: 13 pages, 4 figure

Two new portable survey instruments: the field phoswich detector and the Wee Pee Pee

As part of a continuing program to upgrade the health physics survey instrumentation at Los Alamos, we have recently developed two new portable instruments. The first is a fully portable phoswich detector for low energy photons from small amounts of plutonium and americium in the field. The instrument has a background that is 2 to 3 times lower than an equivalent thin NaI detector. The instrument features an aural popper, analogue rate meter, and timer/scaler with liquid crystal display. The second instrument, called the ''Wee Pee Wee,'' is an alpha air proportional probe with complete electronics and readout package mounted on the probe itself. The entire package has a mass of 0.66 kg (1.45 lb) and is carried and operated in one hand. For monitoring shoes and other places where it is difficult to read the count-rate meter, the meter is made detachable for clipping to a shirt pocket, etc. An audio popper, range scales to 100 K cpm, and visual checks for high voltage and battery levels are also included

Optimal design of feedback control by inhibition

The local stability of unbranched biosynthetic pathways is examined by mathematical analysis and computer simulation using a novel nonlinear formalism that appears to accurately describe biochemical systems. Four factors affecting the stability are examined: strength of feedback inhibition, equalization of the values among the corresponding kinetic parameters for the reactions of the pathway, pathway length, and alternative patterns of feedback interaction. The strength of inhibition and the pattern of feedback interactions are important determinants of steady-state behavior. The simple pattern of end-product inhibition in unbranched pathways may have evolved because it optimizes the steady-state behavior and is temporally most responsive to change. Stability in these simple systems is achieved by shortening pathway length either physically or, in the case of necessarily long pathways, kinetically by a wide divergence in the values of the corresponding kinetic parameters for the reactions of the pathway. These conclusions are discussed in the light of available experimental evidence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/48053/1/239_2005_Article_BF01741242.pd