Charles H. Langley

An examination of the constancy of the rate of molecular evolution

SummaryThe vertebrate evolution of four proteins (6 andβ hemoglobins, cytochromec, and fibrinopeptide A) is examined via a maximum likelihood procedure. The fundamental hypothesis is that the process of nucleotide substitution as revealed by the minimum phyletic distance procedure (Fitch, 1971) is Poisson with a constant time average for each protein. The method allows the simultaneous estimation of the relative times of divergence of all common ancestors while utilizing the information from all four proteins. It also affords the possibility of statistically testing several biologically meaningful hypotheses. The results are the following: 1.The total rate (sum of all proteins) of nucleotide substitution is not constant in time throughout the evolution of vertebrates.2.The relative rates (among proteins) of nucleotide substitution are not constant throughout vertebrate evolution.3.Despite the variation in the rates of nucleotide substitution the procedure employed provides estimates of the relative time of divergence which correlate well with paleontological dates.4.The overall rate of nucleotide substitution within the primates is again found to be less than the rest of the mammals.

On the role of unequal exchange in the containment of transposable element copy number

A population genetics model of the role of asymmetric pairing and unequal exchange in the stabilization of transposable element copy number in natural populations is proposed and analysed. Monte Carlo simulations indicate that the approximations incorporated into the analysis are robust in the relevant parameter ranges. Given several simple assumptions concerning transposition and excision, equal and unequal exchange, and chromosome structure, predictions of the relative numbers of transposable elements in various regions of the Drosophila melanogaster genome are compared to the observed distribution of roo / B104 elements across chromosomal regions with differing rates of exchange, and between X chromosomes and autosomes. There is no indication of an accumulation of elements in the distal regions of chromosomes, which is expected if unequal exchange is reduced concomitantly with normal crossing over in the distal regions. There is, however, an indication of an excess of elements relative to physical length in the proximal regions of the chromosomes, which also have restricted crossing over. This observation is qualitatively consistent with the models predictions. The observed distribution of elements between the mid-sections of the X chromosomes and autosomes is consistent with the predictions of one of two models of unequal exchange.

Are evolutionary rates really variable

SummaryLangley and Fitch (1974, 1976) have shown that the pattern of nucleotide substitutions in proteins is inconsistent with a Poisson process with constant rate. From this they conclude that the rate is temporally heterogeneous. It is pointed out in this note that a process which is temporally homogeneous but not a Poisson process is compatible with the data if the coefficient of variation of the time between substitutions is around 1.63. Furthermore, theoretical analysis of samples from neutral phylogenies shows that these samples should not appear to be samples from a Poisson process, but should deviate from a Poisson process in the same direction, though perhaps not to the same extent, as do the data.

Retrovirus-like features and site specific insertions of a transposable element, tom, in Drosophila ananassae

SummaryThe tom element, putatively associated with optic morphology (Om) mutations in Drosophila ananassae, was identified as a retrovirus-like transposable element. The tom element was found to terminate with 475 (or 474) base pair direct repeats which are identical in sequence to each other. Southern blot and heteroduplex analyses showed the tom element to have high homology to 297 and 17.6, two retrotransposons found in D. melanogaster. As in the cases of 297 and 17.6, tom includes nucleotide sequences coding for a presumptive protease and reverse transcriptase, similar in amino acid sequence to those of the Moloney murine leukaemia virus. At the tom insertion site of the sn9g locus, a host DNA sequence (T)ATAT was found to be duplicated on each side of the tom insertion and all other tom elements examined were also flanked by (T)ATAT. In each of six cases, the 5′ flanking host sequence was TATAT. These results indicate that the target sequence of the tom element may be TATAT and that the entire region or a part of this sequence was duplicated on insertion of the tom element.

Genetic analysis of protein variations in Mus musculus using two-dimensional electrophoresis

We have investigated the variation of proteins from crude homogenates of mouse kidneys in several strains of Mus musculus by means of two-dimensional electrophoresis. In this study, we have used the strains C57BL/6J, DBA/2J, CD-1, M. m. castaneus, and M. m. molossinus, as well as offspring from crosses among these strains. Out of the 100 loci screened, we have found nine loci showing interstrain differences. We have been able to identify three proteins as Id-1, Car-2, and Sep-1. The remaining variants are probably new loci in the mouse. Most of the variants (seven) can be mapped to a chromosome. We have found also that differences in the protein pattern as seen on two-dimensional gels are small among subspecies of Mus musculus.

Analysis of linkage disequilibria between allozyme loci in natural populations of Drosophila melanogaster

Linkage disequilibria between pairs of 8 polymorphic enzyme loci (aGpdh, Mdh, Adh, Est-6, Pgm, Odh, Est-C and Acph) in some 100 natural population samples of Drosophila melanogaster were examined. The estimates of linkage disequilibrium were made from zygotic frequencies. The magnitude of linkage disequilibria are small and similar to those in previous reports. Variation in linkage disequilibrium among related subpopulations was analysed by analysis of variance of the correlation coefficients. Despite the small absolute value of linkage disequilibrium there is a suggestion of a correlation among related subpopulations. The magnitude of linkage disequilibrium was observed to be positively correlated with linkage. Two cage populations were observed to demonstrate large amounts of linkage disequilibrium between closely linked loci in contrast to the situation in natural populations. This is attributable to the finite sizes of these cage populations.

Evolutionary Rates in Proteins: Neutral Mutations and the Molecular Clock

There is an interesting relationship between neutral mutations and the molecular clock. The theory of neutral mutations requires that the rate of fixation of a mutation be equal to the neutral mutation rate. Thus the fixation of neutral mutations should be clocklike, with each “tick” of the clock representing another fixation. Naturally the clock will not be metronomic but, like a radioactive clock, stochastic, with fixation events in the unit time interval showing a Poisson distribution. Although a test of the clock hypothesis is a test of the neutral hypothesis, the existence of a clock does not depend on the correctness of the neutral hypothesis (see also Sarich and Cronin, this volume). This has resulted in past confusion. In a similar fashion, the covarion (concomitantly variable codons) concept (Fitch and Markowitz, 1970) is also independent of the correctness of the neutral hypothesis. We shall consider in turn a statistical model to test evolutionary rates, the results of that test, a comparison of our estimated rates with those from other sources, and some problems in testing evolutionary clocks.

Purification and molecular weight determination of glucose-6-phosphate dehydrogenase and malic enzyme from mouse and Drosophila

Abstract A facile two-step procedure was employed for simultaneous purification of glucose-6-phosphate dehydrogenase and malic enzyme from mouse (strain DBA 2J ) and Drosophila melanogaster. This involved the use of an 8-(6-aminohexyl)-amino-2′,5′-ADP-Sepharsoe affinity column chromatography followed by DEAE-Sephadex chromatography. The native and subunit molecular weights of these two homogeneous enzymes were determined by gel-filtration chromatography and SDS-polyacrylamide gel electrophoresis. From this study, it was concluded that the two enzymes are tetrameric and have native molecular weights between 200,000 and 280,000 in both species.

A new estimate of sequence divergence of mitochondrial DNA using restriction endonuclease mappings.

SummaryA new estimate of the sequence divergence of mitochondrial DNA in related species using restriction enzyme maps is constructed. The estimate is derived assuming a simple Posisson-like model for the evolutionary process and is chosen to maximize an expression which is a reasonable approximation to the true likelihood of the restriction map data. Using this estimate, four sets of mitochondrial DNA data are analyzed and discussed.

Genetic and cytogenetic studies of four glycolytic enzymes in Drosophila melanogaster: Aldolase, triosephosphate isomerase, 3-phosphoglycerate kinase, and phosphoglucomutase

Four glycolytic enzymes in Drosophila melanogaster have been genetically and/or cytogenetically mapped. The structural gene for aldolase (Ald) has been genetically mapped to 3-91.5 and cytogenetically localized to 97A-B. Tpi, the structural gene for triosephosphate isomerase, has been genetically mapped to 3-101.3 and cytogenetically localized to 99B-E. Utilizing closer-flanking markers than the previous mapping, Pgk, the structural gene for 3-phosphoglycerate kinase, has been mapped to 2-5.9; cytogenetically it was found to lie in the interval between 22D and 23E3. The cytogenetic location of Pgm, the structural gene for phosphoglucomutase which has been located genetically at 3-43.4, was determined to be in 72D1-5.