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M Nei

Publications and source records attributed to M Nei.

At least 37 records · Page 2Linked to original sources

Phylogenetic analysis of polymorphic DNA sequences at the Adh locus in Drosophila melanogaster and its sibling species.

Recent sequencing of over 2300 nucleotides containing the alcohol dehydrogenase (Adh) locus in each of 11 Drosophila melanogaster lines makes it possible to estimate the approximate age of the electrophoretic "fast-slow" polymorphism. Our estimates, based on various possible patterns of evolution, range from 610,000 to 3,500,000 years, with 1,000,000 years as a reasonable point estimate. Furthermore, comparison of these sequences with those of the homologous region of D. simulans and D. mauritiana allows us to infer the pattern of evolutionary change of the D. melanogaster sequences. The integrity of the Adh-f electrophoretic alleles as a single lineage is supported by both unweighted pair-group method (UPGMA) and parsimony analyses. However, considerable divergence among the Adh-s lines seems to have preceded the origin of the Adh-f allele. Comparisons of the sequences of D. melanogaster genes with those of D. simulans and D. mauritiana genes suggest that the split between the latter two species occurred more recently than the divergence of some of the present-day Adh-s genes in D. melanogaster. The phylogenetic analyses of the D. melanogaster sequences show that the fast-slow distinction is not perfect, and suggest that intragenic recombination or gene conversion occurred in the evolution of this locus. We extended conventional phylogenetic analyses by using a statistical technique for detecting and characterizing recombination events. We show that the pattern of differentiation of DNA sequences in D. melanogaster is roughly compatible with the neutral theory of molecular evolution.

Alcohol Dehydrogenase

Methods for computing the standard errors of branching points in an evolutionary tree and their application to molecular data from humans and apes.

Statistical methods for computing the standard errors of the branching points of an evolutionary tree are developed. These methods are for the unweighted pair-group method-determined (UPGMA) trees reconstructed from molecular data such as amino acid sequences, nucleotide sequences, restriction-sites data, and electrophoretic distances. They were applied to data for the human, chimpanzee, gorilla, orangutan, and gibbon species. Among the four different sets of data used, DNA sequences for an 895-nucleotide segment of mitochondrial DNA (Brown et al. 1982) gave the most reliable tree, whereas electrophoretic data (Bruce and Ayala 1979) gave the least reliable one. The DNA sequence data suggested that the chimpanzee is the closest and that the gorilla is the next closest to the human species. The orangutan and gibbon are more distantly related to man than is the gorilla. This topology of the tree is in agreement with that for the tree obtained from chromosomal studies and DNA-hybridization experiments. However, the difference between the branching point for the human and the chimpanzee species and that for the gorilla species and the human-chimpanzee group is not statistically significant. In addition to this analysis, various factors that affect the accuracy of an estimated tree are discussed.

Amino Acid Sequence

Evolutionary change of restriction cleavage sites and phylogenetic inference for man and apes.

A mathematical theory for the evolutionary change of restriction endonuclease cleavage sites is developed, and the probabilities of various types of restriction-site changes are evaluated. A computer simulation is also conducted to study properties of the evolutionary change of restriction sites. These studies indicate that parsimony methods of constructing phylogenetic trees often make erroneous inferences about evolutionary changes of restriction sites unless the number of nucleotide substitutions per site is less than 0.01 for all branches of the tree. This introduces a systematic error in estimating the number of mutational changes for each branch and, consequently, in constructing phylogenetic trees. Therefore, parsimony methods should be used only in cases where nucleotide sequences are closely related. Reexamination of Ferris et al.'s data on restriction-site differences of mitochondrial DNAs does not support Templeton's conclusions regarding the phylogenetic tree for man and apes and the molecular clock hypothesis. Templeton's claim that Nei and Li's method of estimating the number of nucleotide substitutions per site is seriously affected by parallel losses and loss-gains of restriction sites is also unsupported.

Animals

Mathematical model for studying genetic variation in terms of restriction endonucleases.

A mathematical model for the evolutionary change of restriction sites in mitochondrial DNA is developed. Formulas based on this model are presented for estimating the number of nucleotide substitutions between two populations or species. To express the degree of polymorphism in a population at the nucleotide level, a measure called "nucleotide diversity" is proposed.

Base Sequence

Nonrandom amino acid substitution and estimation of the number of nucleotide substitutions in evolution.

A method of estimating the number of nucleotide substitutions from amino acid sequence data is developed by using Dayhoff's mutation probability matrix. This method takes into account the effect of nonrandom amino acid substitutions and gives an estimate which is similar to the value obtained by Fitch's counting method, but larger than the estimate obtained under the assumption of random substitutions (Jukes and Cantor's formula). Computer simulations based on Dayhoff's mutation probability matrix have suggested that Jukes and Holmquist's method of estimating the number of nucleotide substitutions gives an overestimate when amino acid substitution is not random and the variance of the estimate is generally very large. It is also shown that when the number of nucleotide substitutions is small, this method tends to give an overestimate even when amino acid substitution is purely at random.

Amino Acid Sequence

Goodman et al.'s method for augmenting the number of nucleotide substitutions.

Statistical properties of Goodman et al.'s (1974) method of compensating for undetected nucleotide substitutions in evolution are investigated by using computer simulation. It is found that the method tends to overcompensate when the stochastic error of the number of nucleotide substitutions is large. Furthermore, the estimate of the number of nucleotide substitutions obtained by this method has a large variance. However, in order to see whether this method gives overcompensation when applied together with the maximum parsimony method, a much larger scale of simulation seems to be necessary.

Biological Evolution

Subunit molecular weight and genetic variability of proteins in natural populations.

The relationship between subunit molecular weight and heterozygosity was studied in six different groups of organisms, i.e., 9 species of primates, 32 species of rodents, 56 species of reptiles, 12 species of salamanders, 64 species of teleost fishes, and 29 species of Drosophila. The correlation coefficient between them was positive in all groups, and the magnitude of correlation was roughly in agreement with the theoretical expectation under the mutation-drift hypothesis when the incomplete correlation between molecular weight and mutation rate was taken into account. Furthermore, the correlation was higher when the average heterozygosity was high than when this was low, as theoretically expected.

Gene Frequency

Standard error of immunological dating of evolutionary time.

The empirical variance of the immunological distance as measured by microcomplement fixation with albumin is determined. The variance obtained is at least two times larger than the mean when the mean is small and the ratio of the variance to the mean increases with increasing mean. Thus, the immunological dating of evolutionary time has a large standard error. It is shown that in bird lysozymes the relationship between immunological distance (y) and the number of amino acid substitutions per 100 sites (x) is given by y = 4.2 x approximately.

Amino Acid Sequence

Persistence of common alleles in two related populations or species.

Mathematical studies are conducted on three problems that arise in molecular population genetics. (1) The time required for a particular allele to become extinct in a population under the effects of mutation, selection, and random genetic drift is studied. In the absence of selection, the mean extinction time of an allele with an initial frequency close to 1 is of the order of the reciprocal of the mutation rate when 4Nv less than 1, where N is the effective population size and v is the mutation rate per generation. Advantageous mutations reduce the extinction time considerably, whereas deleterious mutations increase it tremendously even if the effect on fitness is very slight. (2) Mathematical formulae are derived for the distribution and the moments of extinction time of a particular allele from one or both of two related populations or species under the assumption of no selection. When 4Nv less than 1, the mean extinction time is about half that for a single population, if the two populations are descended from a common original stock. (3) The expected number as well as the proportion of common neutral alleles shared by two related species at the tth generation after their separation are studied. It is shown that if 4Nv is small, the two species are expected to share a high proportion of common alleles even 4N generations after separation. In addition to the above mathematical studies, the implications of our results for the common alleles at protein loci in related Drosophila species and for the degeneration of unused characters in cave animals are discussed.

Alleles

F-statistics and analysis of gene diversity in subdivided populations.

It is show that Wright's F-statistics can be defined as ratios of gene diversities of heterozygosities rather than as the correlations of uniting gametes. This definition is applicable irrespective of the number of alleles involved or whether there is selection or not. The relationship between F-statistics and Nei's gene diversity analysis is discussed.

Alleles

Estimation of mutation rate from rare protein variants.

A method for estimating the mutation rate for protein loci from the number of rare alleles in the population is presented. It seems to have a number of advantages compared with Kimura and Ohta's method. Applying this method to Neel's data from American Indians in South America and to Nozawa's data from Japanese macaques, the mutation rate for electrophoretically detectable alleles is estimated to be (2 approximately 3) x 10(-6) per locus per generation. This estimate may not include many severely or substantially deleterious mutations.

Alleles

Statistical studies on protein polymorphism in natural populations. I. Distribution of single locus heterozygosity.

Surveying the literature, the frequency distribution of single-locus heterozygosity among protein loci was examined in 95 vertebrate and 34 invertebrate species with the aim of testing the validity of the mutation-drift hypothesis. This distribution did not differ significantly from that expected under the mutation-drift hypothesis for any of the species examined when tested by the Kolmogorov-Smirnov goodness-of-fit statistic. The agreement between the observed interlocus variance of heterozygosity and its theoretical expectation was also satisfactory. There was an indication that variation in the mutation rate among loci inflates the interlocus variance of heterozygosity. The variance of heterozygosity for a homologous locus among different species was also studied. This variance generally agreed with the theoretical value very well, though in some groups of Drosophila species there was a significant discrepancy. The observed relationship between average heterozygosity and the proportion of polymorphic loci was in good agreement with the theoretical relationship. It was concluded that, with respect to the pattern of distribution of heterozygosity, the majority of data on protein polymorphisms are consistent with the mutation-drift hypothesis. After examining alternative possible explanations involving selection, it was concluded that the present data cannot be explained adequately without considering a large effect of random genetic drift, whether there is selection or not.

Animals

Electrophoretically silent alleles in a finite population.

The expected number of silent alleles in an electromorph is computed for various values of population size (N), mutation rate (u), and sample size (s) under the assumption of no selection. The proportion of alleles undetectable by electrophoresis is higher when Nu is large than when this is small. It is shown that an electromorph of high population frequency has more silent alleles than an electromorph of low frequency if the sample size is the same.

Alleles