Rates of nucleotide substitution in sexual and anciently asexual rotifers

The class Bdelloidea of the phylum Rotifera is the largest well studied eukaryotic taxon in which males and meiosis are unknown, and the only one for which these indications of ancient asexuality are supported by cytological and molecular genetic evidence. We estimated the rates of synonymous and nonsynonymous substitutions in the hsp82 heat shock gene in bdelloids and in facultatively sexual rotifers of the class Monogononta, employing distance based and maximum likelihood methods. Relative-rate tests, using acanthocephalan rotifers as an outgroup, showed slightly higher rates of nonsynonymous substitution and slightly lower rates of synonymous substitution in bdelloids as compared with monogononts. The opposite trend, however, was seen in intraclass pairwise comparisons. If, as it seems, bdelloids have evolved asexually, an equality of bdelloid and monogonont substitution rates would suggest that the maintenance of sexual reproduction in monogononts is not attributable to an effect of sexual reproduction in limiting the load of deleterious nucleotide substitutions.

The root of the universal tree and the origin of eukaryotes based on elongation factor phylogeny.

The genes for the protein synthesis elongation factors Tu (EF-Tu) and G (EF-G) are the products of an ancient gene duplication, which appears to predate the divergence of all extant organismal lineages. Thus, it should be possible to root a universal phylogeny based on either protein using the second protein as an outgroup. This approach was originally taken independently with two separate gene duplication pairs, (i) the regulatory and catalytic subunits of the proton ATPases and (ii) the protein synthesis elongation factors EF-Tu and EF-G. Questions about the orthology of the ATPase genes have obscured the former results, and the elongation factor data have been criticized for inadequate taxonomic representation and alignment errors. We have expanded the latter analysis using a broad representation of taxa from all three domains of life. All phylogenetic methods used strongly place the root of the universal tree between two highly distinct groups, the archaeons/eukaryotes and the eubacteria. We also find that a combined data set of EF-Tu and EF-G sequences favors placement of the eukaryotes within the Archaea, as the sister group to the Crenarchaeota. This relationship is supported by bootstrap values of 60-89% with various distance and maximum likelihood methods, while unweighted parsimony gives 58% support for archaeal monophyly.

Evolution of chlorophyll and bacteriochlorophyll: the problem of invariant sites in sequence analysis.

Competing hypotheses seek to explain the evolution of oxygenic and anoxygenic processes of photosynthesis. Since chlorophyll is less reduced and precedes bacteriochlorophyll on the modern biosynthetic pathway, it has been proposed that chlorophyll preceded bacteriochlorophyll in its evolution. However, recent analyses of nucleotide sequences that encode chlorophyll and bacteriochlorophyll biosynthetic enzymes appear to provide support for an alternative hypothesis. This is that the evolution of bacteriochlorophyll occurred earlier than the evolution of chlorophyll. Here we demonstrate that the presence of invariant sites in sequence datasets leads to inconsistency in tree building (including maximum-likelihood methods). Homologous sequences with different biological functions often share invariant sites at the same nucleotide positions. However, different constraints can also result in additional invariant sites unique to the genes, which have specific and different biological functions. Consequently, the distribution of these sites can be uneven between the different types of homologous genes. The presence of invariant sites, shared by related biosynthetic genes as well as those unique to only some of these genes, has misled the recent evolutionary analysis of oxygenic and anoxygenic photosynthetic pigments. We evaluate an alternative scheme for the evolution of chlorophyll and bacteriochlorophyll.

Cross-validated maximum likelihood enhances crystallographic simulated annealing refinement

Recently, the target function for crystallographic refinement has been improved through a maximum likelihood analysis, which makes proper allowance for the effects of data quality, model errors, and incompleteness. The maximum likelihood target reduces the significance of false local minima during the refinement process, but it does not completely eliminate them, necessitating the use of stochastic optimization methods such as simulated annealing for poor initial models. It is shown that the combination of maximum likelihood with cross-validation, which reduces overfitting, and simulated annealing by torsion angle molecular dynamics, which simplifies the conformational search problem, results in a major improvement of the radius of convergence of refinement and the accuracy of the refined structure. Torsion angle molecular dynamics and the maximum likelihood target function interact synergistically, the combination of both methods being significantly more powerful than each method individually. This is demonstrated in realistic test cases at two typical minimum Bragg spacings (dmin = 2.0 and 2.8 Å, respectively), illustrating the broad applicability of the combined method. In an application to the refinement of a new crystal structure, the combined method automatically corrected a mistraced loop in a poor initial model, moving the backbone by 4 Å.

Training and search methods for speech recognition.

Speech recognition involves three processes: extraction of acoustic indices from the speech signal, estimation of the probability that the observed index string was caused by a hypothesized utterance segment, and determination of the recognized utterance via a search among hypothesized alternatives. This paper is not concerned with the first process. Estimation of the probability of an index string involves a model of index production by any given utterance segment (e.g., a word). Hidden Markov models (HMMs) are used for this purpose [Makhoul, J. & Schwartz, R. (1995) Proc. Natl. Acad. Sci. USA 92, 9956-9963]. Their parameters are state transition probabilities and output probability distributions associated with the transitions. The Baum algorithm that obtains the values of these parameters from speech data via their successive reestimation will be described in this paper. The recognizer wishes to find the most probable utterance that could have caused the observed acoustic index string. That probability is the product of two factors: the probability that the utterance will produce the string and the probability that the speaker will wish to produce the utterance (the language model probability). Even if the vocabulary size is moderate, it is impossible to search for the utterance exhaustively. One practical algorithm is described [Viterbi, A. J. (1967) IEEE Trans. Inf. Theory IT-13, 260-267] that, given the index string, has a high likelihood of finding the most probable utterance.

A maximum likelihood algorithm for genome mapping of cytogenetic loci from meiotic configuration data.

Frequencies of meiotic configurations in cytogenetic stocks are dependent on chiasma frequencies in segments defined by centromeres, breakpoints, and telomeres. The expectation maximization algorithm is proposed as a general method to perform maximum likelihood estimations of the chiasma frequencies in the intervals between such locations. The estimates can be translated via mapping functions into genetic maps of cytogenetic landmarks. One set of observational data was analyzed to exemplify application of these methods, results of which were largely concordant with other comparable data. The method was also tested by Monte Carlo simulation of frequencies of meiotic configurations from a monotelodisomic translocation heterozygote, assuming six different sample sizes. The estimate averages were always close to the values given initially to the parameters. The maximum likelihood estimation procedures can be extended readily to other kinds of cytogenetic stocks and allow the pooling of diverse cytogenetic data to collectively estimate lengths of segments, arms, and chromosomes.