Quartet-mapping, a generalization of the likelihood-mapping procedure.

Likelihood-mapping (LM) was suggested as a method of displaying the phylogenetic content of an alignment. However, statistical properties of the method have not been studied. Here we analyze the special case of a four-species tree generated under a range of evolution models and compare the results with those of a natural extension of the likelihood-mapping approach, geometry-mapping (GM), which is based on the method of statistical geometry in sequence space. The methods are compared in their abilities to indicate the correct topology. The performance of both methods in detecting the star topology is especially explored. Our results show that LM tends to reject a star tree more often than GM. When assumptions about the evolutionary model of the maximum-likelihood reconstruction are not matched by the true process of evolution, then LM shows a tendency to favor one tree, whereas GM correctly detects the star tree except for very short outer branch lengths with a statistical significance of >0.95 for all models. LM, on the other hand, reconstructs the correct bifurcating tree with a probability of >0.95 for most branch length combinations even under models with varying substitution rates. The parameter domain for which GM recovers the true tree is much smaller. When the exterior branch lengths are larger than a (analytically derived) threshold value depending on the tree shape (rather than the evolutionary model), GM reconstructs a star tree rather than the true tree. We suggest a combined approach of LM and GM for the evaluation of starlike trees. This approach offers the possibility of testing for significant positive interior branch lengths without extensive statistical and computational efforts.

Identification of a novel mouse Iroquois homeobox gene, Irx5, and chromosomal localisation of all members of the mouse Iroquois gene family.

The Drosophila genes of the Iroquois-Complex encode homeodomain containing transcription factors that positively regulate the activity of certain proneural Achaete/Scute-C (AS-C) genes during the formation of external sensory organs (J. L. Gomez-Skarmeta and J. Modolell, EMBO J 17:181-190, 1996). Previously, we have identified three highly-related genes of the mouse Iroquois gene family that exert specific expression patterns in the central nervous system (A. Bosse et al., Mech Dev 69:169-181, 1997). In the present paper, we report the identification of a novel member of the Iroquois gene family, Irx5, that shows a restricted spatio/temporal expression during early mouse embryogenesis, distinct from the expression of Irx1-3. An extensive sequence analysis of 20 Iroquois-like genes from seven organisms reveals a high conservation of the homeodomain. Phylogenetic tree reconstruction showed a clustering of the members of the Iroquois gene family into groups of orthologous genes. Together, with the data obtained from the chromosomal mapping analysis, the results indicate that these genes have appeared in vertebrates during evolution as a result of gene duplication.

The emergence of genetic coding in physical systems.

A simple model of molecular biological translation, based on the classification of polymers as either information carriers or functional catalysts, is used to analyse formal constraints on physical systems which utilise genetic coding. We investigate (i) how the structure-function relationship for coding assignment catalysts constrains the selection of genetic information which can sustain functional self-organisation and (ii) what general prerequisites must be satisfied for selection to give rise to an increase in functional complexity. This is done by considering two separate alphabets and defining the complete set of assignments from letters of one alphabet onto letters from the other. A code is defined as a set of assignments which maps each letter from the first alphabet onto a letter from the second alphabet. We enumerate all the embeddings of the assignment functions in the minimal sequence space of strings of letters from the second alphabet and demonstrate how the embeddings can be classified according to whether they allow different codes to be represented unambiguously in the minimal sequence space of strings of letters from the first alphabet. Non-minimal embeddings are also discussed. Finally, we consider how the mutual specification of letters of the two alphabets and assignment functions can be decomposed into more highly differentiated classes. Only a certain class of embeddings allows coding to be preserved under decomposition. We conclude that the evolution of increasing coding complexity can take place only when special conditions are satisfied regarding the structure-function relationship for the coding assignment catalysts.

Graphs in sequence spaces: a review of statistical geometry.

Statistical geometry is a method of comparative sequence analysis of genes. Based on the concept of the sequence space of nucleic acids it computes the geometries of sequence sets, mainly quartets, by combining both the vertical and horizontal information content of the sequences. The geometries can be used to deduce, for example, the degree of tree-likeness of the data set without any a priori assumption of an evolution model. Furthermore, statistical geometry allows to detect varying positional substitution rates in sequences. Applications of the method to tRNA sequences have provided an assessment for the age of the genetic code. Furthermore, applications of statistical geometry to homeoboxes as well as different virus families have helped to assign reliable kinship relationships. In addition, a lower bound for the age of the common ancestor of the human and simian immunodeficiency viruses has been established.

Genetic drift can dominate short-term human immunodeficiency virus type 1 nef quasispecies evolution in vivo.

The evolution of human immunodeficiency virus (HIV) type 1 nef quasispecies in a patient clonally infected with a contaminated batch of blood clotting factor IX was monitored. nef sequences were derived at 11, 25, and 41 months postinfection from infected peripheral blood mononuclear cells after molecular cloning of PCR-amplified proviral DNA. The phylogenetic relationships among a total of 41 informative sequences were established by split decomposition analysis and used as a basis to establish a substitution matrix and to score synonymous (s) and nonsynonymous (ns) substitutions. The number of observed in-phase stop codons within the nef sequences was comparable to that expected on a random basis. Similarly, the numbers of observed s and ns substitutions did not differ significantly from expected values. No codon position was preferentially mutated. The maximum sequence divergence increased in a linear manner, with approximately 4.4 nucleotide and approximately 3.2 amino acid changes per year. It appears that stochastic processes strongly influence short-term HIV nef quasispecies evolution in vivo.

The Antennapedia-type homeobox genes have evolved from three precursors separated early in metazoan evolution.

The developmental control genes containing an Antennapedia-type homeobox are clustered in insects and vertebrates. The evolution of these genes was studied by the construction of evolutionary trees and by statistical geometry in sequence space. The comparative analysis of the homeobox sequences reveals the subdivision of the Antennapedia-type homeobox genes into three classes early in metazoan evolution. This observation suggests an important function of these genes even in the most primitive metazoans. Subsequent duplication events generated a cluster of at least five homeobox genes in the last common ancestor of insects and vertebrates. These genes later independently gave rise to the 13 groups of paralogous genes in vertebrates and to the 11 Antennapedia-type genes in the Drosophila complexes.

Analysis of the envelope region of the highly divergent HIV-2ALT isolate extends the known range of variability within the primate immunodeficiency viruses.

HIV-2ALT is a highly divergent HIV-2-related isolate that is genetically equidistant to the prototypic HIV-2 strains, defined by HIV-2ROD, and to the simian immunodeficiency viruses SIVmac and SIVsm. We have now cloned and sequenced the envelope region of HIV-2ALT, thus completing the analysis of the whole viral genome. The sequences of env and nef and of the second exons of tat and rev were compared with those of the other viruses of the HIV-2/SIVsm/SIVmac group. Despite of the high degree of variation of HIV-2ALT, functional domains of the genes are conserved. Although in env, the overall pattern of constant and variable domains is maintained, many single amino acid exchanges exist at positions previously thought to be constant in HIV-2 strains. In addition, when compared with a broader spectrum of immunodeficiency viruses, which includes SIVMND from mandrill and SIVAGM from African green monkey, HIV-2ALT Env has a high percentage of amino acid exchanges, which are unique to this strain. This underlines the separate branch of HIV-2ALT within the phylogenetic tree and makes obvious the inclusion of such divergent strains in preventive and therapeutic programs.