Biomedical subjects

Michel C Milinkovitch

Publications and source records attributed to Michel C Milinkovitch.

17 recordsLinked to original sources

PubMed2006

A non-linear optimization procedure to estimate distances and instantaneous substitution rate matrices under the GTR model.

MOTIVATION: The general-time-reversible (GTR) model is one of the most popular models of nucleotide substitution because it constitutes a good trade-off between mathematical tractability and biological reality. However, when it is applied for inferring evolutionary distances and/or instantaneous rate matrices, the GTR model seems more prone to inapplicability than more restrictive time-reversible models. Although it has been previously noted that the causes for intractability are caused by the impossibility of computing the logarithm of a matrix characterised by negative eigenvalues, the issue has not been investigated further. RESULTS: Here, we formally characterize the mathematical conditions, and discuss their biological interpretation, which lead to the inapplicability of the GTR model. We investigate the relations between, on one hand, the occurrence of negative eigenvalues and, on the other hand, both sequence length and sequence divergence. We then propose a possible re-formulation of previous procedures in terms of a non-linear optimization problem. We analytically investigate the effect of our approach on the estimated evolutionary distances and transition probability matrix. Finally, we provide an analysis on the goodness of the solution we propose. A numerical example is discussed.

Algorithms↗

PubMed2006

Molecular phylogenetic analyses indicate multiple independent emergences of parasitism in Myzostomida (Protostomia).

The fossil record indicates that Myzostomida, an enigmatic group of marine worms, traditionally considered as annelids, have exhibited a symbiotic relationship with echinoderms, especially crinoids, for nearly 350 million years. All known extant myzostomids are associated with echinoderms and infest their integument, gonads, celom, or digestive system. Using nuclear (18S rDNA) and mitochondrial (16S and COI) DNA sequence data from 37 myzostomid species representing nine genera, we report here the first molecular phylogeny of the Myzostomida and investigate the evolution of their various symbiotic associations. Our analyses indicate that the two orders Proboscidea and Pharyngidea do not constitute natural groupings. Character reconstruction analyses strongly suggest that (1) the ancestor of all extant myzostomids was an ectocommensal that first infested crinoids, and then asteroids and ophiuroids, and (2) parasitism in myzostomids emerged multiple times independently.

Animals↗

PubMed2006

Phylogeny and biogeography of a cosmopolitan frog radiation: Late cretaceous diversification resulted in continent-scale endemism in the family ranidae.

Ranidae is a large anuran group with a nearly cosmopolitan distribution. We investigated the phylogenetic relationships and early biogeographic history of ranid frogs, using 104 representatives of all subfamilies and families, sampled from throughout their distribution. Analyses of approximately 1570 bp of nuclear gene fragments (Rag-1, rhod, Tyr) and approximately 2100 bp of the mitochondrial genome (12S rRNA, tRNAVAL, 16S rRNA) indicate that the monophyly of several taxa can be rejected with high confidence. Our tree is characterized by a clear historical association of each major clade with one Gondwanan plate. This prevalence of continent-scale endemism suggests that plate tectonics has played a major role in the distribution of ranid frogs. We performed dispersal-vicariance analyses, as well as analyses constrained by paleogeographic data, to estimate ancestral distributions during early ranid diversification. Additionally, we used molecular clock analyses to evaluate whether these scenarios fit the temporal framework of continental breakup. Our analyses suggest that a scenario in which the ancestors of several clades (Rhacophorinae, Dicroglossinae, Raninae) reached Eurasia via the Indian subcontinent, and the ancestor of Ceratobatrachinae entered via the Australia-New Guinea plate, best fits the paleogeographic models and requires the fewest number of dispersal/vicariance events. However, several alternatives, in which part of the ranid fauna colonized Laurasia from Africa, are not significantly worse. Most importantly, all hypotheses make clear predictions as to where to expect key fossils and where to sample other living ranids, and thus constitute a strong basis for further research.

Animals↗

PubMed2005

OligoFaktory: a visual tool for interactive oligonucleotide design.

SUMMARY: The OligoFaktory is a set of tools for the design, on an arbitrary number of target sequences, of high-quality long oligonucleotide for micro-array, of primer pair for PCR, of siRNA and more. The user-centered interface exists in two flavours: a web portal and a standalone software for Mac OS X Tiger. A unified presentation of results provides overviews with distribution charts and relative location bar graphs, as well as detailed features for each oligonucleotide. Input and output files conform to a common XML interchange file format to allow both automatic generation of input data, archiving, and post-processing of results. The design pipeline can use BLAST servers to evaluate specificity of selected oligonucleotides. AVAILABILITY: The web portal http://ueg.ulb.ac.be/oligofaktory/; the software for Macintosh: http://www.oligofaktory.org/

Algorithms↗

PubMed2005

Evaluating intraspecific "network" construction methods using simulated sequence data: do existing algorithms outperform the global maximum parsimony approach?

In intraspecific studies, reticulated graphs are valuable tools for visualization, within a single figure, of alternative genealogical pathways among haplotypes. As available software packages implementing the global maximum parsimony (MP) approach only give the possibility to merge resulting topologies into less-resolved consensus trees, MP has often been neglected as an alternative approach to purely algorithmic (i.e., methods defined solely on the basis of an algorithm) "network" construction methods. Here, we propose to search tree space using the MP criterion and present a new algorithm for uniting all equally most parsimonious trees into a single (possibly reticulated) graph. Using simulated sequence data, we compare our method with three purely algorithmic and widely used graph construction approaches (minimum-spanning network, statistical parsimony, and median-joining network). We demonstrate that the combination of MP trees into a single graph provides a good estimate of the true genealogy. Moreover, our analyses indicate that, when internal node haplotypes are not sampled, the median-joining and MP methods provide the best estimate of the true genealogy whereas the minimum-spanning algorithm shows very poor performances.

Algorithms↗

PubMed2005

Evidence for male dispersal along the coasts but no migration in pelagic waters in dusky dolphins (Lagenorhynchus obscurus).

Using nine nuclear species-specific microsatellite loci and two mitochondrial gene fragments (cytochrome b and control region), we investigated the processes that have shaped the geographical distribution of genetic diversity exhibited by contemporary dusky dolphin (Lagenorhynchus obscurus) populations. A total of 221 individuals from four locations (Peru, Argentina, southern Africa, and New Zealand) were assayed, covering most of the species' distribution range. Although our analyses identify a general demographic decline in the Peruvian dusky dolphin stock (recently affected by high natural and human-induced mortality levels), comparison between the different molecular markers hint at an ancient bottleneck that predates recent El Niño oscillations and human exploitation. Moreover, we find evidence of a difference in dispersal behaviour of dusky dolphins along the South American coast and across the Atlantic. While data in Peruvian and Argentine waters are best explained by male-specific gene flow between these two populations, our analyses suggest that dusky dolphins from Argentina and southern Africa recently separated from an ancestral Atlantic population and, since then, diverged without considerable gene flow. The inclusion of a few New Zealand samples further confirms the low levels of genetic differentiation among most dusky dolphin populations. Only the Peruvian dusky dolphin stock is highly differentiated, especially at mitochondrial loci, suggesting that major fluctuations in its population size have led to an increased rate of genetic drift.

Africa, Southern↗

PubMed2005

Inferring contemporary levels of gene flow and demographic history in a local population of the leaf beetle Gonioctena olivacea from mitochondrial DNA sequence variation.

We have studied mitochondrial DNA variation in a local population of the leaf beetle species Gonioctena olivacea, to check whether its apparent low dispersal behaviour affects its pattern of genetic variation at a small geographical scale. We have sampled 10 populations of G. olivacea within a rectangle of 5 x 2 km in the Belgian Ardennes, as well as five populations located approximately along a straight line of 30 km and separated by distances of 3-12 km. For each sampled individual (8-19 per population), a fragment of the mtDNA control region was polymerase chain reaction-amplified and sequenced. Sequence data were analysed to test whether significant genetic differentiation could be detected among populations separated by such relatively short distances. The reconstructed genealogy of the mitochondrial haplotypes was also used to investigate the demographic history of these populations. Computer simulations of the evolution of populations were conducted to assess the minimum amount of gene flow that is necessary to explain the observed pattern of variation in the samples. Results show that migration among populations included in the rectangle of 5 x 2 km is substantial, and probably involves the occurrence of dispersal flights. This appears difficult to reconcile with the results of a previous ecological field study that concluded that most of this species dispersal occurs by walking. While sufficient migration to homogenize genetic diversity occurs among populations separated by distances of a few hundred metres to a few kilometres, distances greater than 5 km results in contrast in strong differentiation among populations, suggesting that migration is drastically reduced on such distances. Finally, the results of coalescent simulations suggest that the star-like genealogy inferred from the mtDNA sequence data is fully compatible with a past demographic expansion. However, a metapopulation structure alone (without the need to invoke a population expansion event) cannot be dismissed as the cause of this star shape.

Analysis of Variance↗

PubMed2005

Separate-component-stabilization system for protein and DNA production without the use of antibiotics.

Plasmid instability is a significant concern in the industrial utilization of microorganisms for protein or DNA production. Here we report on the development of a new and highly effective stabilization system based on the use of the ccd antidote/poison genes. For the first time, we separated the antidote gene from the poison gene: localizing the former in the plasmid and integrating the latter in the bacterial chromosome. We show that this separate-component-stabilization (SCS) strategy: (i) allows for perfect stabilization without the use of antibiotics; (ii) increases three to five times the recombinant protein production levels; and (iii) does not require any specific modification of the protein production process or culture medium. We illustrate that point by using the classical T7 promotor (i.e., used in most expression systems). Finally, we demonstrate that the SCS system increases by five the yield in DNA production, a result especially important for the design and production of gene therapy constructs void of any antibiotic resistance gene.

Anti-Bacterial Agents↗

PubMed2004

Local endemism within the Western Ghats-sri Lanka biodiversity hotspot.

The apparent biotic affinities between the mainland and the island in the Western Ghats-Sri Lanka biodiversity hotspot have been interpreted as the result of frequent migrations during recent periods of low sea level. We show, using molecular phylogenies of two invertebrate and four vertebrate groups, that biotic interchange between these areas has been much more limited than hitherto assumed. Despite several extended periods of land connection during the past 500,000 years, Sri Lanka has maintained a fauna that is largely distinct from that of the Indian mainland. Future conservation programs for the subcontinent should take into account such patterns of local endemism at the finest scale at which they may occur.

Amphibians↗

PubMed2004

Genetic analysis of a successful repatriation programme: giant Galápagos tortoises.

As natural populations of endangered species dwindle to precarious levels, remaining members are sometimes brought into captivity, allowed to breed and their offspring returned to the natural habitat. One goal of such repatriation programmes is to retain as much of the genetic variation of the species as possible. A taxon of giant Galápagos tortoises on the island of Española has been the subject of a captive breeding-repatriation programme for 33 years. Core breeders, consisting of 12 females and three males, have produced more than 1200 offspring that have been released on Española where in situ reproduction has recently been observed. Using microsatellite DNA markers, we have determined the maternity and paternity of 132 repatriated offspring. Contributions of the breeders are highly skewed. This has led to a further loss of genetic variation that is detrimental to the long-term survival of the population. Modifications to the breeding programme could alleviate this problem.

Alleles↗

PubMed2004

Molecular phylogenetic analyses indicate a wide and ancient radiation of African hepatitis delta virus, suggesting a deltavirus genus of at least seven major clades.

Hepatitis D virus (HDV) is a satellite of hepatitis B virus (HBV) for transmission and propagation and infects nearly 20 million people worldwide. The HDV genome is a compact circular single-stranded RNA genome with extensive intramolecular complementarity. Despite its different epidemiological and pathological patterns, the variability and geographical distribution of HDV are limited to three genotypes and two subtypes that have been characterized to date. Phylogenetic reconstructions based on the delta antigen gene and full-length genome sequence data show an extensive and probably ancient radiation of African lineages, suggesting that the genetic variability of HDV is much more complex than was previously thought, with evidence of additional clades. These results relate the geographic distribution of HDV more closely to the genetic variability of its helper HBV.

Adolescent↗

PubMed2003

A hidden Markov model for progressive multiple alignment.

MOTIVATION: Progressive algorithms are widely used heuristics for the production of alignments among multiple nucleic-acid or protein sequences. Probabilistic approaches providing measures of global and/or local reliability of individual solutions would constitute valuable developments. RESULTS: We present here a new method for multiple sequence alignment that combines an HMM approach, a progressive alignment algorithm, and a probabilistic evolution model describing the character substitution process. Our method works by iterating pairwise alignments according to a guide tree and defining each ancestral sequence from the pairwise alignment of its child nodes, thus, progressively constructing a multiple alignment. Our method allows for the computation of each column minimum posterior probability and we show that this value correlates with the correctness of the result, hence, providing an efficient mean by which unreliably aligned columns can be filtered out from a multiple alignment.

Algorithms↗

PubMed2003

Structure and evolution of the mitochondrial control region of leaf beetles (Coleoptera: Chrysomelidae): a hierarchical analysis of nucleotide sequence variation.

To assess the levels of variation at different evolutionary scales in the mitochondrial (mt) control region of leaf beetles, we sequenced and compared the full mt control region in two genera ( Chrysomela and Gonioctena), in two species within a genus ( Gonioctena olivacea and G. pallida), in individuals from distant populations of these species in Europe, and in individuals from populations separated by moderate (10- to 100-km) to short (<5-km) distances. In all individuals, a highly repetitive section consisting of the tandem repetition of 12 to 17 imperfect copies of a 107- to 159-bp-long core sequence was observed. This repetitive fragment accounts for roughly 50% of the full control-region length. The sequence variability among repeated elements within the control region of a given individual depends on the species considered: the variability within any G. olivacea individual is much higher than that within G. pallida individuals. Comparisons of the repeated elements, in a phylogenetic framework, within and among individuals of G. olivacea and G. pallida suggests that the repetitive section of the control region experienced recurrent duplications/deletions, leading to some degree of concerted evolution. Comparisons between Chrysomela and Gonioctena control regions revealed virtually no significant sequence similarity, except for two long stretches of A's and several [T(T)A(A)] repeats, all found in the control region of other insect orders. Our analyses allowed us to identify portions of the control region with enough variation for population genetic or phylogeographic studies.

Animals↗

PubMed2002

The metapopulation genetic algorithm: An efficient solution for the problem of large phylogeny estimation.

Large phylogeny estimation is a combinatorial optimization problem that no future computer will ever be able to solve exactly in practical computing time. The difficulty of the problem is amplified by the need to use complex evolutionary models and large taxon samplings. Hence, many heuristic approaches have been developed, with varying degrees of success. Here, we report on a heuristic approach, the metapopulation genetic algorithm, involving several populations of trees that are forced to cooperate in the search for the optimal tree. Within each population, trees are subjected to evaluation, selection, and mutation events, which are directed by using inter-population consensus information. The method proves to be both very accurate and vastly faster than existing heuristics, such that data sets comprised of hundreds of taxa can be analyzed in practical computing times under complex models of maximum-likelihood evolution. Branch support values produced by the metapopulation genetic algorithm might closely approximate the posterior probabilities of the corresponding branches.

Algorithms↗

PubMed2002

Dual chemical sequestration: a key mechanism in transitions among ecological specialization.

Platyphora leaf beetles form a vast group of tropical species each feeding on a restricted set of host plants and exhibiting bright coloration warning predators against their chemical protection. These beetles offer an exceptional opportunity for understanding the evolution of phytochemical sequestration. Indeed, qualitative studies of defensive secretions indicate that Platyphora species acquire toxicity via sequestration of plant secondary metabolites. All produce pentacyclic triterpene saponins from sequestered plant amyrins, but our analyses also indicate that many Platyphora species produce a dual chemical defence, that is, they are additionally protected by lycopsamine-type pyrolyzidine alkaloids that they also sequester from their host. This paper reports on the evolution of chemical defence and host affiliation in Platyphora leaf beetles as reconstructed on a molecular phylogeny of mitochondrial and nuclear DNA sequences. The analyses indicate that dual sequestration could be the key mechanistic means by which transitions among ecological specializations (i.e. restricted host-plant affiliations) are made possible.

Amino Acid Sequence↗

PubMed2002

Investigation of the population genetic structure and mating system in the ant Pheidole pallidula.

The origin of eusociality in haplo-diploid organisms such as Hymenoptera has been mostly explained by kin selection. However, several studies have uncovered decreased relatedness values within colonies, resulting primarily from multiple queen matings (polyandry) and/or from the presence of more than one functional queen (polygyny). Here, we report on the use of microsatellite data for the investigation of sociogenetic parameters, such as relatedness, and levels of polygyny and polyandry, in the ant Pheidole pallidula. We demonstrate, through analysis of mother-offspring combinations and the use of direct sperm typing, that each queen is inseminated by a single male. The inbreeding coefficient within colonies and the levels of relatedness between the queens and their mate are not significantly different from zero, indicating that matings occur between unrelated individuals. Analyses of worker genotypes demonstrate that 38% of the colonies are polygynous with 2-4 functional queens, and suggest the existence of reproductive skew, i.e. unequal respective contribution of queens to reproduction. Finally, our analyses indicate that colonies are genetically differentiated and form a population exhibiting significant isolation-by-distance, suggesting that some colonies originate through budding.

Animals↗

PubMed2002

Microsatellite analysis of genetic divergence among populations of giant Galápagos tortoises.

Giant Galápagos tortoises represent an interesting model for the study of patterns of genetic divergence and adaptive differentiation related to island colonization events. Recent mitochondrial DNA work elucidated the evolutionary history of the species and helped to clarify aspects of nomenclature. We used 10 microsatellite loci to assess levels of genetic divergence among and within island populations. In particular, we described the genetic structure of tortoises on the island of Isabela, where discrimination of different taxa is still subject of debate. Individual island populations were all genetically distinct. The island of Santa Cruz harboured two distinct populations. On Isabela, populations of Volcan Wolf, Darwin and Alcedo were significantly different from each other. On the other hand, Volcan Wolf showed allelic similarity with the island of Santiago. On Southern Isabela, lower genetic divergence was found between Northeast Sierra Negra and Volcan Alcedo, while patterns of gene flow were recorded among tortoises of Cerro Azul and Southeast Sierra Negra. These tortoises have endured heavy exploitation during the last three centuries and recently attracted much concern due to the current number of stochastic and deterministic threats to extant populations. Our study complements previous investigation based on mtDNA diversity and provides further information that may help devising tortoise management plans.

Animals↗