Biomedical subjects

Marcos Pérez-Losada

Publications and source records attributed to Marcos Pérez-Losada.

12 recordsLinked to original sources

PubMed2006

Temporal trends in gonococcal population genetics in a high prevalence urban community.

Molecular evolutionary studies can provide insights into the spread of infectious diseases and inform infection control measures. We performed a population genetic analysis of gonococcal isolates obtained over a 15-year interval in Baltimore, MD, where gonorrhea is highly prevalent. Categorical analysis of genetic differentiation revealed temporal structuring of the gonococcal population. The use of a new method to determine the historical demography of Neisseria gonorrhoeae from sequence data showed a strong correlation with trends in the number of reported cases of N. gonorrhoeae. The historical trends may also reflect the influence of social and demographic factors and the impact of antimicrobial resistance on the molecular epidemiology of gonorrhea in Baltimore over the past 2 decades. The strong correlation between the population genetic inferences over the last 20 years and the demographic data collected over the same time period demonstrates the utility of these approaches for the accurate inference of complex population dynamics using multilocus sequence data. The real time application of population genetic analysis can provide sentinel data on gonococcal prevalence, antibiotic resistance patterns and changing epidemiology of gonococcal infections.

Adult↗

PubMed2006

New methods for inferring population dynamics from microbial sequences.

The reduced cost of high throughput sequencing, increasing automation, and the amenability of sequence data for evolutionary analysis are making DNA data (or the corresponding amino acid sequences) the molecular marker of choice for studying microbial population genetics and phylogenetics. Concomitantly, due to the ever-increasing computational power, new, more accurate (and sometimes faster), sequence-based analytical approaches are being developed and applied to these new data. Here we review some commonly used, recently improved, and newly developed methodologies for inferring population dynamics and evolutionary relationships using nucleotide and amino acid sequence data, including: alignment, model selection, bifurcating and network phylogenetic approaches, and methods for estimating demographic history, population structure, and population parameters (recombination, genetic diversity, growth, and natural selection). Because of the extensive literature published on these topics this review cannot be comprehensive in its scope. Instead, for all the methods discussed we introduce the approaches we think are particularly useful for analyses of microbial sequences and where possible, include references to recent and more inclusive reviews.

Bacteria↗

PubMed2006

Evolution of Afrotropical freshwater crab lineages obscured by morphological convergence.

We use sequence data derived from six DNA gene loci to examine evolutionary and biogeographic affinities among all freshwater crab families. With an emphasis on the Afrotropical fauna that includes Africa, Madagascar, and the Seychelles, we test the proposed Gondwanan cladogenesis of the group. Phylogenetic results demonstrate that contemporary distribution patterns of freshwater crab lineages are incongruent with the expected area cladogram of continental fragmentation. Instead, our phylogenetic estimate and divergence time estimation indicate a post-Gondwanan, early Cretaceous cladogenesis for freshwater crabs implying that the acquisition of a freshwater lifestyle was achieved more recently. A dispersal hypothesis as opposed to vicariance appears to best explain the contemporary distribution pattern of this group. However, our results do not explicitly disprove a Gondwanan origin for the Afrotropical freshwater crabs. Alarmingly, these results suggest that most of the currently recognized freshwater crab families are unreliable taxonomic groupings since virtually no Afrotropical freshwater crab families formed monophyletic units thus obscuring inferred biogeographic relationships. Convergence in characters associated with the terminal segment of the mandibular palp is clearly a pervasive obstacle in the taxonomy of this group.

Animals↗

PubMed2006

Phylogenomics and molecular evolution of polyomaviruses.

We provide in this chapter an overview of the basic steps to reconstruct evolutionary relationships through standard phylogeny estimation approaches as well as network approaches for sequences more closely related. We discuss the importance of sequence alignment, selecting models of evolution, and confidence assessment in phylogenetic inference. We also introduce the reader to a variety of software packages used for such studies. Finally, we demonstrate these approaches throughout using a data set of 33 whole genomes of polyomaviruses. A robust phylogeny of these genomes is estimated and phylogenetic relationships among the polyomaviruses determined using Bayesian and maximum likelihood approaches. Furthermore, population samples of SV40 are used to demonstrate the utility of network approaches for closely related sequences. The phylogenetic analysis suggested a close relationship among the BK viruses, JC viruses, and SV40 with a more distant association with mouse polyomavirus, monkey polymavirus (LPV) and then avian polyomavirus (BFDV).

Computational Biology↗

PubMed2006

Longitudinal population analysis of dual infection with recombination in two strains of HIV type 1 subtype B in an individual from a Phase 3 HIV vaccine efficacy trial.

This study documents a case of coinfection (simultaneous infection of an individual with two or more strains) of two HIV-1 subtype B strains in an individual from a Phase 3 HIV-1 vaccine efficacy trial, conducted in North American and the Netherlands. We examined 86 full-length gp120 (env) gene sequences from this individual collected from nine different time points over a 20-month period. We estimated evolutionary relationships using maximum likelihood and Bayesian methods and inferred recombination breakpoints and recombinant sequences using phylogenetic and substitutional methods. These analyses identified two strongly supported monophyletic clades (clades A and B) of 14 and 69 sequences each and a small paraphyletic recombinant clade of three sequences. We then studied the genetic characteristics of these lineages by comparing estimates of genetic diversity generated by mutation and recombination and adaptive selection within a coalescent and maximum likelihood framework. Our results suggest significant differences on the evolutionary dynamics of these strains. We then discuss the implications of these results for vaccine development.

AIDS Vaccines↗

PubMed2006

Comparing phylogenetic codivergence between polyomaviruses and their hosts.

Seventy-two full genomes corresponding to nine mammalian (67 strains) and two avian (5 strains) polyomavirus species were analyzed using maximum likelihood and Bayesian methods of phylogenetic inference. Our fully resolved and well-supported (bootstrap proportions > 90%; posterior probabilities = 1.0) trees separate the bird polyomaviruses (avian polyomavirus and goose hemorrhagic polyomavirus) from the mammalian polyomaviruses, which supports the idea of spitting the genus into two subgenera. Such a split is also consistent with the different viral life strategies of each group. Simian (simian virus 40, simian agent 12 [Sa12], and lymphotropic polyomavirus) and rodent (hamster polyomavirus, mouse polyomavirus, and murine pneumotropic polyomavirus [MPtV]) polyomaviruses did not form monophyletic groups. Using our best hypothesis of polyomavirus evolutionary relationships and established host phylogenies, we performed a cophylogenetic reconciliation analysis of codivergence. Our analyses generated six optimal cophylogenetic scenarios of coevolution, including 12 codivergence events (P < 0.01), suggesting that Polyomaviridae coevolved with their avian and mammal hosts. As individual lineages, our analyses showed evidence of host switching in four terminal branches leading to MPtV, bovine polyomavirus, Sa12, and BK virus, suggesting a combination of vertical and horizontal transfer in the evolutionary history of the polyomaviruses.

Animals↗

PubMed2005

Model-based multi-locus estimation of decapod phylogeny and divergence times.

Phylogenetic relationships among all of the major decapod infraorders have never been estimated using molecular data, while morphological studies produce conflicting results. In the present study, the phylogenetic relationships among the decapod basal suborder Dendrobranchiata and all of the currently recognized decapod infraorders within the suborder Pleocyemata (Caridea, Stenopodidea, Achelata, Astacidea, Thalassinidea, Anomala, and Brachyura) were inferred using 16S mtDNA, 18S and 28S rRNA, and the histone H3 gene. Phylogenies were reconstructed using the model-based methods of maximum likelihood and Bayesian methods coupled with Markov Chain Monte Carlo inference. The phylogenies revealed that the seven infraorders are monophyletic, with high clade support values (bp>70; pP>0.95) under both methods. The two suborders also were recovered as monophyletic, but with weaker support (bp=70; pP=0.74). Although the nodal support values for infraordinal relationships were low (bp<50; pP<0.77) the Anomala and Brachyura were basal to the rest of the 'Reptantia' in both reconstructions and using Bayesian tree topology tests alternate morphology-based hypotheses were rejected (P<0.01). Newly developed multi-locus Bayesian and likelihood heuristic rate-smoothing methods to estimate divergence times were compared using eight fossil and geological calibrations. Estimated times revealed that the Decapoda originated earlier than 437MYA and that the radiation within the group occurred rapidly, with all of the major lineages present by 325MYA. Node time estimation under both approaches is severely affected by the number and phylogenetic distribution of the fossil calibrations chosen. For analyses incorporating fossils as fixed ages, more consistent results were obtained by using both shallow and deep or clade-related calibration points. Divergence time estimation using fossils as lower and upper limits performed well with as few as one upper limit and a single deep fossil lower limit calibration.

Animals↗

PubMed2005

Population genetics of Neisseria gonorrhoeae in a high-prevalence community using a hypervariable outer membrane porB and 13 slowly evolving housekeeping genes.

Baltimore, Md., is an urban community with a high prevalence of Neisseria gonorrhoeae. Due to partially protective immune responses, introduction of new strains from other host populations, and exposure of N. gonorrhoeae to antibiotics, the phenotypic and genotypic characteristics of the circulating strains can fluctuate over time. Understanding the overall genetic diversity and population structure of N. gonorrhoeae is essential for informing public health interventions to eliminate this pathogen. We studied gonococci population genetics in Baltimore by analyzing a hypervariable and strongly selected outer membrane porB gene and 13 slowly evolving and presumably neutral housekeeping genes (abcZ, adk, aroE, fumC, gdh, glnA, gnd, pdhC, pgm, pilA, ppk, pyrD, and serC) in 204 isolates collected in 1991, 1996, and 2001 from male and female patients of two public sexually transmitted diseases clinics. Genetic diversity (), recombination (C), growth (g), population structure, and adaptive selection under codon-substitution and amino acid property models were estimated and compared between these two gene classes. Estimates of the F(ST) fixation index and the chi(2) test of sequence absolute frequencies revealed significant temporal substructuring for both gene types. Baltimore's N. gonorrhoeae populations have increased since 1991 as indicated by consistent positive values of g. Female patients showed similar or lower levels of and C than male patients. Within the MLST housekeeping genes, levels of and C ranged from 0.001-0.013 and 0.000-0.018, respectively. Overall recombination seems to be the dominant force driving evolution in these populations. All loci showed amino acid sites and physicochemical properties under adaptive (or positive-destabilizing) selection, rejecting the generally assumed hypothesis of stabilizing selection for these MLST genes. Within the porB gene, protein I B showed higher and C values than protein I A. Directional positive selection possibly mediated by the immune system operates to a significant extent in the protein I sequences, as indicated by the distribution of the positively selected sites in the surface-exposed loops. Thirteen amino acid physicochemical properties seem to drive protein evolution of the PI porins in N. gonorrhoeae.

Amino Acid Sequence↗

PubMed2005

Population genetics of microbial pathogens estimated from multilocus sequence typing (MLST) data.

The inference of population recombination (rho), population mutation (Theta), and adaptive selection is of great interest in microbial population genetics. These parameters can be efficiently estimated using explicit statistical frameworks (evolutionary models) that describe their effect on gene sequences. Within this framework, we estimated rho and Theta using a coalescent approach, and adaptive (or destabilizing) selection under heterogeneous codon-based and amino acid property models in microbial sequences from MLST databases. We analyzed a total of 91 different housekeeping gene regions (loci) corresponding to one fungal and sixteen bacterial pathogens. Our results show that these three population parameters vary extensively across species and loci, but they do not seem to be correlated. For the most part, estimated recombination rates among species agree well with previous studies. Over all taxa, the rho/Theta ratio suggests that each factor contributes similarly to the emergence of variant alleles. Comparisons of Theta estimated under finite- and infinite-site models indicate that recurrent mutation (i.e., multiple mutations at some sites) can increase Theta by up to 39%. Significant evidence of molecular adaptation was detected in 28 loci from 13 pathogens. Three of these loci showed concordant patterns of adaptive selection in two to four different species.

Alleles↗

PubMed2005

Phylogeny and biogeography of the freshwater crayfish Euastacus (Decapoda: Parastacidae) based on nuclear and mitochondrial DNA.

Euastacus crayfish are endemic to freshwater ecosystems of the eastern coast of Australia. While recent evolutionary studies have focused on a few of these species, here we provide a comprehensive phylogenetic estimate of relationships among the species within the genus. We sequenced three mitochondrial gene regions (COI, 16S, and 12S) and one nuclear region (28S) from 40 species of the genus Euastacus, as well as one undescribed species. Using these data, we estimated the phylogenetic relationships within the genus using maximum-likelihood, parsimony, and Bayesian Markov Chain Monte Carlo analyses. Using Bayes factors to test different model hypotheses, we found that the best phylogeny supports monophyletic groupings of all but two recognized species and suggests a widespread ancestor that diverged by vicariance. We also show that Euastacus and Astacopsis are most likely monophyletic sister genera. We use the resulting phylogeny as a framework to test biogeographic hypotheses relating to the diversification of the genus.

Animals↗

PubMed2004

Unraveling the evolutionary radiation of the thoracican barnacles using molecular and morphological evidence: a comparison of several divergence time estimation approaches.

The Thoracica includes the ordinary barnacles found along the sea shore and is the most diverse and well-studied superorder of Cirripedia. However, although the literature abounds with scenarios explaining the evolution of these barnacles, very few studies have attempted to test these hypotheses in a phylogenetic context. The few attempts at phylogenetic analyses have suffered from a lack of phylogenetic signal and small numbers of taxa. We collected DNA sequences from the nuclear 18S, 28S, and histone H3 genes and the mitochondrial 12S and 16S genes (4,871 bp total) and data for 37 adult and 53 larval morphological characters from 43 taxa representing all the extant thoracican suborders (except the monospecific Brachylepadomorpha). Four Rhizocephala (highly modified parasitic barnacles) taxa and a Rhizocephala + Acrothoracica (burrowing barnacles) hypothetical ancestor were used as the outgroup for the molecular and morphological analyses, respectively. We analyzed these data separately and combined using maximum likelihood (ML) under "hill-climbing" and genetic algorithm heuristic searches, maximum parsimony procedures, and Bayesian inference coupled with Markov chain Monte Carlo techniques under mixed and homogeneous models of nucleotide substitution. The resulting phylogenetic trees answered key questions in barnacle evolution. The four-plated Iblomorpha were shown as the most primitive thoracican, and the plateless Heteralepadomorpha were placed as the sister group of the Lepadomorpha. These relationships suggest for the first time in an invertebrate that exoskeleton biomineralization may have evolved from phosphatic to calcitic. Sessilia (nonpedunculate) barnacles were depicted as monophyletic and appear to have evolved from a stalked (pedunculate) multiplated (5+) scalpelloidlike ancestor rather than a five-plated lepadomorphan ancestor. The Balanomorpha (symmetric sessile barnacles) appear to have the following relationship: (Chthamaloidea(Coronuloidea(Tetraclitoidea, Balanoidea))). Thoracican divergence times were estimated under ML-based local clock, Bayesian, and penalized likelihood approaches using an 18S data set and three calibration points: Heteralepadomorpha = 530 million years ago (MYA), Scalpellomorpha = 340 MYA, and Verrucomorpha = 120 MYA. Estimated dates varied considerably within and between approaches depending on the calibration point. Highly parameterized local clock models that assume independent rates (r > or = 15) for confamilial or congeneric species generated the most congruent estimates among calibrations and agreed more closely with the barnacle fossil record. Reasonable estimates were also obtained under the Bayesian procedure of Kishino et al. (2001, Mol. Biol. Evol. 18:352-361) but using multiple calibrations. Most of the dates estimated under the Bayesian procedure of Aris-Brosou and Yang (2002, Syst. Biol. 51:703-714) and the penalized likelihood method using single and/or multiple calibrations were inconsistent among calibrations and did not fit the fossil record.

Animals↗

PubMed2004

Molecular systematics and biogeography of the southern South american freshwater "crabs" Aegla (decapoda: Anomura: Aeglidae) using multiple heuristic tree search approaches.

Recently new heuristic genetic algorithms such as Treefinder and MetaGA have been developed to search for optimal trees in a maximum likelihood (ML) framework. In this study we combined these methods with other standard heuristic approaches such as ML and maximum parsimony hill-climbing searches and Bayesian inference coupled with Markov chain Monte Carlo techniques under homogeneous and mixed models of evolution to conduct an extensive phylogenetic analysis of the most abundant and widely distributed southern South American freshwater"crab,"the Aegla(Anomura: Aeglidae). A total of 167 samples representing 64 Aegla species and subspecies were sequenced for one nuclear (28S rDNA) and four mitochondrial (12S and 16S rDNA, COI, and COII) genes (5352 bp total). Additionally, six other anomuran species from the genera Munida,Pachycheles, and Uroptychus(Galatheoidea), Lithodes(Paguroidea), and Lomis(Lomisoidea) and the nuclear 18S rDNA gene (1964 bp) were included in preliminary analyses for rooting the Aegla tree. Nonsignificantly different phylogenetic hypotheses resulted from all the different heuristic methods used here, although the best scored topologies found under the ML hill-climbing, Bayesian, and MetaGA approaches showed considerably better likelihood scores (Delta> 54) than those found under the MP and Treefinder approaches. Our trees provided strong support for most of the recognized Aegla species except for A. cholchol,A. jarai,A. parana,A. marginata, A. platensis, and A. franciscana, which may actually represent multiple species. Geographically, the Aegla group was divided into a basal western clade (21 species and subspecies) composed of two subclades with overlapping distributions, and a more recent central-eastern clade (43 species) composed of three subclades with fairly well-recognized distributions. This result supports the Pacific-Origin Hypothesis postulated for the group; alternative hypotheses of Atlantic or multiple origins were significantly rejected by our analyses. Finally, we combined our phylogenetic results with previous hypotheses of South American paleodrainages since the Jurassic to propose a biogeographical framework of the Aegla radiation.

Animals↗