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PubMed2002

Evolution of the PP2C family in Caenorhabditis: rapid divergence of the sex-determining protein FEM-2.

To investigate the causes and functional significance of rapid sex-determining protein evolution we compared three Caenorhabditis elegans genes encoding members of the protein phosphatase 2C (PP2C) family with their orthologs from another Caenorhabditis species (strain CB5161). One of the genes encodes FEM-2, a sex-determining protein, while the others have no known sex-determining role. FEM-2's PP2C domain was found to be more diverged than the other PP2C domains, supporting the notion that sex-determining proteins are subjected to selective pressures that allow for or cause rapid divergence. Comparison of the positions of amino acid substitutions in FEM-2 with a solved three-dimensional structure suggests that the catalytic face of the protein is highly conserved among C. elegans, CB5161, and another closely related species C. briggsae. However, the non-conserved regions of FEM-2 cannot be said to lack functional importance, since fem-2 transgenes from the other species were unable to rescue the germ-line defect caused by a C. elegans fem-2 mutation. To test whether fem-2 functions as a sex-determining gene in the other Caenorhabditis species we used RNA-mediated interference (RNAi). fem-2 (RNAi) in C. elegans and C. briggsae caused germ-line feminization, but had no noticeable effect in CB5161. Thus the function of fem-2 in CB5161 remains uncertain.

Amino Acid Sequence↗

PubMed1986

Comparative kinetics study of the evolution of freshwater aquatic toxicity and biodegradability of linear and branched alkylbenzene sulfonates.

Evolution of both primary biodegradability and acute toxicity to daphnia and zebra fish of a linear alkylbenzene sodium sulfonate (LAS) and a branched alkylbenzene sodium sulfonate (BAS) have been measured simultaneously. In six of eight experiments, LAS was biodegraded to 90% in 7 days and BAS to 70% in 7 days. In the two other experiments, both LAS and BAS have shown the same biodegradation speed and reached the same biodegradation level in 7 days: 45% in one experiment and 55% in the other. The composition of bacteria population and the level of cellular ATP of the inoculum play a decisive role in the biodegradation. These results confirm that it is essential to know the composition of bacteria population present in the inoculum as well as their biochemical characteristics to accurately interpret results of biodegradation tests. In the case of a rapid primary biodegradation of LAS and BAS, the acute toxicity of LAS remains three times as high as that of BAS for at least 24 hr toward daphnia and 48 hr toward zebra fish. Their acute toxicity to daphnia and zebra fish become equivalent only after 72 hr. When primary biodegradation of both products is slower, the acute toxicity of LAS remains higher than that of BAS for more than 7 days.

Alkanesulfonates↗

PubMed1998

Gulliver's further travels: the necessity and difficulty of a hierarchical theory of selection.

For principled and substantially philosophical reasons, based largely on his reform of natural history by inverting the Paleyan notion of overarching and purposeful beneficence in the construction of organisms, Darwin built his theory of selection at the single causal level of individual bodies engaged in unconscious (and metaphorical) struggle for their own reproductive success. But the central logic of the theory allows selection to work effectively on entities at several levels of a genealogical hierarchy, provided that they embody a set of requisite features for defining evolutionary individuality. Genes, cell lineages, demes, species, and clades-as well as Darwin's favoured organisms-embody these requisite features in enough cases to form important levels of selection in the history of life. R. A. Fisher explicitly recognized the unassailable logic of species selection, but denied that thsi real process could be important in evolution because, compared with the production of new organisms within a species, the origin of new species is so rare, and the number of species within most clades so low. I review this and other classical arguments against higher-level selection, and conclude (in the first part of this paper) that they are invalid in practice for interdemic selection, and false in principle for species selection. Punctuated equilibrium defines the individuality of species and refutes Fisher's classical argument based on cycle time. In the second part of the paper, I argue that we have failed to appreciate the range and power of selection at levels above and below the organismic because we falsely extrapolate the defining properties of organisms to these other levels (which are characterized by quite different distinctive features), and then regard the other levels as impotent because their effective individuals differ so much from organisms. We would better appreciate the power and generality of hierarchical models of selection if we grasped two key principles: first, that levels can interact in all modes (positively, negatively, and orthogonally), and not only in the negative style (with a higher level suppressing an opposing force of selection from the lower level) that, for heuristic and operational reasons, has received almost exclusive attention in the existing literature; and second, that each hierarchical level differs from all others in substantial and interesting ways, both in the style and frequency of patterns in change and causal modes.

Animals↗

PubMed2003

Study of the cardiac alterations in HIV-infected children consequent to the antiretroviral therapy. Prospective study of 47 cases.

OBJECTIVE: Detect of cardiac alterations in children with AIDS and compare their evolution with the administration of only one anti-retroviral and the recent cases who received drugs in combination. METHODS: We prospectively studied 47 children in 3 groups: group 1, 20 cases treated only with zidovudine; group 2, 10 patients treated initially with zidovudine and later with a combination of drugs and in group 3, 17 patients, who receiced two or three since the beginning. In all patients it was done chest X-ray, EKG and echocardiography every 6 months and after death complete pathological study. RESULTS: Among the 45 patients cases 26 (57%) were index cases. Malnutrition, diarrhea tachycardia, signs of congestive heart failure, pericardial effusion, abnormal ventricular repolarization and arrhythmias were more frequent in group 1. Echocardiographic abnormalities were present in 10 (50%) children of group 1. They were less frequent in the others two groups. In regard to the outcome in group 1, two patients had worsening of sings of cardiomyopaty and 4 died. Cardiac dysfunction in all cases of group 2 and 3 improved with the medication. CONCLUSION: The children who received combination and their cardiac alterations had more favorable outcome than those who received only one drug.

AIDS-Related Opportunistic Infections↗

PubMedDate not supplied

[Is physical training useful for elderly patients with ischemic heart disease?].

UNLABELLED: The aim of the paper is the study of the effects of a supervised physical training at old patients with ischaemic heart disease. METHODS: 74 patients with ischaemic left ventricular dysfunction have been followed during a supervised physical training consisting of a daily programme of exercise over a period of 21 +/- 10 days. They were parted in Group A (n = 26) over 60 years old and Group B (n = 48) under this age. The heart rate (HR), systolic and diastolic heart pressure (SHP respectively DHP), the time-tension index (TTI) were registered during the rest, the peak intensity of exercise and the recovery. These parameters were compared in evolution at each group and also between the groups. RESULTS: At Group A, at the end of the period, SHP at the peak intensity decreased (from 146 +/- 19 to 137 +/- 14 mmHg, p = 0.01), also SHP in the recovery period (from 119 +/- 10 to 116 +/- 10 mmHg, p = 0.01) and HR during the recovery time (from 77 +/- 8/min to 73 +/- 6/min, p = 0.03). The total length of the session time increased (from 12 +/- 4 min to 21 +/- 6 min, p = 0.01) and also the duration of the peak exercise time (from 3.6 +/- 1.0 min to 7.7 +/- 2.9 min, p = 0.03), in the condition of maintaining a HR at the peak exercise of about 75-76% of the maximum HR obtained at a previous exercise testing. The improvement of the training parameters was similar with Group B, except the duration of the session, longer at the last group (21 +/- 6 min at Group A vs. 25 +/- 7 min at Group B, p = 0.02) and the duration of the peak intensity (7.7 +/- 1.0 min at Group A vs. 9.1 +/- 2.9 min at Group B, p = 0.02). CONCLUSIONS: Old patients with ischaemic left ventricular dysfunction improve their exercise capacity as well as the younger ones; the benefits of a supervised physical exercise are evident regardless of age.

Adult↗

PubMed2005

Fluoroquinolones vs macrolides in the treatment of Legionnaires disease.

BACKGROUND: Erythromycin has been the treatment of choice for Legionnaires disease (LD). However, treatment failure and experimental evidence of its bacteriostatic effect have led to evaluation of new drugs such as fluoroquinolones. This study compared the evolution of patients with LD treated with macrolides and fluoroquinolones. METHODS: A prospective observational study was performed, and 130 patients from three centers were included. Diagnoses were made using Legionella urinary antigen assay in all patients. Patients receiving any antibiotic > 36 h before starting the study therapy were excluded. Group 1 included 76 patients who received macrolides (33 patients with erythromycin and 43 patients with clarithromycin), and group 2 included 54 patients treated with fluoroquinolones (50 patients with levofloxacin and 4 patients with ofloxacin). RESULTS: No significant differences were seen between the two groups regarding age, sex, smoking, alcohol intake, underlying diseases, or community/hospital acquisition. The time from onset of LD symptoms until the initiation of antibiotic treatment was 78.5 h and 92.7 h in groups 1 and 2, respectively (p = 0.1). Time to apyrexia was significantly longer in the macrolide group (77.1 h vs 48 h for groups 1 and 2, respectively; p = 0.000). There were no differences according to radiology, clinical complications, or mortality. Nevertheless, a trend to a longer hospital stay was observed in the macrolide group (9.9 days vs 7.6 days in groups 1 and 2, respectively; p = 0.09). CONCLUSIONS: Fluoroquinolones were as effective as erythromycin in the treatment of LD. It is of note that time to apyrexia was significantly shorter and hospital stay tended to be shorter in patients receiving fluoroquinolones.

Adult↗

PubMed2004

Genome evolution in yeasts.

Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates. A total of approximately 24,200 novel genes were identified, the translation products of which were classified together with Saccharomyces cerevisiae proteins into about 4,700 families, forming the basis for interspecific comparisons. Analysis of chromosome maps and genome redundancies reveal that the different yeast lineages have evolved through a marked interplay between several distinct molecular mechanisms, including tandem gene repeat formation, segmental duplication, a massive genome duplication and extensive gene loss.

Chromosomes, Fungal↗

PubMed2005

A comparison of fitting growth models with a genetic algorithm and nonlinear regression.

A genetic algorithm (GA), an optimization procedure based on the theory of evolution, was compared with nonlinear regression for the ability of the 2 algorithms to fit the coefficients of poultry growth models. It was hypothesized that the nonlinear approach of using GA to define the parameters of growth equations would better fit the growth equations than the use of nonlinear regression. Two sets of growth data from the literature, consisting of male broiler BW grown for 168 and 170 d, were used in the study. The growth data were fit to 2 forms of the logistic model, the Gompertz, the Gompertz-Laird, and the saturated kinetic models using the SAS nonlinear algorithm (NLIN) procedure and a GA. There were no statistical differences for the comparison of the residuals (the difference between observed and predicted BWs) of growth models fit by a GA or nonlinear regression. The plotted residuals for the nonlinear regression and GA-determined growth values confirmed observations of others that the residuals have oscillations resembling sine waves that are not represented by the growth models. It was found that GA could successfully determine the coefficients of growth equations. A disadvantage of slowness in converging to the solution was found for the GA. The advantage of GA over traditional nonlinear regression is that only ranges need be specified for the parameters of the growth equations, whereas estimates of the coefficients need to be determined, and in some programs the derivatives of the growth equations need to be identified. Depending on the goal of the research, solving multivariable complex functions with an algorithm that considers several solutions at the same time in an evolutionary mode can be considered an advantage especially where there is a chance for the solution to converge on a local optimum when a global optimum is desired. It was concluded that the fitting of the growth equations was not so much a problem with the fitting methodology as it is with the form of the equation.

Algorithms↗

PubMed2004

Criticality and synchrony of fluctuations in rhythmical brain activity: pretransitional effects in epileptic patients.

In extending our previous results demonstrating critical fluctuations in electropathophysiological brain activity prior to onset of partial epileptic seizures, we used once again Haken's approach to self-organized complex systems, which resorts to identifying an order parameter. A renormalized density in phase space and a renormalized differential density were defined and substituted for the Lerner density, which we used previously. Fluctuations in electropathophysiological activity, consisting of periods of high activity recorded from both depth and scalp electrodes in six presurgical patients, were characterized on different time scales. Extension in space of the fluctuations was characterized by observing their synchronous occurrence in different areas of the brain. By simultaneously establishing the fluctuations' criticality, we were observing "synchronous instabilities". Criticality followed from characterizing the time course of the synchronously arising fluctuations, when approaching seizure onset (i). by their slowing, for the longer-lasting ones (up to about 2 min), and (ii). by their increase in rate of production, for those of shorter duration (up to 20-30 s). Critical behavior may be displayed in favorable cases over more than 1 h prior to seizure onset. Other effects are also described that in some cases may interfere with the simple time course of fluctuations and must be given further consideration, particularly with a view to application to seizure anticipation. Because periods of high activity are involved, any marker of increased electropathophysiological activity in the brain may, in principle, play the role of an order parameter or of an approximate order parameter, e.g., a signal's root-mean-square amplitude, or its excess energy content. Such markers may be put to use for the fluctuations they display or merely for their average time evolution prior to seizure onset. We compared the time evolution, prior to onset, of the excess production rate of synchronies and of the signals' excess energy content, both averaged over signal sections of a chosen duration. In view of potential noninvasive applications, those scalp electrodes showing effects similar to the observations we made at the epileptogenic focus were identified, and the time course of their order parameters prior to seizure onset was analyzed.

Brain↗

PubMed2005

Hepatitis B virus-associated polyarteritis nodosa: clinical characteristics, outcome, and impact of treatment in 115 patients.

Hepatitis B virus-associated polyarteritis nodosa (HBV-PAN) is a typical form of classic PAN whose pathogenesis has been attributed to immune-complex deposition with antigen excess. We conducted the current study to 1) analyze the frequency of HBV infection in patients with PAN, in light of the classification systems described since 1990; 2) describe the clinical characteristics of HBV-PAN; 3) compare the evolution according to conventional or antiviral treatment; and 4) evaluate long-term outcome. One hundred fifteen patients were included in therapeutic trials organized by the French Vasculitis Study Group and/or referred to our department for HBV-PAN between 1972 and 2002. To determine the frequency of HBV-PAN during the 30-year period, we analyzed a control group of patients with PAN without HBV infection, followed during the same period and diagnosed on the same bases. Depending on the year of diagnosis, different treatments were prescribed. Before the antiviral strategy was established, some patients were given corticosteroids (CS) with or without cyclophosphamide (CY). Since 1983, treatment for patients with HBV markers has combined 2 weeks of CS followed by an antiviral agent (successively, vidarabine, interferon-alpha, and lamivudine) combined with plasma exchanges (PE).Ninety-three (80.9%) patients entered remission during this period and 9 (9.7%) of them relapsed; 41 (35.7%) patients died. For the 80 patients given the antiviral strategy as intention-to-treat, 4 (5%) relapsed and 24 (30%) died vs 5 (14.3%) relapses (not significant [NS]) and 17 (48.6%) deaths (NS) among the 35 patients treated with CS alone or with CY or PE. HBe-anti-HBe seroconversion rates for the 2 groups, respectively, were: 49.3% vs 14.7% (p < 0.001). Patients who seroconverted obtained complete remission and did not relapse.Thus, HBV-PAN, a typical form of classic PAN, can be characterized as follows: when renal involvement is present, so is renal vasculitis; glomerulonephritis due to vasculitis is never found; antineutrophil cytoplasmic antibodies (ANCA) are not detected; relapses are rare, and never occur once viral replication has stopped and seroconversion has been obtained. Combining an antiviral drug with PE facilitates seroconversion and prevents the development of long-term hepatic complications of HBV infection. The major cause of death is gastrointestinal tract involvement. Importantly, the frequency of HBV-PAN has decreased in relation to improved blood safety and vaccination campaigns.

Adult↗

PubMed2001

The genome sequence and evolution of baculoviruses.

Comparative analysis of the complete genome sequences of 13 baculoviruses revealed a core set of 30 genes, 20 of which have known functions. Phylogenetic analyses of these 30 genes yielded a tree with 4 major groups: the genus Granulovirus (GVs), the group I and II lepidopteran nucleopolyhedroviruses (NPVs), and the dipteran NPV, CuniNPV. These major divisions within the family Baculoviridae were also supported by phylogenies based on gene content and gene order. Gene content mapping has revealed the patterns of gene acquisitions and losses that have taken place during baculovirus evolution, and it has highlighted the fluid nature of baculovirus genomes. The identification of shared protein phylogenetic profiles provided evidence for two putative DNA repair systems and for viral proteins specific for infection of lymantrid hosts. Examination of gene order conservation revealed a core gene cluster of four genes, helicase, lef-5, ac96, and 38K(ac98), whose relative positions are conserved in all baculovirus genomes.

Animals↗

PubMed2001

The evolution of mycobacterial pathogenicity: clues from comparative genomics.

Comparative genomics, and related technologies, are helping to unravel the molecular basis of the pathogenesis, host range, evolution and phenotypic differences of the slow-growing mycobacteria. In the highly conserved Mycobacterium tuberculosis complex, where single-nucleotide polymorphisms are rare, insertion and deletion events (InDels) are the principal source of genome plasticity. InDels result from recombinational or insertion sequence (IS)-mediated events, expansion of repetitive DNA sequences, or replication errors based on repetitive motifs that remove blocks of genes or contract coding sequences. Comparative genomic analyses also suggest that loss of genes is part of the ongoing evolution of the slow-growing mycobacterial pathogens and might also explain how the vaccine strain BCG became attenuated.

Amino Acid Sequence↗

PubMed1999

Estimation and comparison of rates of change in longitudinal studies with informative drop-outs.

Many cohort studies and clinical trials have designs which involve repeated measurements of disease markers. One problem in such longitudinal studies, when the primary interest is to estimate and to compare the evolution of a disease marker, is that planned data are not collected because of missing data due to missing visits and/or withdrawal or attrition (for example, death). Several methods to analyse such data are available, provided that the data are missing at random. However, serious biases can occur when missingness is informative. In such cases, one needs to apply methods that simultaneously model the observed data and the missingness process. In this paper we consider the problem of estimation of the rate of change of a disease marker in longitudinal studies, in which some subjects drop out prematurely (informatively) due to attrition, while others experience a non-informative drop-out process (end of study, withdrawal). We propose a method which combines a linear random effects model for the underlying pattern of the marker with a log-normal survival model for the informative drop-out process. Joint estimates are obtained through the restricted iterative generalized least squares method which are equivalent to restricted maximum likelihood estimates. A nested EM algorithm is applied to deal with censored survival data. The advantages of this method are: it provides a unified approach to estimate all the model parameters; it can effectively deal with irregular data (that is, measured at irregular time points), a complicated covariance structure and a complex underlying profile of the response variable; it does not entail such complex computation as would be required to maximize the joint likelihood. The method is illustrated by modelling CD4 count data in a clinical trial in patients with advanced HIV infection while its performance is tested by simulation studies.

Biomarkers↗

PubMed2004

Enhanced axonal growth into a spinal cord contusion injury site in a strain of mouse (129X1/SvJ) with a diminished inflammatory response.

After injury in the adult central nervous system, invading and intrinsic cells contribute to the formation of a lesion site that is refractory to axonal growth. To test the hypothesis that the inflammatory response to trauma dictates the extent of axonal growth after spinal cord injury, the time course of lesion evolution was compared in two mouse strains with contrasting cellular responses to peripheral inflammatory challenge. Adult C57Bl/6 and 129X1/SvJ mice received identical contusion injuries to the mid-thoracic spinal cord and were allowed to recover for 6 hours to 9 weeks. Both strains responded with a rapid, transient increase in chemokine expression, but the magnitude of this early response was slightly reduced in the 129X1/SvJ mice. Morphological indicators of inflammation were similar during the first week postinjury. After 7 days postinjury, however, the cellular responses differed between strains. The C57Bl/6 lesion core was chronically occupied by macrophages, devoid of astrocytes, and contained few axonal profiles. In contrast, as the macrophage density decreased a network of astrocytic processes and axons of central and peripheral origin invaded the center of the lesion site in 129X1Sv/J mice. Growth of axons in the 129X1Sv/J mice was accompanied by increased extravascular laminin in the lesion core and a reduced expression of chondroitin sulfate proteoglycan glycosaminoglycan sidechains in the periphery of the lesion. These results demonstrate that the diminished chronic inflammatory response in 129X1/SvJ mice is associated with enhanced cellular repair and increased axonal growth after spinal cord injury.

Animals↗

PubMed2003

Morphological changes on small-bowel fetal allografts in mice.

The aim of this study was to evaluate the early morphological development and acute rejection process in fetal intestine allografts. Grafts from C57BL/6 fetal intestines were implanted in an avascular form in BALB/C recipients. A syngeneic group of animals was used to compare the evolution. The allogeneic recipients were distributed in 6 groups, according to the day of sacrifice (3rd, 4th, 5th, 6th, 7th, and 10th postoperational day (POD)) and the control group on the 2nd, 5th, and 7th POD. These grafts were stained with hematoxylin and eosin for histological evaluation, in agreement with the classification of Auber et al. (Chirurgie 123:122-130, 1998). Data showed a progressive development of the graft until POD 5. On POD 3 and 4, a top grade of development and an initial rejection were observed. From POD 5-7 and on POD 10, the acute rejection reaction was more important than the development process. The higher level of rejection was observed on POD 10, and it was similar to the 7th POD. Our results showed good graft development until POD 5. After that, the acute rejection response impeded analysis of the development process.

Animals↗

PubMed2005

An on-line technique for monitoring propionic acid fermentation.

An on-line technique, based on measuring the increase in pressure due to CO(2) release in a closed air-tight reactor, was used to evaluate the fermentation of lactate by propionibacteria. The method was applied to batch cultures of Propionibacterium shermanii grown in yeast extract/sodium lactate medium containing lactate as a carbon source under micro-aerophilic conditions. Gas pressure evolution was compared both with substrate consumption and metabolites production and with acidification and growth. Linear relationships were found between gas pressure variation, lactate consumption and propionate and acetate production. The technique also enabled the evaluation of total CO(2) produced, by taking account of pressure, oxygen and pH measurements. These results tend to show that this simple and rapid method could be useful to monitor propionic acid bacteria growth.

Acetates↗

PubMed2002

A novel subtilisin-like serine protease from Thermoanaerobacter yonseiensis KB-1: its cloning, expression, and biochemical properties.

A gene, tayI, encoding a novel subtilisin-like protease, designated thermicin, from the extremely thermophilic bacterium Thermoanaerobacter yonseiensis KB-1 (DSM 13777) was cloned by using a sequence tag containing the consensus sequence of proteases. The gene consisted of 1,239 nucleotides, and the deduced amino acid sequence indicated that it is a preproenzyme with a 311-residue mature protein composed of canonical catalytic residues (Asp29, His64, and Ser252). Thermicin was overproduced in E. coli as a fusion protein with a histidine tag and purified by nickel nitrilotriacetic acid affinity chromatography. Thermicin from E. coli showed maximum proteolytic activity at 92.5 degrees C and pH 9.0, and its half-life was 30 h at 80 degrees C. In order to determine cleavage specificity, thermicin was incubated with insulin beta chain, and the resulting peptides were analyzed by matrix assisted laser desorption/ionization-time of flight mass spectrometry. The carboxyl group side of the Val12, Leu15,17, Gly23, and Pro28 residues was cleaved. Thermicin is well known to hydrolyze Gly- and Pro-rich collagens. The K (m) and k (cat)/ K (m) values of thermicin for the hydrolysis of the synthetic substrate L-Gly-Pro- p-nitroaniline were 54.16 microM and 142.05 (10(5) s(-1) M(-1)), respectively, at 92.5 degrees C and pH 9.0. Amino acid sequence comparison and phylogenetic analysis indicated that this enzyme belongs to a new subgroup with respect to its molecular evolution, when compared with previously characterized subtilisins. This result indicates that thermicin is a novel enzyme different from other thermostable proteases.

Amino Acid Sequence↗

PubMed2005

Why disease persists: an evolutionary nosology.

Although natural selection might be expected to reduce the incidence and severity of disease, disease persists. Natural selection leads to increases in the mean fitness of populations and so will reduce the frequency of disease-associated alleles, but other evolutionary processes, such as mutation and gene flow, may introduce or increase the frequency of these deleterious alleles. The pleiotropic actions of genes and the epistatic interactions between them complicate the relationship between genotype and phenotype, and may result in the preservation of disease-associated alleles. Deleterious alleles may also be maintained because of linkage to beneficial alleles. The inability of natural selection to eliminate diseases of aging is a reminder that fitness -- success in producing progeny, or in contributing genes to the population gene pool -- is not equivalent to the absence of disease. Nutritional or psychosocial cues may lead to life history strategies that maximize survival to reproductive maturity at the expense of disease later in life. Natural selection acts on genes, cells, and groups, as well as on organisms; the outcome of evolution reflects selection at different levels of biological organization. Finally, the human environment is constantly changing, largely because of the evolution of our parasites and because of changes in cultural beliefs and practices; genetic evolution is comparatively slow and lags behind environmental change. An evolutionary nosology complements traditional medical nosologies and enhances our understanding of the persistence of disease and the meaning of human variation.

Environment↗