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PubMed2003

The power and promise of population genomics: from genotyping to genome typing.

Population genomics has the potential to improve studies of evolutionary genetics, molecular ecology and conservation biology, by facilitating the identification of adaptive molecular variation and by improving the estimation of important parameters such as population size, migration rates and phylogenetic relationships. There has been much excitement in the recent literature about the identification of adaptive molecular variation using the population-genomic approach. However, the most useful contribution of the genomics model to population genetics will be improving inferences about population demography and evolutionary history.

Genetics, Population↗
PubMed2005

Neutral mutation as the source of genetic variation in life history traits.

The mechanism underlying the maintenance of adaptive genetic variation is a long-standing question in evolutionary genetics. There are two concepts (mutation-selection balance and balancing selection) which are based on the phenotypic differences between alleles. Mutation - selection balance and balancing selection cannot properly explain the process of gene substitution, i.e. the molecular evolution of quantitative trait loci affecting fitness. I assume that such loci have non-essential functions (small effects on fitness), and that they have the potential to evolve into new functions and acquire new adaptations. Here I show that a high amount of neutral polymorphism at these loci can exist in real populations. Consistent with this, I propose a hypothesis for the maintenance of genetic variation in life history traits which can be efficient for the fixation of alleles with very small selective advantage. The hypothesis is based on neutral polymorphism at quantitative trait loci and both neutral and adaptive gene substitutions. The model of neutral - adaptive conversion (NAC) assumes that neutral alleles are not neutral indefinitely, and that in specific and very rare situations phenotypic (relative fitness) differences between them can appear. In this paper I focus on NAC due to phenotypic plasticity of neutral alleles. The important evolutionary consequence of NAC could be the increased adaptive potential of a population. Loci responsible for adaptation should be fast evolving genes with minimally discernible phenotypic effects, and the recent discovery of genes with such characteristics implicates them as suitable candidates for loci involved in adaptation.

Alleles↗
PubMed2004

Emericella astellata, a new producer of aflatoxin B, B and sterigmatocystin.

AIMS: To report on aflatoxin B(1) and B(2) production from a species of Emericella. METHODS AND RESULTS: Aflatoxins and sterigmatocystin were determined by high-pressure liquid chromatography (HPLC) with diode array detection and confirmed by HPLC with mass spectrometry detection. Among 30 known species of Emericella only one species produced aflatoxin. Strains originating from the same geographical source material had different patterns of aflatoxin and sterigmatocystin production on different media, indicating that epigenetic factors may be involved in the regulation of aflatoxin production. However, two cultures from the same original genet were very similar. CONCLUSIONS: Emericella astellata can produce small amounts of sterigmatocystin and aflatoxin B(1) and B(2). SIGNIFICANCE AND IMPACT OF THE STUDY: Emericella has been used extensively in genetic studies and therefore the isolates producing aflatoxin can be used to elucidate the genetic, evolutionary and maybe ecological role of aflatoxins using molecular genetic methods.

Aflatoxin B1↗
PubMed1993

Co-operation and defection: playing the field in virus dynamics.

A previous model (Szathmáry, 1992) is further developed for the dynamics of standard (V) and defective interfering (DI) viruses. The crucial retained element is the incorporation of population structure in the form of a complete distribution of cells infected by particles differing in number. New elements are: the non-linear shared benefit from the contribution of Vs to the group of viruses infecting the same cell (synergistic at low numbers, diminishing returns at high numbers, respectively); a dynamics for the total number of particles (V and DI); and the possibility of extinction if the frequency of Vs is small enough. In evolutionary genetical terms this is a frequency- and density-dependent evolutionary game. A crucial result is retained: coexistence of Vs and DIs is possible provided the multiplicity of infection (hence the size of the coinfection group) is large enough. Phase portraits and vector-field plots for a continuous-time and numerical solutions for a corresponding discrete-time case are presented. The latter reflect the basic features of serial, undiluted passage. The causes for two possible means of extinction (low initial frequency of Vs, and very high vigour of Vs) are revealed: the appearance of high amplitude fluctuations. Coexistence can apparently be ensured by stable points, periodic behaviour, or strange attractors. The paper clarifies the dynamical background of cycles found experimentally in V-DI systems.

Biological Evolution↗
PubMed2006

QTL analysis of behavioral and morphological differentiation between wild and laboratory zebrafish (Danio rerio).

The zebrafish is an important model organism for neuro-anatomy and developmental genetics. It also offers opportunities for investigating the functional and evolutionary genetics of behaviour but these have yet to be exploited. The ecology of anti-predator behaviour has been widely studied in fish and has been shown to vary among populations and between wild and domesticated (laboratory) fish. Here, we utilise the strong behavioural differences present between a wild-derived strain of fish from Bangladesh and the laboratory strain AB. In total, 184 F2 fish were generated and tested for shoaling tendency and willingness to approach an unfamiliar object ('boldness'). Our results indicate the existence of QTL for boldness on chromosomes 9 and 16 and suggest another genomic region that influences anti-predator behaviour on chromosome 21. QTL for growth rate, weight and fat content, all of which are elevated in laboratory fish, were detected on chromosome 23. These initial results confirm the potential for QTL mapping of behavioural traits in zebrafish and also for dissecting the consequences of selection during domestication.

Animals↗
PubMed2003

Unusual pattern of single nucleotide polymorphism at the exuperantia2 locus of Drosophila pseudoobscura.

We have investigated the pattern of DNA sequence variation at the exuperantia2 locus in Drosophila pseudoobscura. This adds to the increasing dataset of genetic variation in D. pseudoobscura, a useful model species for evolutionary genetic studies. The level of silent site nucleotide diversity and the divergence from an outgroup Drosophila miranda are comparable with those for other X-linked loci. One peculiar pattern at the exu2 locus of D. pseudoobscura is a complete linkage disequilibrium between two SNPs, one of which is a replacement site. As a result, there are two distinct haplotype groups in our dataset. Based upon the comparisons with the outgroup sequences from D. miranda and Drosophila persimilis, we show that the newly derived haplotype group has lower diversity than the ancestral haplotype group. The pattern of protein evolution at exu2 shows some deviation from the neutral model. Together, these and other characteristics of the exu2 locus suggest the action of selection on the pattern of SNP variation, consistent with a partial selective sweep associated with the newly derived haplotype.

Animals↗
PubMed2002

Antioxidant gene expression in active and sedentary house mice (Mus domesticus) selected for high voluntary wheel-running behavior.

We present liver mRNA levels of the two antioxidant enzymes catalase (CAT) and Mn-superoxide dismutase (SOD2) in four treatment groups of house mice assayed by RNase protection at 20 months of age. These groups were mice from four replicate selection and four replicate control lines from the sixteenth generation of selective breeding for high voluntary wheel running, housed with or without running wheels from age 3 weeks through 20 months. Exercising control females had induced CAT expression; SOD2 exhibited a similar pattern in females from two of the four control lines. Exercising male mice had induced CAT expression, but not SOD2 expression, irrespective of genetic background. We discuss these results with respect to both evolutionary (genetic) and training (exercise-induced) adaptations and explore predictions of these results in relation to the oxidative-damage theory of senescence.

Aging↗
PubMed2004

Conserved genetic basis of a quantitative plumage trait involved in mate choice.

A key question in evolutionary genetics is whether shared genetic mechanisms underlie the independent evolution of similar phenotypes across phylogenetically divergent lineages. Here we show that in two classic examples of melanic plumage polymorphisms in birds, lesser snow geese (Anser c. caerulescens) and arctic skuas (Stercorarius parasiticus), melanism is perfectly associated with variation in the melanocortin-1 receptor (MC1R) gene. In both species, the degree of melanism correlates with the number of copies of variant MC1R alleles. Phylogenetic reconstructions of variant MC1R alleles in geese and skuas show that melanism is a derived trait that evolved in the Pleistocene.

Animals↗
PubMedDate not supplied

Construction of genetic code from evolutionary stability.

The construction of the genetic code is investigated based on a stability principle. The concept and formulation of mutational deterioration (MD) of the genetic code is proposed. It is proved that the degeneracies of codon multiplets obey the rule to best resist MD. The MD for each ideal multiplet of codons is expressed by four parameters and it takes on a minimum value for real distributions of codons in the multiplet. Then the global mutational deterioration (GMD) of code table is calculated and the minimal code is deduced. The domain-like distribution of hydrophobic and hydrophilic amino acids on the genetic code is explained from the minimization of GMD. It is demonstrated that the standard code is approximately GMD-minimal. By introducing some constraints that are related to the initial condition of the system, we have deduced the standard genetic code from the minimization of GMD. The minimization shows the general trend of evolutionary process to some stable state while the constraints reflect a 'frozen accident.' Many deviant codon assignments are also explained through MD minimization assuming the changeable degrees of degeneracies for some multiplets. So, a possible answer to the question of "Why are synonymous codons and amino acids distributed in the code table just as they are?" is given.

Biological Evolution↗
PubMed2004

Negative effect of genetic bottlenecks on the adaptability of vesicular stomatitis virus.

Muller's ratchet is a principle of evolutionary genetics describing mutant accumulation in populations that are repeatedly subjected to genetic bottleneck. The immediate effect of Muller's ratchet, overall loss of fitness, has been confirmed in several viral systems belonging to different groups. This report shows that in addition to fitness loss, genetic bottlenecks also have longer-term effects, namely changes in the capacity of viral populations to adapt. Thus, vesicular stomatitis virus strains with a history of genetic bottleneck have lower adaptability than strains maintained at relatively large population sizes. This lower adaptability is illustrated by their reduced ability to regain fitness and by their inability to outcompete wild-type populations in situations where the initial fitness of the bottlenecked mutant is the same or even higher than the initial fitness of the wild-type.

Animals↗
PubMed1996

Aging mechanisms in fruit files.

Genetic analysis of Drosophila has provided evidence in support of two proposed evolutionary genetic mechanisms of aging: mutation accumulation and antagonistic pleiotropy. Both mechanisms result from the lack of natural selection acting on old organisms. Analyses of large numbers of files have revealed that mortality rates do not continue to rise with age as previously thought, but plateau at advanced ages. This phenomenon has implications both for models and for definitions of aging, and may be explained by the evolutionary theories. The physiological processes and genes most relevant to aging are being identified using Drosophila lines selected in the laboratory for postponed senescence. Oxidative stress and insufficient metabolic reserves/capacity may be particularly important factors in limiting the fruitfly lifespan. Genes which exhibit aging-related changes in expression are now being identified. Transgenic files are being used to analyze the mechanisms of such aging-related gene expression, and to test the effects of specific genes on aging and aging-related deterioration.

Aging↗
PubMed1998

Genetic epidemiology of parasitic protozoa and other infectious agents: the need for an integrated approach.

This paper emphasises the relevance of the concepts and methods of evolutionary genetics for studying the epidemiology of parasitic protozoa and other pathogenic agents. Population genetics and phylogenetic analysis both contribute to identifying the relevant evolutionary and epidemiologically discrete units of research (Discrete typing units = DTUs), that can be equated to distinct phylogenetic lines. It is necessary (i) to establish that a given species represents a reliable DTU; (ii) to see whether a given species is further structured into lower DTUs that correspond to either clonal lineages or to cryptic species, and could exhibit distinct biomedical properties (virulence, resistance to drugs, etc). DTUs at the species and subspecies level can be conveniently identified by specific genetic markers or sets of genetic markers ("tags") for epidemiological follow-up. For any kind of pathogen (protozoa, fungi, bacteria, viruses), DTUs represent the relevant units of research, not only for epidemiology, but also, for other applied researches (clinical study, pathogenicity, vaccine and drug design, immunology, etc). The development of an "integrated genetic epidemiology of infectious diseases", that would explore the respective role of, and the interactions between, the genetic diversity (and its biological consequences) of the pathogen, the host and the vector (in the case of vector-borne diseases) is called for.

Animals↗
PubMed2003

'Genotypic shuffling' of sequential clones of Candida albicans in HIV-infected individuals with and without symptomatic oral candidiasis.

Although HIV-infected individuals harbour multiple strains of oral Candida albicans, little is known of their micro-evolution over time. Therefore, a prospective study was conducted with 16 HIV-infected ethnic Chinese individuals with and without symptoms of oropharyngeal candidiasis to evaluate the genotype distribution of oral C. albicans isolates during HIV disease progression. Oral-rinse samples were obtained from all individuals and up to five C. albicans colonies were selected for each visit, over a 12 month period of multiple visits. After identification of isolates using standard mycological criteria, the genetic similarities of yeast isolates within and between sequential clones of C. albicans were assessed by DNA fingerprinting through random amplification of polymorphic DNA (RAPD). The results of RAPD gel profiles and the lineage of each isolate were further analysed using commercially available software. RAPD studies revealed the prevalence of up to 14 different genotypes per individual during the study period, with multiple genotypes isolated simultaneously from a single oral rinse. Computer analysis of RAPD profiles revealed that yeasts isolated over sequential visits from symptomatic individuals demonstrated a striking level of relatedness compared with isolates from asymptomatic individuals. Genetically identical C. albicans strains also formed 'loosely' connected subclusters that overlapped multiple visits, implying genetic 'shuffling' in these isolates during disease progression. These data point to varying evolutionary genetic trends in C. albicans associated with symptomatic oral candidiasis and asymptomatic carriage in HIV disease.

AIDS-Related Opportunistic Infections↗
PubMed2007

Signatures of positive selection in genes associated with human skin pigmentation as revealed from analyses of single nucleotide polymorphisms.

Phenotypic variation between human populations in skin pigmentation correlates with latitude at the continental level. A large number of hypotheses involving genetic adaptation have been proposed to explain human variation in skin colour, but only limited genetic evidence for positive selection has been presented. To shed light on the evolutionary genetic history of human variation in skin colour we inspected 118 genes associated with skin pigmentation in the Perlegen dataset, studying single nucleotide polymorphisms (SNPs), and analyzed 55 genes in detail. We identified eight genes that are associated with the melanin pathway (SLC45A2, OCA2, TYRP1, DCT, KITLG, EGFR, DRD2 and PPARD) and presented significant differences in genetic variation between Europeans, Africans and Asians. In six of these genes we detected, by means of the EHH test, variability patterns that are compatible with the hypothesis of local positive selection in Europeans (OCA2, TYRP1 and KITLG) and in Asians (OCA2, DCT, KITLG, EGFR and DRD2), whereas signals were scarce in Africans (DCT, EGFR and DRD2). Furthermore, a statistically significant correlation between genotypic variation in four pigmentation candidate genes and phenotypic variation of skin colour in 51 worldwide human populations was revealed. Overall, our data also suggest that light skin colour is the derived state and is of independent origin in Europeans and Asians, whereas dark skin color seems of unique origin, reflecting the ancestral state in humans.

Asian People↗
PubMed2003

Genome evolution in an insect cell: distinct features of an ant-bacterial partnership.

Bacteria that live exclusively within eukaryotic host cells include not only well-known pathogens, but also obligate mutualists, many of which occur in diverse insect groups such as aphids, psyllids, tsetse flies, and the ant genus Camponotus (Buchner, 1965; Douglas, 1998; Moran and Telang, 1998; Baumann et al., 2000; Moran and Baumann, 2000). In contrast to intracellular pathogens, these primary (P) endosymbionts of insects are required for the survival and reproduction of the host, exist within specialized host cells called bacteriocytes, and undergo stable maternal transmission through host lineages (Buchner, 1965; McLean and Houk, 1973). Due to their long-term host associations and close phylogenetic relationship with well-characterized enterobacteria (Fig. 1), P-endosymbionts of insects are ideal model systems to examine changes in genome content and architecture that occur in the context of beneficial, intracellular associations. Since these bacteria have not been cultured outside of the host cell, they are difficult to study with traditional genetic or physiological approaches. However, in recent years, molecular and computational approaches have provided important insights into their genetic diversity and ecological significance. This review describes some recent insights into the evolutionary genetics of obligate insect-bacteria symbioses, with a particular focus on an intriguing association between the bacterial endosymbiont Blochmannia and its ant hosts.

Animals↗
PubMed2005

Spatial dynamics and molecular ecology of North American rabies.

Rabies, caused by a single-stranded RNA virus, is arguably the most important viral zoonotic disease worldwide. Although endemic throughout many regions for millennia, rabies is also undergoing epidemic expansion, often quite rapid, among wildlife populations across regions of Europe and North America. A current rabies epizootic in North America is largely attributable to the accidental introduction of a particularly well-adapted virus variant into a naive raccoon population along the Virginia/West Virginia border in the mid-1970s. We have used the extant database on the spatial and temporal occurrence of rabid raccoons across the eastern United States to construct predictive models of disease spread and have tied patterns of emergence to local environmental variables, genetic heterogeneity, and host specificity. Rabies will continue to be a remarkable model system for exploring basic issues in the temporal and spatial dynamics of expanding infectious diseases and examining ties between disease population ecology and evolutionary genetics at both micro- and macro-evolutionary time scales.

Algorithms↗
PubMed1991

Isolation and characterization of DNA from archaeological bone.

DNA was extracted from human and animal bones recovered from archaeological sites and mitochondrial DNA sequences were amplified from the extracts using the polymerase chain reaction. Evidence is presented that the amplified sequences are authentic and do not represent contamination by extraneous DNA. The results show that significant amounts of genetic information can survive for long periods in bone, and have important implications for evolutionary genetics, anthropology and forensic science.

Animals↗
PubMed1998

Evolution of olfactomedin. Structural constraints and conservation of primary sequence motifs.

Olfactomedin is a glycosylated extracellular matrix protein originally identified at the mucociliary surface of the amphibian olfactory neuroepithelium and subsequently localized throughout the mammalian central nervous system. Although olfactomedin homologues have been identified in fish, frog, rat, mouse and human, its function is still unknown. As a first step toward elucidating the function of olfactomedin, sequences of teleost, amphibian and human homologues were compared to identify invariant, and hence, potential functionally important motifs. Previous studies revealed 33% amino acid sequence identity between rat and frog olfactomedin in their carboxyl terminal segments. Further analysis, however, reveals more extensive homologies throughout the molecule. Despite significant sequence divergence, cysteines essential for homo-polymer formation, such as the CXC motif near the amino terminus, are conserved as is the characteristic glycosylation pattern, suggesting that these posttranslational modifications are essential for function. Furthermore, alignment of a region of 53 amino acids of fish, frog, rat and human olfactomedin reveals seven invariant residues including a negatively charged cluster of aspartic and glutamic acid residues. Molecular evolutionary genetic analysis reveals an accelerated rate of nucleotide substitutions in the mammalian lineage. The evolutionary rate at the protein level, however, is constant, indicating that evolution of olfactomedin is constrained by structural limitations. Whereas considerable evolutionary divergence is evident between fish, frog and mammalian olfactomedins, olfactomedins of rat and human show 98% amino acid sequence identity. It appears that an ancestral olfactomedin gene arose before the evolution of terrestrial vertebrates and evolved independently in teleost, amphibian and mammalian lineages. The apparent evolutionary pressure toward conservation of primary structure supports the notion that olfactomedin has an important function in the mammalian nervous system.

Amino Acid Sequence↗