Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans

Recent studies of mitochondrial DNA (mtDNA) variation in mammals and Drosophila have shown an excess of amino acid variation within species (replacement polymorphism) relative to the number of silent and replacement differences fixed between species. To examine further this pattern of nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5 genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans. Of interest are the frequency spectra of silent and replacement polymorphisms, and potential variation among genes and taxa in the departures from neutral expectations. The Drosophila ND3 and ND5 data show no significant excess of replacement polymorphism using the McDonald-Kreitman test. These data are in contrast to significant departures from neutrality for the ND3 gene in mammals and other genes in Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however, both Drosophila and human mtDNA show very significant excesses of amino acid polymorphism. Silent polymorphisms at ND5 show a significantly higher variance in frequency than replacement polymorphisms, and the latter show a significant skew toward low frequencies (Tajima's D = -1.954). These patterns are interpreted in light of the nearly neutral theory where mildly deleterious amino acid haplotypes are observed as ephemeral variants within species but do not contribute to divergence. The patterns of polymorphism and divergence at charge-altering amino acid sites are presented for the Drosophila ND5 gene to examine the evolution of functionally distinct mutations. Excess charge-altering polymorphism is observed at the carboxyl terminal and excess charge-altering divergence is detected at the amino terminal. While the mildly deleterious model fits as a net effect in the evolution of nonrecombining mitochondrial genomes, these data suggest that opposing evolutionary pressures may act on different regions of mitochondrial genes and genomes.      

The Mio-Pliocene European primate fossil record: dynamics and habitat tracking

We present here a study of European Neogene primate occurrences in the context of changing humidity. We studied the differences of primate localities versus non-primate localities by using the mammal communities and the ecomorphological data of the taxa present in the communities. The distribution of primates is influenced by humidity changes during the whole Neogene, and the results suggest that the primates track the changes in humidity through time. The exception to this is the Superfamily Cercopithecoidea which shows a wider range of choices in habitats. All primate localities seem to differ from non-primate localities in that the mammal community structure is more closed habitat oriented, while in non-primate localities the community structure changes towards open-habitat oriented in the late Neogene. The differences in primate and non-primate localities are stronger during the times of deep environmental change, when primates are found in their preferred habitats and non-primate localities have faunas better able to adapt to changing conditions.     

THE IMPACT OF REGIONAL CLIMATE ON THE EVOLUTION OF MAMMALS: A CASE STUDY USING FOSSIL HORSES

One of the classic examples of faunal turnover in the fossil record is the Miocene transition from faunas dominated by anchitheriine horses with low-crowned molar teeth to faunas with hipparionine horses characterized by high-crowned teeth. The spread of hipparionine horses is associated with increased seasonality and the expansion of open habitats. It is generally accepted that anchitheriine horses did not display an evolutionary increase in tooth crown height prior to their extinction. Nevertheless, to test whether anchitheriines showed any changes interpretable as adaptation to local conditions, we analyzed molar teeth from multiple populations of Anchitherium in three dimensions. Our results show differences in tooth morphology that suggest incipient hypsodonty in Spain, the first region experiencing increasingly arid conditions in the early Miocene of Europe. Furthermore, analyses of tooth wear show that Spanish specimens cluster with present ungulates that eat foliage together with grasses and shrubs, whereas German specimens cluster with present-day ungulates that eat mostly foliage. Taken together, even a taxon such as Anchitherium , with a long and successful history of forest adaptation, did respond to regional environmental changes in an adaptive manner.     

Biomine: predicting links between biological entities using network models of heterogeneous databases

ABSTRACT: BACKGROUND: Biological databases contain large amounts of data concerning the functions and associationsof genes and proteins. Integration of data from several such databases into a single repositorycan aid the discovery of previously unknown connections spanning multiple types ofrelationships and databases. RESULTS: Biomine is a system that integrates cross-references from several biological databases into agraph model with multiple types of edges, such as protein interactions, gene-diseaseassociations and gene ontology annotations. Edges are weighted based on their type,reliability, and informativeness. We present Biomine and evaluate its performance in linkprediction, where the goal is to predict pairs of nodes that will be connected in the future,based on current data. In particular, we formulate protein interaction prediction and diseasegene prioritization tasks as instances of link prediction. The predictions are based on aproximity measure computed on the integrated graph. We consider and experiment withseveral such measures, and perform a parameter optimization procedure where different edgetypes are weighted to optimize link prediction accuracy. We also propose a novel method fordisease-gene prioritization, defined as finding a subset of candidate genes that cluster togetherin the graph. We experimentally evaluate Biomine by predicting future annotations in thesource databases and prioritizing lists of putative disease genes. CONCLUSIONS: The experimental results show that Biomine has strong potential for predicting links when aset of selected candidate links is available. The predictions obtained using the entire Biominedataset are shown to clearly outperform ones obtained using any single source of data alone,when different types of links are suitably weighted. In the gene prioritization task, anestablished reference set of disease-associated genes is useful, but the results show that underfavorable conditions, Biomine can also perform well when no such information is available.The Biomine system is a proof of concept. Its current version contains 1.1 million entities and8.1 million relations between them, with focus on human genetics. Some of its functionalitiesare available in a public query interface at http://biomine.cs.helsinki.fi, allowing searching forand visualizing connections between given biological entities.     

A radioimmunoprecipitation method in the serodiagnosis of HIV infection: the development of the optimal conditions for its performance and the evaluation of the possibilities for its use

The optimum conditions for using the method of radioimmunoprecipitation (RIP) for the detection of human immunodeficiency virus (HIV) in serum samples have been established. Out of several available cell lines persistently infected with HIV, specially selected line 17 has been chosen. The characteristic feature of this is the high and stable (under the conditions of prolonged cultivation) accumulation of virus-specific proteins in infected cells. The optimum conditions for making the test and its evaluation have also been established. The data of literature on the advantages of the method of RIP over such traditional methods as the enzyme immunoassay and immunoblotting have been confirmed. Thus, the presence of specific antibodies in several serum samples registered as false negative has been established. The intertypical reactivity of two serotypes of the virus, HIV-1 and HIV-2, has been studied. Cross reactivity of antibodies with respect to the HIV gene gag, but not with respect to viral glycoproteids, has been established. Ideas on the expediency and prospects of using RIP for the serological control of HIV infection are presented.     

Clusterings should not be compared by visual inspection: response to Gagné & Proulx

In Heikinheimo et al . ( Journal of Biogeography , 2007, 34 , 1053–1064) we used clustering to analyse European land mammal fauna. Gagné & Proulx criticized our choice of the Euclidean distance measure in the analysis, and advocated the use of the Hellinger distance measure, claiming that this leads to very different clustering results. The criticism fails to take into account the probabilistic nature of the methods used and the fact that in this case the similarity measures correlate strongly. Gagné & Proulx used subjective inspection as the criterion of similarity between clusterings. We show that this is insufficient and misleading. Namely, owing to the local minimum problem, two clustering runs rarely give identical results. In the case of our study, the measured similarity (using the kappa statistic) between the Euclidean- and Hellinger-based clusterings is roughly equal to the similarity between two clusterings that both use the Hellinger distance but different random initialization points.