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Evolution of influenza A virus PB2 genes: implications for evolution of the ribonucleoprotein complex and origin of human influenza A virus.

Phylogenetic analysis of 20 influenza A virus PB2 genes showed that PB2 genes have evolved into the following four major lineages: (i) equine/Prague/56 (EQPR56); (ii and iii) two distinct avian PB2 lineages, one containing FPV/34 and H13 gull virus strains and the other containing North American avian and recent equine strains; and (iv) human virus strains joined with classic swine virus strains (i.e., H1N1 swine virus strains related to swine/Iowa/15/30). The human virus lineage showed the greatest divergence from its root relative to other lineages. The estimated nucleotide evolutionary rate for the human PB2 lineage was 1.82 x 10(-3) changes per nucleotide per year, which is within the range of published estimates for NP and NS genes of human influenza A viruses. At the amino acid level, PB2s of human viruses have accumulated 34 amino acid changes over the past 55 years. In contrast, the avian PB2 lineages showed much less evolution, e.g., recent avian PB2s showed as few as three amino acid changes relative to the avian root. The completion of evolutionary analyses of the PB1, PB2, PA and NP genes of the ribonucleoprotein (RNP) complex permits comparison of evolutionary pathways. Different patterns of evolution among the RNP genes indicate that the genes of the complex are not coevolving as a unit. Evolution of the PB1 and PB2 genes is less correlated with host-specific factors, and their proteins appear to be evolving more slowly than NP and PA. This suggests that protein functional constraints are limiting the evolutionary divergence of PB1 and PB2 genes. The parallel host-specific evolutionary pathways of the NP and PA genes suggest that these proteins are coevolving in response to host-specific factors. PB2s of human influenza A viruses share a common ancestor with classic swine virus PB2s, and the pattern of evolution suggests that the ancestor was an avian virus PB2. This same pattern of evolution appears in the other genes of the RNP complex. Antigenic studies of HA and NA proteins and sequence comparisons of NS and M genes also suggest a close ancestry for these genes in human and classic swine viruses. From our review of the evolutionary patterns of influenza A virus genes, we propose the following hypothesis: the common ancestor to current strains of human and classic swine influenza viruses predated the 1918 human pandemic virus and was recently derived from the avian host reservoir.

Amino Acid Sequence↗

The homeotic gene spalt (sal) evolved during Drosophila speciation.

The region-specific homeotic gene spalt (sal) acts in two separate domains in the head and tail region of the Drosophila melanogaster embryo. Based on comparative morphology, sal is likely to be involved in the establishment of the head during the evolution of invertebrates and thus, it should be conserved. We have analyzed the conservation of the segmentation genes Krüppel (Kr) and even-skipped (eve) in parallel with sal coding sequences in several Drosophila species that are evolutionarily separated by up to 60 million years. To our surprise, sal sequences appear to be conserved in the Sophophora subgenus of the Drosophila genus but not in the Drosophila subgenus. On the other hand, the segmentation and other homeotic genes are conserved in the Drosophila subgroup as well. Our data suggest that sal encodes an accessory function that evolved relatively late during Drosophila speciation rather than playing a fundamental evolutionary role similar to that of other homeotic genes.

Amino Acid Sequence↗

Island mammals of the past.

The effect of insularity on mammal evolution is approached by considering endemic fossil mammals of islands in the Mediterranean. It is shown that in general the same mammals will arrive on the islands by sweepstake dispersal. Among the large mammals this includes elephants, hippopotamids and deer: all mammals known for their good swimming ability. The evolutionary changes these mammals underwent follow parallel patterns on different islands and can be explained as an adaptational process to an island environment lacking large carnivores.

Animals↗

Chromosomal sex-determining regions in animals, plants and fungi.

The independent evolution of sex chromosomes in many eukaryotic species raises questions about the evolutionary forces that drive their formation. Recent advances in our understanding of these genomic structures in mammals in parallel with alternate models such as the monotremes, fish, dioecious plants, and fungi support the idea of a remarkable convergence in structure to form large, non-recombining regions with discrete evolutionary strata. The discovery that evolutionary events similar to those that have transpired in humans have also occurred during the formation of sex chromosomes in organisms as divergent as the plant Silene, the fungus Cryptococcus and the fish medaka highlights the importance of future studies in these systems. Such investigation will broaden our knowledge of the evolution and plasticity of these ubiquitous genomic features underlying sexual dimorphism and reproduction.

Animals↗

[On the evolution of voice (author's transl)].

The paper gives a short survey of the phylogenetic development of the laryngeal and supralaryngeal apparatus from amphibians to man. The increasing differentiation of vocal behaviour, paralleling the differentiation of the vocal apparatus, is outlined and special reference is made to the non-verbal component in human language. It is stressed that animal vocal repertoires can be extremely rich, but in contrast to human verbal behaviour they are generated almost exclusively by laryngeal modulations and only to a minimal degree by supralaryngeal activity (i.e. articulation). A phylogenetic development can also be seen in the cerebral organization of vocal behaviour. In amphibians, reptiles and lower mammals, the dorsal midbrain-pons transitional zone seems to be the only area responsible for the production of vocal utterances. This area probably serves in integrating vocal fold movements, expiration, intra- and extra-oral muscle activity into species-specific vocal patterns; its destruction results in mutism. In higher mammals, including man, this area does not lose its original function but is brought under the control of the cortex around the anterior sulcus cinguli (supplementary motor area and anterior cingulate gyrus). The latter seems to play an essential role in the initiation of vocal utterances in situations which do not have a rigid stimulus-response characteristic, i.e. in voluntary vocal behaviour. The highest level of voice production, finally is represented by the cortical face area, the destruction of which is without consequence to the innate vocal behaviour of animals but produces dysarthria in man. This area (together with its associated structures, such as the cortex-pontine nuclei-cerebellum-thalamus-cortex circuit) seems to be essential for the production of verbal or, more generally, learned vocal behaviour.

Amphibians↗

The genesis of neurosurgery and the evolution of the neurosurgical operative environment: part I-prehistory to 2003.

Despite its singular importance, little attention has been given to the neurosurgical operative environment in the scientific and medical literature. This article focuses attention on the development of neurosurgery and the parallel emergence of its operative setting. The operative environment has, to a large extent, defined the "state of the art and science" of neurosurgery, which is now undergoing rapid reinvention. During the course of its initial invention, major milestones in the development of neurosurgery have included the definition of anatomy, consolidation of a scientific basis, and incorporation of the practicalities of anesthesia and antisepsis and later operative technical adjuvants for further refinement of action and minimalism. The progress, previously long and laborious in emergence, is currently undergoing rapid evolution. Throughout its evolution, the discipline has assimilated the most effective tools of modernity into the operative environment, leading eventually to the entity known as the operating room. In the decades leading to the present, progressive minimalization of manipulation and the emergence of more refined operative definition with increasing precision are evident, with concurrent miniaturization of attendant computerized support systems, sensors, robotic interfaces, and imaging devices. These developments over time have led to the invention of neurosurgery and the establishment of the current state-of-the-art neurosurgical operating room as we understand it, and indeed, to a broader definition of the entity itself. To remain current, each neurosurgeon should periodically reconsider his or her personal operative environment and its functional design with reference to modernity of practice as currently defined.

History, 15th Century↗

Evolution of laboratory parameters during sickle cell painful crisis: evidence compatible with dense red cell sequestration without thrombosis.

We find that during 51 episodes of sickle cell painful crisis indirect bilirubin fell 52% from its steady state value of 2.3 +/- 1.9 mg% to a value of 1.1 +/- 0.37 mg% at the end of crisis (p less than .00000085). The indirect bilirubin decline correlates with a decrease in the dense sickle cells during crisis (r = .31, p less than .0009). During steady state, both indirect bilirubin and lactic acid dehydrogenase correlate significantly with number of dense red cells (r = .62, p less than .000002 and r = .32, p less than .02 respectively). Platelet counts, beta-thromboglobulin, Platelet Factor 4, and Fibrinopeptide A levels all were elevated during steady state and did not change during the evolution of crisis. These data demonstrate that elevated indices usually associated with platelet activation are a feature of the steady state of sickle cell disease but argue against thrombosis as a factor in the progression of a sickle cell painful crisis episode. The parallel decline of both dense cells and bilirubin during painful crises indicates that the disappearance of dense cells during crisis is not caused by hemolysis and supports the hypothesis that dense red cell sequestration, in the absence of evidence of thrombosis, is an intrinsic component of the evolution of sickle cell painful crisis.

Adult↗

Composite cis-acting epigenetic switches in eukaryotes: lessons from Drosophila Fab-7 for the Igf2-H19 imprinted domain.

One of the central problems of eukaryotic gene regulation is to understand the mechanism(s) by which the activity of enhancer elements is circumscribed such that they only act upon their cognate promoter sequences. Studies on the bithorax gene complex (BX-C) in Drosophila have highlighted the potential problem of enhancer promiscuity and detailed molecular and genetic analyses are now providing insight into how this gene complex resolves the problem through the activity of boundary/silencer elements that can block the communication between enhancers and promoters. Analysis of the mouse Igf2-H19 imprinted locus also suggests a role for boundary/silencer elements, but in this case these elements are invoked to account for the preferential expression of Igf2 and H19 from the paternally and maternally inherited chromosomes respectively despite the presence of functional downstream enhancers. We discuss recent work that has illuminated both of these systems and consider what parallels exist between them.

Animals↗

The evolutionary ethics of Alfred C. Kinsey.

It is commonplace to point out that Alfred Kinsey's taxonomic work on gall wasps provided a methodology for his studies of human sexual behavior. It is equally commonplace to point out that, when researching and presenting his sexual studies, Kinsey's professedly neutral scientific data were constrained by a social agenda. What I have done in this paper is to join these two claims and demonstrate, with particular reference to Kinsey's Sexual Behavior in the Human Male, how his zoology helped guide Kinsey to a naturalistic ethics that, despite contrasts to, shared certain parallel logical failures with the traditional ethics of his critics.

Animals↗

The HLA-DRw8 lineage was generated by a deletion in the DR B region followed by first domain diversification.

Sequences were generated for the first, second, and 3'UT regions of DRw8 beta-chain genes from two cell lines differing in their T cell determined allospecificities. Both have second domain sequences homologous to the B1 locus of the DRw52 family (DR3, DR5, and DRw6) and not the B3 locus. However, the 3'UT sequence is homologous to the 3'UT region of the B3 locus of the DRw52 family, and not the B1 locus. The first domain sequences are B1-like as opposed to B3-like and show polymorphism in the region encoding the putative alpha-helical region of the DR beta-chain. The easiest interpretation is that the DRw8 haplotypes constitute a sublineage within the DRw52 group and that this lineage has arisen by a small chromosomal deletion of the region between the B1 locus and the B3 locus. This deletion included the 3'UT region of the B1 locus, the B2 pseudogene, and the 5' end of the B3 locus including the exons encoding the first and second domains. After the deletion, two changes in the first domain arose by a mutational mechanism, possibly gene conversion. One of these changes parallels one seen in the DRw11 lineage.

Amino Acid Sequence↗

[Anatomical variations and taxonomic relatedness in Hominoidea].

31 anatomical variations were examined in 125 Pan paniscus and 96 Gorilla gorilla beringei skulls. Comparisons with published data of Hominoidea show that differences in their frequencies are proportional and parallel to taxonomic relationships on the subspecific, specific and generic level.

Animals↗

Evolution of feeding niches in New World monkeys.

The adaptive radiation of modern New World monkeys unfolded as the major lineages diversified within different dietary-adaptive zones predicated upon a fundamentally frugivorous habit. The broad outlines of this pattern can be seen in the fossil record, beginning in the early Miocene. Cebids are obligate frugivorous predators. The smallest forms (Cebuella, Callithrix) are specialized exudativores, and the largest (cebines) are seasonally flexible omnivores, feeding particularly on insects (Saimiri) or "hard" foods, such as pith and palm nuts (Cebus), when resources are scarce. The smaller-bodied atelids (Callicebus, Aotus) may use insects or leaves opportunistically, but pitheciins (saki-uakaris) specialize on seeds as their major protein source. The larger atelines (Alouatta, Brachyteles) depend on leaves or on ripe fruit (Ateles). Locomotion, body size, and dietary adaptations are linked: claws and small body size opened the canopy-subcanopy niche to callitrichines; climbing and hanging, the fine-branch setting to the atelines; large size and strength, semiprehensile tails, and grasping thumbs, the extractive insectivory of Cebus; deliberate quadrupedalism, the energy-saving transport of folivorous Alouatta. Body size increases and decreases occurred often and in parallel within guilds and lineages. Conventional dietary categories, particularly frugivory, are inadequate for organizing the behavioral and anatomical evidence pertinent to evolutionary adaptation. Related models of morphological evolution based on feeding frequencies tend to obfuscate the selective importance of "critical functions," responses to the biomechanically challenging components of diet that may be determined by a numerically small, or seasonal, dietary fraction. For fossils, body size is an unreliable indicator of diet in the absence of detailed morphological information. More attention needs to be given to developing techniques for identifying and quantifying mechanically significant aspects of dental form, the physical properties of primate foods, their mode of access, and the cycles of availability and nutritional value.

Adaptation, Physiological↗

Combinatorial and Evolution-Based Methods in the Creation of Enantioselective Catalysts.

Combinatorial methods in the development of enantioselective homogeneous catalysts constitute a new branch of catalysis research. The goal is to prepare libraries of potential asymmetric catalysts, rather than choosing the traditional one-catalyst-at-a-time approach. Several conceptional advancements have been reported in the parallel preparation of chiral ligands. Currently the most meaningful systems constitute modularly constructed ligands on solid supports, which allow high degrees of structural diversity and thus the maximum probability of finding enantioselective catalysts or even new types of ligands for asymmetric catalysis. Search strategies have been developed which amongst other things, lead to catalysts not likely to have been discovered by traditional methods. Genuine application of such strategies involve thousands of catalysts and require high-throughput screening systems capable of assaying enantioselectivity. The first high-throughput ee-screening systems were in fact developed for use in the directed evolution of enantioselective enzymes, a process based on "evolution in the test tube" in which the appropriate methods of random mutagenesis, gene expression, and ee assays are combined. Since no screening system is likely to be universal, different approaches are necessary. Thus far these include assays based on UV/Vis, fluorescence, circular dichroism, mass spectrometry, and even modified gas chromatography as well as special forms of capillary electrophoresis. One of the most efficient systems involves the concept of the mass-spectrometric detection of deuterium-labeled pseudo-enantiomers and pseudo-prochiral compounds with which about 1000 exact ee determinations can be achieved per day, although the assay is restricted to kinetic resolution and/or reactions of prochiral compounds bearing enantiotopic groups. Super-high-throughput screening for enantioselectivity is possible in many cases by making use of chirally modified capillary array electrophoresis in a parallel step. Accordingly, 7000 to 30 000 ee determinations can be carried out per day. These and other analytical developments are expected to stimulate further research in the combinatorial search for asymmetric homogeneous catalysts and in the directed evolution of enantioselective enzymes for use in organic chemistry.

Journal Article↗

The use of amino acid sequence analysis in assessing evolution.

The thirteen year history of assessing evolution by amino acid sequence analysis has made apparent the limitations imposed upon this system by the finite nature of the characters. This finiteness exists on several levels and ultimately expresses itself as parallelism, back mutation and the retention of primitive characters in the sequences of proteins from present day species and the putative ancestral protein chains. Sequence analysis shares these problems with other molecular approaches, but because it is concerned both with the nucleotide substitutions in the genome and with the functional roles of proteins, it has unique advantages. For example, the large fluctuation in the rate of fixation of mutations in a protein's evolution can be detected and used to point out the unreliability of any molecular clock for estimating divergence dates. Moreover, when consideration is given to studies which assign functional significance to specific amino acid sites in a protein, changes in function during the descent of a protein can be appreciated and their significance correlated with organismal evolution.

Amino Acid Sequence↗

Protein dispensability and rate of evolution.

If protein evolution is due in large part to slightly deleterious amino acid substitutions, then the rate of evolution should be greater in proteins that contribute less to individual fitness. The rationale for this prediction is that relatively dispensable proteins should be subject to weaker purifying selection, and should therefore accumulate mildly deleterious substitutions more rapidly. Although this argument was presented over twenty years ago, and is fundamental to many applications of evolutionary theory, the prediction has proved difficult to confirm. In fact, a recent study showed that essential mouse genes do not evolve more slowly than non-essential ones. Thus, although a variety of factors influencing the rate of protein evolution have been supported by extensive sequence analysis, the relationship between protein dispensability and evolutionary rate has remained unconfirmed. Here we use the results from a highly parallel growth assay of single gene deletions in yeast to assess protein dispensability, which we relate to evolutionary rate estimates that are based on comparisons of sequences drawn from twenty-one fully annotated genomes. Our analysis reveals a highly significant relationship between protein dispensability and evolutionary rate, and explains why this relationship is not detectable by categorical comparison of essential versus non-essential proteins. The relationship is highly conserved, so that protein dispensability in yeast is also predictive of evolutionary rate in a nematode worm.

Amino Acid Substitution↗

Cytokines in mammalian reproduction and speculation about their possible involvement in nonmammalian viviparity.

In recent years, the secretion of immunoregulatory factors (cytokines) at the maternofetal interface in mammals has been widely documented. Although cytokine production seems to be a specific phenomenon in mammalian reproduction, the specific roles of these substances in different species are still not clear. However, a balance of different cytokine activities appears to be crucial for regulation of the establishment and survival of the semiallogeneic embryo in maternal tissues. The apparent immunological role of placental cytokines in the mechanisms of implantation and embryonic development in mammals has raised the question of whether cytokines are also involved in the reproduction of nonmammalian vertebrates. Our studies have shown that the production of cytokines by the maternofetal unit is not limited to mammalian species, but that interleukin-1 (IL-1)alpha, IL-1beta, and transforming growth factor-beta (TGF-beta) are secreted by the placenta of a viviparous squamate reptile, Chalcides chalcides. Our finding of this parallelism between reptilian and mammalian reproduction suggests that immunological mechanisms, possibly mediated by the secretion of cytokines, played an important role in the evolution of viviparity.

Animals↗

The Human Genome Project--an overview.

The human genome sequence will underpin human biology and medicine in the next century, providing a single, essential reference to all genetic information. The international program to determine the complete DNA sequence (3,000 million bases) is well underway. As of January 2000, 50% of the sequence is available in the public domain. A comprehensive working draft is expected this year, and the entire sequence is projected to be finished in 2003. DNA sequencing is carried out on mapped, overlapping bacterial clones of 150-200 kb. The working draft comprises assembled unfinished sequence and is released immediately in the public domain. The draft sequence of each clone is then completed, by closing any remaining gaps and resolving any ambiguities, before the entire sequence is checked, annotated, and submitted to the public databases. The sequence of each clone is finished to an accuracy of >99.99%. The availability of a reference sequence of the genome provides the basis for studying the nature of sequence variation, particularly single nucleotide polymorphisms (SNPs), in human populations. SNP typing is a powerful tool for genetic analysis, and will enable us to uncover the association of loci at specific sites in the genome with many disease traits. SNPs occur at a frequency of approximately 1 SNP/kb throughout the genome when the sequence of any two individuals is compared. Programs to detect and map SNPs in the human genome are underway with the aim of establishing a SNP map of the genome during the next two years. The human genome sequence will provide a complete description of all the genes. Annotation of the sequence with the gene structures is achieved by a combination of computational analysis (predictive and homology-based) and experimental confirmation by cDNA sequencing. Detecting homologies between newly defined gene products and proteins of known function helps to postulate biochemical functions for them, which can then be tested. Establishing the association of specific genes with disease phenotypes by mutation screening, particularly for monogenic disorders, provides further assistance in defining the functions of some gene products, as well as helping to establish the cause of the disease. As our knowledge of gene sequences and sequence variation in populations increases, we will pinpoint more and more of the genes and proteins that are important in common, complex diseases. A more detailed understanding of the function of the human genome will be achieved as we identify sequences that control gene expression. Given the availability of gene sequences, the expression status of genes in particular tissues can be monitored in parallel. By comparing corresponding genomic sequences in different species (for example: man, mouse, chicken, and zebrafish), regions that have been highly conserved during evolution can be identified, many of which reflect conserved functions such as gene regulation. These approaches promise to greatly accelerate our interpretation of the human genome sequence.

Human Genome Project↗

Functional and structural organization of chlorophyll in the developing photosynthetic membranes of Euglena gracilis Z. II. Formation of system II photosynthetic units during greening under optimal light intensity.

The relationships between light-harvesting chlorophyll and reaction centers in Photosystem II were analyzed during the chloroplast development of dark-grown, non-dividing Euglena gracilis Z. Comparative measurements included light saturation of photosynthesis, oxygen evolution under flashing-light and fluorescence induction. The results obtained can be summarized as follows: (1) Photosystem II photocenters are formed in parallel with chlorophyll synthesis, but after a long lag phase. (2) As a consequence, the chlorophyll reaction center ratio (Emerson's type photosynthetic unit) decreases during greening. (3) This decrease is accompanied by considerable changes in the energy transfer and trapping properties of Photosystem II. Most of the initially synthesized chlorophylls are inactive in the transfer of excitations to active photochemical centers and are shared among newly formed Photosystem II photocenters; as a consequence, the number of chlorophylls functionally connected to each Photosystem II photocenter decreases and cooperatively between these centers appears. Results are discussed in terms of chlorophyll organization in developing photosynthetic membranes with reference to the lake or puddle models of photosynthetic unit organization.

Chlorophyll↗