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PubMed2007

Understanding the recent evolution of the human genome: insights from human-chimpanzee genome comparisons.

The sequencing of the chimpanzee genome and the comparison with its human counterpart have begun to reveal the spectrum of genetic changes that has accompanied human evolution. In addition to gross karyotypic rearrangements such as the fusion that formed human chromosome 2 and the human-specific pericentric inversions of chromosomes 1 and 18, there is considerable submicroscopic structural variation involving deletions, duplications, and inversions. Lineage-specific segmental duplications, detected by array comparative genomic hybridization and direct sequence comparison, have made a very significant contribution to this structural divergence, which is at least three-fold greater than that due to nucleotide substitutions. Since structural genomic changes may have given rise to irreversible functional differences between the diverging species, their detailed analysis could help to identify the biological processes that have accompanied speciation. To this end, interspecies comparisons have revealed numerous human-specific gains and losses of genes as well as changes in gene expression. The very considerable structural diversity (polymorphism) evident within both lineages has, however, hampered the analysis of the structural divergence between the human and chimpanzee genomes. The concomitant evaluation of genetic divergence and diversity at the nucleotide level has nevertheless served to identify many genes that have evolved under positive selection and may thus have been involved in the development of human lineage-specific traits. Genes that display signs of weak negative selection have also been identified and could represent candidate loci for complex genomic disorders. Here, we review recent progress in comparing the human and chimpanzee genomes and discuss how the differences detected have improved our understanding of the evolution of the human genome.

Animals↗
PubMed1988

Inhibition of cell movement and associated changes by hexachlorocyclohexanes due to unregulated intracellular calcium increases.

Hexachlorocyclohexanes (HCCHs) are potent stimulators of polymorphonuclear leukocyte (PMN) oxidative metabolism and of mobilization of calcium from intracellular stores. It was of interest, therefore, to evaluate the effect of HCCHs on PMN orientation and chemotaxis and to determine their effectiveness as chemotaxins. Chemotaxis was evaluated using micro-Boyden chambers, f-actin was quantitated by nitrobenzoxadiazole (NBD)-phallacidin fluorescence, and microtubules were quantitated by observing the concanavalin A (Con A) capping phenomenon. We also evaluated changes in intracellular calcium [Ca2+]i using quin 2 fluorescence. We found that the HCCH isomers were not chemotaxins and that the HCCH isomers that stimulated O2- formation (delta and gamma HCCH) inhibited chemotaxis. This effect was associated with inhibition of orientation. In addition, we found extensive inhibition of both f-actin and Con A cap formation. These effects of HCCH on cell function were associated with marked increases of [Ca2+]i. This work suggests that non-receptor-mediated increases of [Ca2+]i associated with HCCH have divergent effects on cell function and suggests that physiologic responses of PMNs requiring cytoskeletal alterations, such as chemotaxis, depend on the controlled responses of receptor-mediated stimulation.

Actins↗
PubMed2026

Characteristics and assembly mechanisms of tobacco-associated bacteria in typical tobacco-planting regions across China.

INTRODUCTION: Plant-associated microbiota critically modulates host growth and environmental adaptation, yet assembly mechanisms, niche differentiation, and ecological strategies of bacterial communities inhabiting tobacco microhabitats remain poorly elucidated across geographical gradients. METHODS: Here, we systematically characterized bacterial microbiome assembly across five tobacco-associated niches (bulk soil, rhizosphere soil, root, stem, and leaf) from seven typical tobacco-planting regions using 16S rRNA amplicon sequencing, genome annotation, and niche breadth analysis. The independent and interactive effects of geographical location and host compartment on community structure, and further compared genomic traits, functional profiles, and life-history strategies between specialist and generalist bacterial populations were quantified. RESULTS: The results revealed a deterministic soil-plant continuum stratification of bacterial communities and diversity, with progressively simplified communities and decreasing alpha diversity from bulk soil to above-ground tissues, accompanied by progressive dominance of Proteobacteria. Geographical factors predominantly structured soil microbial communities via divergent edaphic properties, while host filtering acted as a universal dominant driver shaping endophytic microbiome assembly. Niche differentiation analysis demonstrated that niche-specialized bacterial ASVs overwhelmingly dominated all microhabitats and geographical sites, whereas generalist taxa only constituted auxiliary populations. Although specialist and generalist microbes exhibited highly conserved core genomic architectures and overall functional repertoires, they displayed distinct niche-specific functional divergence in metabolic pathways, stress resistance, and secondary metabolism across host compartments. Life-history strategy analysis further revealed that Y-strategist represented the core adaptive bacterial population, especially enriched in above-ground tobacco tissues. DISCUSSION: Our study establishes a hierarchical dual-filtering assembly model for tobacco microbiota, clarifies the ecological differentiation and functional adaptation of specialist and generalist bacteria, and provides fundamental insights into the assembly rules and adaptive mechanisms of crop-associated microbiomes for future microbial resource utilization and agricultural microbiome regulation.

biogeography↗
PubMed1992

Isolation and characterization of a highly divergent HIV-2[GH-2]: generation of an infectious molecular clone and functional analysis of its rev-responsive element in response to primate retrovirus transactivators (Rev and Rex).

A highly divergent HIV-2 designated as HIV-2[GH-2] was obtained from an AIDS-related complex (ARC) patient in Ghana. A full-length molecular clone of this isolate was obtained and a biologically active clone was constructed. Its restriction pattern differed from that of prototype HIV-2[GH-1] in 25 of 35 restriction sites, but was strikingly similar to a previously characterized HIV-2 isolate from a Ghanaian (HIV-2ALT). The conserved integrase region (288-bp fragment) previously displayed 95% identity with that of ALT but 17-20% divergence from the HIV-2 prototype member, and a new distinct subgroup (HIV-2b) of HIV-2 consisting of GH-2 and ALT was postulated (Miura et al. 1991.) These isolates, however, were biologically distinguishable from each other by its replication capacity in a monocyte line, U937, in which GH-2 could not grow but ALT grew well. In addition, the nucleotide sequence of the LTR of this new isolate displays 21% divergence from that of prototype HIV-2[GH-1], but the core enhancer, Sp1 binding sites and TATA box were conserved. Although the 3' half of the env gene sequence which is deleted in HIV-2ALT clone showed 27% diversity from the prototype, functional differences in the rev-responsive element were not observed.

Cloning, Molecular↗
PubMed2000

The role of hydrophobicity patterns in prion folding as revealed by recurrence quantification analysis of primary structure.

It has been suggested that the number and strength of local contacts are the major factors governing conformation accessibility of model two ground-state polypeptide chains. This phenomenology has been posed as a possible factor influencing prion folding. To test this conjecture, recurrence quantification analysis was applied to two model 36mers, and the Syrian hamster prion protein. A unique divergence of the radius function for the recurrence quantification variable %DET of hydrophobicity patterns was observed for both 36mers, and in a critical region of the hamster prion protein. This divergence suggests a partition between strong short- and long-range hydrophobicity patterns, and may be an important factor in prion phenomenology, along with other global thermodynamic factors.

Algorithms↗
PubMed2002

RIO: analyzing proteomes by automated phylogenomics using resampled inference of orthologs.

BACKGROUND: When analyzing protein sequences using sequence similarity searches, orthologous sequences (that diverged by speciation) are more reliable predictors of a new protein's function than paralogous sequences (that diverged by gene duplication). The utility of phylogenetic information in high-throughput genome annotation ("phylogenomics") is widely recognized, but existing approaches are either manual or not explicitly based on phylogenetic trees. RESULTS: Here we present RIO (Resampled Inference of Orthologs), a procedure for automated phylogenomics using explicit phylogenetic inference. RIO analyses are performed over bootstrap resampled phylogenetic trees to estimate the reliability of orthology assignments. We also introduce supplementary concepts that are helpful for functional inference. RIO has been implemented as Perl pipeline connecting several C and Java programs. It is available at http://www.genetics.wustl.edu/eddy/forester/. A web server is at http://www.rio.wustl.edu/. RIO was tested on the Arabidopsis thaliana and Caenorhabditis elegans proteomes. CONCLUSION: The RIO procedure is particularly useful for the automated detection of first representatives of novel protein subfamilies. We also describe how some orthologies can be misleading for functional inference.

Animals↗
PubMed1998

Functional conservation of the transportin nuclear import pathway in divergent organisms.

Human transportin1 (hTRN1) is the nuclear import receptor for a group of pre-mRNA/mRNA-binding proteins (heterogeneous nuclear ribonucleoproteins [hnRNP]) represented by hnRNP A1, which shuttle continuously between the nucleus and the cytoplasm. hTRN1 interacts with the M9 region of hnRNP A1, a 38-amino-acid domain rich in Gly, Ser, and Asn, and mediates the nuclear import of M9-bearing proteins in vitro. Saccharomyces cerevisiae transportin (yTRN; also known as YBR017c or Kap104p) has been identified and cloned. To understanding the nuclear import mediated by yTRN, we searched with a yeast two-hybrid system for proteins that interact with it. In an exhaustive screen of the S. cerevisiae genome, the most frequently selected open reading frame was the nuclear mRNA-binding protein, Nab2p. We delineated a ca.-50-amino-acid region in Nab2p, termed NAB35, which specifically binds yTRN and is similar to the M9 motif. NAB35 also interacts with hTRN1 and functions as a nuclear localization signal in mammalian cells. Interestingly, yTRN can also mediate the import of NAB35-bearing proteins into mammalian nuclei in vitro. We also report on additional substrates for TRN as well as sequences of Drosophila melanogaster, Xenopus laevis, and Schizosaccharomyces pombe TRNs. Together, these findings demonstrate that both the M9 signal and the nuclear import machinery utilized by the transportin pathway are conserved in evolution.

Amino Acid Sequence↗
PubMed1977

Intestinal function and morphology in strongyloidiasis.

Divergent available information on the capability of Strongyloides stercoralis to cause malabsorption prompted a long-term observation in which the nutritional state of the subjects was carefully defined. In spite of moderate to severe symptoms, well nourished patients, even with segmental jejunitis, did not show malabsorption. All patients presenting this parasitic infection with concomitant malnutrition showed absorptive defects. Abnormal absorption persisted in spite of parasitic cure when malnutrition was not immediately corrected, and disappeared with correction of the malnutrition even if parasitic infection was allowed to continue. The present experience indicates that the malabsorption syndrome seen in some cases of S. stercoralis infection is secondary to the concomitant malnutrition and not to the parasite per se.

Duodenum↗
PubMed1987

The human myc gene family: structure and activity of L-myc and an L-myc pseudogene.

We have determined the nucleotide sequence and transforming activity of the human L-myc gene and a processed L-myc pseudogene (L-myc psi). We demonstrate by cotransformation assays that a 10.6-kb EcoRI fragment derived from a human placental library contains a complete and functional L-myc gene including transcriptional regulatory sequences sufficient for expression in rat embryo fibroblasts. Organization of the L-myc gene was determined by comparing its sequence to those of the L-myc psi gene and an L-myc cDNA clone derived from a human small cell lung carcinoma. Our results show that L-myc has a three-exon organization similar to that of the c-myc and N-myc genes. The putative L-myc gene product consists of 364 amino acids and contains five of the seven homology regions highly conserved between c-myc and N-myc. These conserved regions are located along the entire length of the putative L-myc protein and are interspersed among nonconserved regions. While the putative L-myc gene product is of a smaller size when compared to the c- and N-myc proteins, the relative positions of certain conserved residues occur in corresponding locations along the peptide backbone of the three proteins. In addition, comparison of the human and murine L-myc gene sequences indicate that the relatively large 5' and 3' untranslated regions are evolutionarily conserved, but that these sequences are totally divergent between the L-, c-, and N-myc genes. Finally, we demonstrate that, like the N- and c-myc genes, the L-myc gene can cooperate with a mutant Ha-ras gene to cause malignant transformation of rat embryo fibroblasts in culture. Our analyses clearly prove that L-myc represents a functional member of the myc oncogene family and further delineate structural features that may be important for the common and divergent functions of the members of this gene family.

Amino Acid Sequence↗
PubMed1994

Axon branching of medullary expiratory neurons in the lumbar and the sacral spinal cord of the cat.

Intraspinal axon collaterals of expiratory (E) neurons in the caudal nucleus retroambigualis extending their desending spinal axons to the lower lumbar (L6-L7) and the sacral (S1-S3) segments were investigated in anesthetized cats. To search for axon collaterals of single E neurons in the lumbar segments, the spinal gray matter was microstimulated from the dorsal to the ventral sites at 100 microns intervals with an intensity of 150-250 microA at 1 mm intervals rostrocaudally along the spinal cord, and effective stimulating sites of antidromic activation in axon collaterals were systematically mapped. In addition, the detailed trajectory of collaterals in the upper lumbar (L1-L3), the middle lumbar (L4-L5), and the sacral (S1-S3) spinal cord was examined by microstimulation at a matrix of points 100-200 microns apart with a maximum stimulus intensity of 50 microA. The trajectory of axon collaterals was reconstructed on the basis of the location of low-threshold foci and the latency of antidromic spikes. Virtually all E neurons examined had 1-7 collaterals at widely separated segments of the lumbar cord. Many axon collaterals were found in the upper lumbar spinal cord as compared to the middle and the lower lumbar spinal cord. The locations of axon collaterals in the upper lumbar spinal cord overlapped with those of abdominal motoneurons. Axon collaterals in the sacral gray matter were found in 3 of 9 E neurons. Axon collaterals were found within the nucleus of Onuf, in the region dorsal to the nucleus of Onuf, and in the intermediate region. The functional significance of the divergent distribution of multiple axon collaterals of single E neurons in different spinal levels of the lumbar and the sacral spinal cord is discussed in relation to the respiratory function of E neurons and other spinal motor activities.

Animals↗
PubMed2003

Birth-and-death evolution in primate MHC class I genes: divergence time estimates.

The major histocompatibility complex (MHC) is a multigene family that mediates the host immune response by helping T lymphocytes to recognize and respond to foreign antigens. The high degree of polymorphism and a quick turnover of the genetic loci make the evolution of MHC genes an intriguing subject of study. To understand the evolutionary pattern of this multigene family, we studied the phylogeny and divergence times of six functional MHC class I loci from primate species. On the phylogenetic trees, locus F occupies the most basal position among these loci. Our results suggest that the F locus diverged from the other MHC class I loci about 46-66 MYA. The major diversification of the other class I loci was estimated to have occurred at about 35-49 MYA, which is before the time of separation of Old World-New World monkeys. The gene duplication leading to the classical C locus in great apes appears to have occurred about 21-28 MYA. At approximately the same time the duplication of the B locus occurred in macaques. The oldest allelic lineages of A, B, and C loci in humans seem to have appeared at least 14-19, 10-15, and 13-17 MYA, respectively. Our phylogenetic analysis supports the hypothesis that the nonclassical locus F has diverged from the rest of class I loci very early in primate evolution. The overall phylogenetic pattern observed among class I genes is consistent with the model of birth-and-death evolution.

Animals↗
PubMed1994

Evolution of distinct developmental functions of three Drosophila genes by acquisition of different cis-regulatory regions.

It is generally accepted that the specific function of a gene depends on its coding sequence. The three paired-box and homeobox genes paired (prd), gooseberry (gsb) and gooseberry neuro (gsbn) have distinct developmental functions in Drosophila embryogenesis. During the syncytial blastoderm stage, the pair-rule gene prd activates segment-polarity genes, such as gsb, wingless (wg), and engrailed (en), in segmentally repeated stripes. After germ-band extension, gsb maintains the expression of wg, which in turn specifies the denticle pattern by repressing a default state of ubiquitous denticle formation in the ventral epidermis. In addition, gsb activates gsbn, which is expressed mainly in the central nervous system, suggesting that gsbn is involved in neural development. Here we show that, despite the functional difference and the considerably diverged coding sequence of these genes, their proteins have conserved the same function. The finding that the essential difference between genes may reside in their cis-regulatory regions exemplifies an important evolutionary mechanism of how function diversifies after gene duplication.

Animals↗
PubMed2001

Identification of homology in protein structure classification.

Structural biology and structural genomics are expected to produce many three-dimensional protein structures in the near future. Each new structure raises questions about its function and evolution. Correct functional and evolutionary classification of a new structure is difficult for distantly related proteins and error-prone using simple statistical scores based on sequence or structure similarity. Here we present an accurate numerical method for the identification of evolutionary relationships (homology). The method is based on the principle that natural selection maintains structural and functional continuity within a diverging protein family. The problem of different rates of structural divergence between different families is solved by first using structural similarities to produce a global map of folds in protein space and then further subdividing fold neighborhoods into superfamilies based on functional similarities. In a validation test against a classification by human experts (SCOP), 77% of homologous pairs were identified with 92% reliability. The method is fully automated, allowing fast, self-consistent and complete classification of large numbers of protein structures. In particular, the discrimination between analogy and homology of close structural neighbors will lead to functional predictions while avoiding overprediction.

Automation↗
PubMed1993

Multiple regions of a divergent promoter control the expression of the Agrobacterium rhizogenes aux1 and aux2 plant oncogenes.

The two auxin biosynthesis genes, aux1 and aux2 of Agrobacterium rhizogenes strain A4, are located on opposite DNA strands with a short integenic region (394 bp) between their coding sequences. A functional analysis of this divergent promoter is presented. The transcription initiation sites of the two aux genes were determined and regions important for promoter activity were identified by deletion and transient expression analyses in tobacco protoplasts. The promoter activity of the aux intergenic region was demonstrated. A strong enhancer element contained within an 84 bp promoter fragment was identified. Far upstream regions were shown to have negative effects on the promoter activity of the short intergenic region. Interactions between positive elements in the intergenic region and negative effects of the upstream sequences may be the basis of strict control of the auxin biosynthesis necessary for the induction and maintenance of hairy root growth.

Base Sequence↗
PubMed1999

Three structurally and functionally conserved Hlx genes in zebrafish.

For the Hlx class, which includes homeodomains (HD) that are similar to Drosophila H2.0, few members have been identified in vertebrates. In this report, we describe three zebrafish genes, hlx1, hlx2 and hlx3, related to the murine Dbx genes. The proteins encoded by hlx1 and hlx2 have about the same sequence identity to Dbx1 (approximately 60%), suggesting that they derive from a duplication in the fish lineage. This is supported by similarities in the embryonic expression patterns and promoter sequence conservation. The zebrafish Hlx3 protein is related to murine Dbx2, but it is apparently too diverged to be orthologous. Our phylogenetic analysis of all the known HD sequences of the Hlx class also shows that it can be divided into at least two distinct families. All the Dbx-like genes have similar expression in the embryonic nervous system. However, the initial expression patterns of the zebrafish hlx genes are quite unique, suggesting that some functional divergence has occurred between fish and mammals.

Amino Acid Sequence↗
PubMed1987

Poststenotic flow velocity changes as a function of stenosis geometry.

We used an in vitro pulsatile flow model to examine the velocity profile distal to a variable nonaxisymmetric stenosis. Using a continuous-wave Doppler velocimeter, the peak systolic frequency was determined distal to the stenosis and in planes parallel and perpendicular to the long axis of the stenosis. In both planes, an exponential regression best describes the relationship between peak systolic frequency and reduction in cross-sectional area. Regressions at each point of insonation diverged as a direct function of reduction in cross-sectional area and as an indirect function of distance from the stenosis. At each point of insonation, regressions representing the relationship in the mutually perpendicular planes diverged in direct proportion to reduction in cross-sectional area. Slopes were greater in parallel planes of insonation. These data demonstrate that two variables, distance and geometry, may influence the results of spectral analytic studies.

Arterial Occlusive Diseases↗
PubMedDate not supplied

Evolutionary integration and morphological diversification in complex morphological structures: mandible shape divergence in spiny rats (Rodentia, Echimyidae).

The rodent mandible has become a paradigm for studies on the development and evolution of complex morphological structures. We use a combination of geometric and multivariate morphometric methods in order to assess the correspondence between integration patterns and a priori biological models in the context of evolutionary shape divergence in the mandible of rodents of the family Echimyidae. The correlation of shape distances among operational taxonomic units (individuals, species, genera) in separate morphogenetic components allowed the construction of integration matrices among mandible components for data sets corresponding to varying levels of genetic divergence (intergeneric, interspecific, and intrapopulational). The integration matrices were associated with a priori biological (developmental, genetical, modular) models, and the maximum integration axes (singular warps) were compared with realized axes of maximum interspecific variation (relative warps). The integration pattern and intensity were not stable in data sets with different levels of genetic divergence, and the varying functional demands during the ecological radiation in the family were probably responsible for the differences in observed integration patterns. Developmental and genetic models were significantly associated with the interspecific integration patterns observed, suggesting a role for neutral evolution during the evolutionary divergence of mandible shape. However, directional and stabilizing selection were not discarded as processes responsible for the generation of interspecific integration. The choreography of the morphogenetic components in the mandible is highly flexible and the integrated groups of components can be reorganized depending on functional demands during evolutionary shape changes.

Animals↗
PubMed2006

Variation within and among species in gene expression: raw material for evolution.

Heritable variation in regulatory or coding regions is the raw material for evolutionary processes. The advent of microarrays has recently promoted examination of the extent of variation in gene expression within and among taxa and examination of the evolutionary processes affecting variation. This review examines these issues. We find: (i) microarray-based measures of gene expression are precise given appropriate experimental design; (ii) there is large inter-individual variation, which is composed of a minor nongenetic component and a large heritable component; (iii) variation among populations and species appears to be affected primarily by neutral drift and stabilizing selection, and to a lesser degree by directional selection; and (iv) neutral evolutionary divergence in gene expression becomes nonlinear with greater divergence times due to functional constraint. Evolutionary analyses of gene expression reviewed here provide unique insights into partitioning of regulatory variation in nature. However, common limitations of these studies include the tendency to assume a linear relationship between expression divergence and species divergence, and failure to test explicit hypotheses that involve the ecological context of evolutionary divergence.

Animals↗