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Results for “evolutionary analysis”

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PubMed2000

Expansion and molecular evolution of the interferon-induced 2'-5' oligoadenylate synthetase gene family.

The mammalian 2'-5' oligoadenylate synthetases (2'-5'OASs) are enzymes that are crucial in the interferon-induced antiviral response. They catalyze the polymerization of ATP into 2'-5'-linked oligoadenylates which activate a constitutively expressed latent endonuclease, RNaseL, to block viral replication at the level of mRNA degradation. A molecular evolutionary analysis of available OAS sequences suggests that the vertebrate genes are members of a multigene family with its roots in the early history of tetrapods. The modern mammalian 2'-5'OAS genes underwent successive gene duplication events resulting in three size classes of enzymes, containing one, two, or three homologous domains. Expansion of the OAS gene family occurred by whole-gene duplications to increase gene content and by domain couplings to produce the multidomain genes. Evolutionary analyses show that the 2'-5'OAS genes in rodents underwent gene duplications as recently as 11 MYA and predict the existence of additional undiscovered OAS genes in mammals.

2',5'-Oligoadenylate Synthetase↗

PubMed2003

Differential expansion of zinc-finger transcription factor loci in homologous human and mouse gene clusters.

Mammalian genomes carry hundreds of Krüppel-type zinc finger (ZNF) genes, most of which reside in familial clusters. ZNF genes encoding Krüppel-associated box (KRAB) motifs are especially prone to this type of tandem organization. Despite their prevalence, little is known about the functions or evolutionary histories of these clustered gene families. Here we describe a homologous pair of human and mouse KRAB-ZNF gene clusters containing 21 human and 10 mouse genes, respectively. Evolutionary analysis uncovered only three pairs of putative orthologs and two cases where a single gene in one species is related to multiple genes in the other; several human genes have no obvious homolog in mouse. We deduce that duplication and loss of ancestral cluster members occurred independently in the primate and rodent lineages after divergence, yielding substantially different ZNF gene repertoires in humans and mice. Differences in expression patterns and sequence divergence within the DNA binding regions of predicted proteins suggest that the duplicated genes have acquired novel functions over evolutionary time. Since KRAB-ZNF proteins are predicted to function as transcriptional regulators, the elaboration of new lineage-specific genes in this and other clustered ZNF families is likely to have had a significant impact on species-specific aspects of biology.

Amino Acid Sequence↗

PubMed1995

A novel measure of genetic distance for highly polymorphic tandem repeat loci.

Genetic distance measures are indicators of relatedness among populations or species and are useful for reconstructing the historic and phylogenetic relationships among such groups. Classical measures of genetic distance were developed to analyze biochemical and serological polymorphisms, systems which generally show limited variability. However, these traditional measures of genetic distance are inadequate for the analysis of certain classes of variable number tandem repeat (VNTR) loci, which have a larger number of alleles and higher levels of heterozygosity than traditional genetic markers. At the higher levels of heterozygosity observed at these loci, the standard measures of genetic distance are nonlinear and do not account for the mutational mechanisms of hypervariable loci. We have developed a measure of genetic distance, DSW, which is appropriate for the analysis of highly polymorphic DNA loci. Using computer simulations of diverging populations, we show that DSW conforms to linearity and that the variance is similar in magnitude to traditional measures of genetic distance. Comparisons of phylogenetic trees derived from the simulated divergence of human racial groups demonstrate that the branch lengths of trees prepared using DSW are more similar to the model tree than those generated using other measures. Finally, we demonstrate the applicability of DSW to evolutionary analysis by reconstructing the relationships among eight human populations using 14 microsatellite and STR loci. The phylogenetic trees generated using DSW are different from trees constructed with traditional measures and better reflect the well-documented ancient divergence of African and non-African populations.

Animals↗

PubMed1996

The evolution of angiosperm seed proteins: a methionine-rich legumin subfamily present in lower angiosperm clades.

Analysis of legumin-encoding cDNAs from Dioscorea caucasica Lipsky (Dioscoreaceae) and from Asarum europaeum L. (Aristolochiaceae) shows that there is an especially methionine-rich legumin subfamily present in the lower angiosperm clades including the Monocotyledoneae. It is characterized by a methionine content of 3-4 mol% which is roughly triple the methionine proportion of most other legumins. These "MetR" legumins, if present, still have to be detected in the higher angiosperms including the important seed crops. Evolutionary analysis suggests that the MetR legumins are the result of a gene duplication allowing the differentiation of legumin genes according to their sulfur content. The duplication event must have taken place before the split into mono- and dicotyledonous plants but probably after the separation of angiosperms and gymnosperms.

Amino Acid Sequence↗

PubMed2001

On the origin of self-incompatibility haplotypes: transition through self-compatible intermediates.

Self-incompatibility (SI) in flowering plants entails the inhibition of fertilization by pollen that express specificities in common with the pistil. In species of the Solanaceae, Rosaceae, and Scrophulariaceae, the inhibiting factor is an extracellular ribonuclease (S-RNase) secreted by stylar tissue. A distinct but as yet unknown gene (provisionally called pollen-S) appears to determine the specific S-RNase from which a pollen tube accepts inhibition. The S-RNase gene and pollen-S segregate with the classically defined S-locus. The origin of a new specificity appears to require, at minimum, mutations in both genes. We explore the conditions under which new specificities may arise from an intermediate state of loss of self-recognition. Our evolutionary analysis of mutations that affect either pistil or pollen specificity indicates that natural selection favors mutations in pollen-S that reduce the set of pistils from which the pollen accepts inhibition and disfavors mutations in the S-RNase gene that cause the nonreciprocal acceptance of pollen specificities. We describe the range of parameters (rate of receipt of self-pollen and relative viability of inbred offspring) that permits the generation of a succession of new specificities. This evolutionary pathway begins with the partial breakdown of SI upon the appearance of a mutation in pollen-S that frees pollen from inhibition by any S-RNase presently in the population and ends with the restoration of SI by a mutation in the S-RNase gene that enables pistils to reject the new pollen type.

Evolution, Molecular↗

PubMed1994

Genetic, molecular and developmental analysis of the glutamine synthetase isozymes of Drosophila melanogaster.

The glutamine synthetase isozymes of Drosophila melanogaster offer an attractive model for the study of the molecular genetics and evolution of a small gene family encoding enzymatic isoforms that evolved to assume a variety of specific and sometimes essential biological functions. In Drosophila melanogaster two GS isozymes have been described which exhibit different cellular localisation and are coded by a two-member gene family. The mitochondrial GS structural gene resides at the 21B region of the second chromosome, the structural gene for the cytosolic isoform at the 10B region of the X chromosome. cDNA clones corresponding to the two genes have been isolated and sequenced. Evolutionary analysis data are in accord with the hypothesis that the two Drosophila glutamine synthetase genes are derived from a duplication event that occurred near the time of divergence between Insecta and Vertebrata. Both isoforms catalyse all reactions catalysed by other glutamine synthetases, but the different kinetic parameters and the different cellular compartmentalisation suggest strong functional specialisation. In fact, mutations of the mitochondrial GS gene produce embryo-lethal female sterility, defining a function of the gene product essential for the early stages of embryonic development. Preliminary results show strikingly distinct spatial and temporal patterns of expression of the two isoforms at later stages of development.

Animals↗

PubMed2025

Comparison of phylogenetic metrics of transmission in symptomatic and asymptomatic tuberculosis.

BACKGROUND: Understanding drivers of Mycobacterium tuberculosis (Mtb) transmission remains a critical challenge in high-burden settings. Tuberculosis control efforts traditionally target symptomatic individuals, yet the role of asymptomatic cases in sustaining transmission is increasing recognized. METHODS: We conducted a genomic and epidemiological analysis of Mtb isolates collected in Mato Grosso do Sul, Brazil, between 2008 and 2024. From 2017 to 2022, active case finding was performed in three of the state's largest prisons, whereby sputum was collected from individuals irrespective of symptoms and tested by GeneXpert and culture. We evaluated several metrics of recent transmission from symptomatic and asymptomatic individuals, including phylogenetic clustering, Time-scaled Haplotype Density (THD), Local Branching Index (LBI), and transmission probabilities inferred using the Bayesian Reconstruction and Evolutionary Analysis of Transmission Histories (BREATH). FINDINGS: We sequenced 2,362 Mtb strains, of which 3.5% (115/2,362) were resistant to at least one drug, and 0.6% (16/2,362) were multi-drug resistant. Most strains were lineage 4, and 78.2% of all isolates were part of a genomic cluster. Among 2,362 individuals with tuberculosis, 1,137 were incarcerated at the time of diagnosis. Among these, 505 were identified through active case finding: 277 had symptomatic disease and 228 had asymptomatic tuberculosis. There was no significant difference in phylogenetic clustering proportion (77% vs. 85%; p= 0.816), THD (median 0.50 vs. 0.39; p = 0.120), or LBI (median 0.00863 vs. 0.00871; p = 0.086) between symptomatic and asymptomatic individuals. Bayesian transmission trees revealed no significant difference in the number of secondary infections inferred from symptomatic compared with asymptomatic individuals (p = 0.56). These findings were consistent across genomic clusters and robust to model assumptions. INTERPRETATION: We identified no differences in transmission from symptomatic compared with asymptomatic individuals, using several genomic measures of transmission, underscoring the substantial contribution that asymptomatic tuberculosis makes to transmission at the population level.

Asymptomatic↗

PubMed2025

Transcriptome-wide analysis reveals sequence selection to avoid mRNA aggregation in E. coli.

The stability of RNA base pairing and its limited four-letter code create an intrinsic potential for promiscuous RNA-RNA interactions. In vitro, such interactions drive RNA to self-assemble into aggregates. This raises a fundamental unanswered question: within a confined cellular volume at physiological mRNA abundances, how much aggregation would arise from sequence-encoded chemistry alone? Here, we establish this baseline with large-scale kinetic simulations of the E. coli transcriptome. Our simulations reveal that sequence-encoded base-pairing energetics is sufficient to generate a dynamic network of large aggregates, organized by long, multivalent mRNA hubs. Strikingly, evolutionary analysis shows that native E. coli sequences exhibit clear signatures of selection to counteract this propensity: they fold more stably, minimize unstructured regions, and form weaker intermolecular contacts than dinucleotide-preserving controls. These findings demonstrate that maintaining transcriptome solubility has been a significant, previously unrecognized constraint shaping genome evolution, and provide a new lens to interpret cellular RNA management.

Biological Sciences (Biophysics and Computational ↗

PubMed1996

Theoretical approaches to the analysis of homeobox gene evolution.

The homeobox gene system presents a unique model for experimental and theoretical analyses of gene evolution. Homeobox genes play a role in patterning the embryonic development of diverse organisms and as such are likely to have been fundamental to the evolution of the specialized body plans of many animal species. The organization of Hox-genes in chromosomal, clusters in many species implicates gene duplication as a prominent mechanism in the evolution of this multigene family. I review here various theoretical analyses that have contributed to our understanding of the molecular evolution of this class of developmental control genes. This article also illustrates relationships between theoretical predictions and experimental studies and outlines future avenues for the evolutionary analysis of developmental systems.

Animals↗

PubMed1994

Comparative analysis of human DNA variations by fluorescence-based sequencing of PCR products.

Automated, direct cycle sequencing of purified double-stranded PCR products using Taq polymerase and fluorescently labeled dideoxynucleotide terminators provides a robust and highly reproducible method for identifying DNA sequence variations in sequence-tagged sites. We describe a simple and sensitive strategy that reliably detects the presence of DNA variations when sequencing traces from several different individuals are compared. We also demonstrate the use of this strategy to estimate allele frequencies of single nucleotide substitutions in a population. Taken together, this approach provides an automated method for conducting rapid population studies of candidate gene regions that are in linkage or association with a specific disease and for comparative evolutionary analysis of selected regions of the human genome.

Alleles↗

PubMed2003

The evolution of enzyme specificity in Fasciola spp.

Fasciola spp., commonly known as liver fluke, are significant trematode parasites of livestock and humans. They secrete several cathepsin L-like cysteine proteases, some of which differ in enzymatic properties and timing of expression in the parasite's life cycle. A detailed sequence and evolutionary analysis is presented, based on 18 cathepsin L-like enzymes isolated from Fasciola spp. (including a novel clone identified in this study). The enzymes form a monophyletic group which has experienced several gene duplication events over the last approximately 135 million years, giving rise to the present-day enzymatic repertoire of the parasite. This timing of these duplications appears to correlate with important points in the evolution of the mammalian hosts. Furthermore, the dates suggest that Fasciola hepatica and Fasciola gigantica diverged around 19 million years ago. A novel analysis, based on the pattern of amino acid diversity, was used to identify sites in the enzyme that are predicted to be subject to positive adaptive evolution. Many of these sites occur within the active site cleft of the enzymes, and hence would be expected to lead to differences in substrate specificity. Using homology modeling, with reference to previously obtained biochemical data, we are able to predict S2 subsite specificity for these enzymes: specifically those that can accommodate bulky hydrophobic residues in the P2 position and those that cannot. A number of other positions subject to evolutionary pressure and potentially significant for enzyme function are also identified, including sites anticipated to diminish cystatin binding affinity.

Amino Acid Sequence↗

PubMed2002

Molecular evolution of H6 influenza viruses from poultry in Southeastern China: prevalence of H6N1 influenza viruses possessing seven A/Hong Kong/156/97 (H5N1)-like genes in poultry.

The A/teal/Hong Kong/W312/97 (H6N1) influenza virus and the human H5N1 and H9N2 influenza viruses possess similar genes encoding internal proteins, suggesting that H6N1 viruses could become novel human pathogens. The molecular epidemiology and evolution of H6 influenza viruses were characterized by antigenic and genetic analyses of 29 H6 influenza viruses isolated from 1975 to 1981 and 1997 to 2000. Two distinct groups were identified on the basis of their antigenic characteristics. Phylogenetic analysis revealed that all H6N1 viruses isolated from terrestrial poultry in 1999 and 2000 are closely related to A/teal/Hong Kong/W312/97 (H6N1), and the nucleotide sequences of these viruses and of A/Hong Kong/156/97 (H5N1) were more than 96% homologous. The hemagglutinin (HA) of the 1999 and 2000 terrestrial viruses does not have multiple basic amino acids at the site of cleavage of HA1 to HA2; however, a unique insertion of aspartic acid in HA1 between positions 144 and 145 (H3 numbering) was found. The neuraminidase of these terrestrial H6N1 viruses has a deletion of 19 amino acids characteristic of A/Hong Kong/156/97 (H5N1). Evolutionary analysis suggested that these H6N1 viruses coevolved with A/quail/Hong Kong/G1/97-like H9N2 viruses and became more adapted to terrestrial poultry. These terrestrial 1999 and 2000 A/teal/Hong Kong/W312/97 (H6N1)-like viruses, along with the H9N2 viruses, could have been involved in the genesis of the pathogenic H5N1 influenza viruses of 1997. The presence of H6N1 viruses in poultry markets in Hong Kong that possess seven of the eight genes of the A/Hong Kong/156/97 (H5N1) virus raises the following fundamental questions relevant to influenza pandemic preparedness: could the pathogenic H5N1 virus reemerge and could the H6N1 viruses directly cross the species barrier to mammals?

Animals↗

PubMedDate not supplied

Cloning and sequence analysis of kappa and gamma cynomolgus monkey immunoglobulin cDNAs.

One gamma heavy chain and 10 kappa light chain cynomolgus monkey (Macaca fascicularis) immunoglobulin cDNAs have been cloned and sequenced. Comparisons of the variable (V) regions to human antibody sequences have revealed extensive identity, exhibiting 93% at the amino acid level for the VH framework regions, and 88-99% for the V kappa frameworks. Identification of very few cynomolgus monkey-specific framework region residues suggests a role for cynomolgus monkey antibodies as donators of variable regions to chimeric monoclonal antibodies for utilisation in human therapy with human constant (C) regions. The cynomolgus monkey C kappa region exhibited 83% amino acid identity to its human counterpart, and the C gamma region was 95, 93, 95, and 95% similar to the human C gamma 1, C gamma 2, C gamma 3, and C gamma 4 regions, respectively. Evolutionary analysis of the C gamma genes, using the silent molecular clock, suggests that the divergence between cynomolgus monkey and human occurred before the time at which the ancestral gamma gene diverged into the multiple isotypes observed in humans.

Amino Acid Sequence↗

PubMed1995

Identification and molecular evolution of new dynein-like protein sequences in rat brain.

RT-PCR cloning was performed to find unknown members of the dynein superfamily expressed in rat brain. Six kinds of degenerate primers designed for the dynein catalytic domain consensuses were used for extensive PCR amplifications. We have sequenced 550 plasmid clones which turned out to include 13 kinds of new dynein-like sequences (DLP1-8, 9A/B, 10-12) and cytoplasmic dynein heavy chain. In these clones, alternative splicing was detected for a 105 nt-domain containing the CFDEFNRI consensus just downstream of the most N-terminal P-loop (DLP9A and 9B). By using these obtained sequences, initial hybridization studies were performed. Genomic Southern blotting showed each sequence corresponds to a single copy of the gene, while northern blotting of adult brain presented more than one band for some subtypes. We further accomplished molecular evolutionary analysis to recognize their phylogenetic origins for the axonemal and non-axonemal (cytoplasmic) functions. Different methods (UPGMA, NJ and MP) presented well coincident phylogenetic trees from 44 partial amino acid sequences of dynein heavy chain from various eukaryotes. The trunk for all the cytoplasmic dynein heavy chain homologues diverged directly from the root of the phylogenetic tree, suggesting that the first dynein gene duplication defined two distinct functions as respective subfamilies. Of particular interest, we found a duplication event of the cytoplasmic dynein heavy chain gene giving rise to another subtype, DLP4, located between the divergence of yeast and that of Dictyostelium. Such evolutionary topology builds up an inceptive hypothesis that there are at least two non-axonemal dynein heavy chains in mammals.

Amino Acid Sequence↗

PubMed2001

The human ATP-binding cassette (ABC) transporter superfamily.

The ATP-binding cassette (ABC) transporter superfamily contains membrane proteins that translocate a variety of substrates across extra- and intra-cellular membranes. Genetic variation in these genes is the cause of or contributor to a wide variety of human disorders with Mendelian and complex inheritance, including cystic fibrosis, neurological disease, retinal degeneration, cholesterol and bile transport defects, anemia, and drug response. Conservation of the ATP-binding domains of these genes has allowed the identification of new members of the superfamily based on nucleotide and protein sequence homology. Phylogenetic analysis is used to divide all 48 known ABC transporters into seven distinct subfamilies of proteins. For each gene, the precise map location on human chromosomes, expression data, and localization within the superfamily has been determined. These data allow predictions to be made as to potential functions or disease phenotypes associated with each protein. In this paper, we review the current state of knowledge on all human ABC genes in inherited disease and drug resistance. In addition, the availability of the complete Drosophila genome sequence allows the comparison of the known human ABC genes with those in the fly genome. The combined data enable an evolutionary analysis of the superfamily. Complete characterization of all ABC from the human genome and from model organisms will lead to important insights into the physiology and the molecular basis of many human disorders.

ATP-Binding Cassette Transporters↗

PubMed1997

Evolutionary diversity of symbiotically induced nodule MADS box genes: characterization of nmhC5, a member of a novel subfamily.

Unique organs called nodules form on legume roots in response to intracellular infection by soil bacteria in the genus Rhizobium. This study describes a new MADS box gene, nmhC5, which along with nmh7 (J. Heard and K. Dunn, Proc. Natl. Acad. Sci. USA 92:5273-5277, 1995), is expressed in alfalfa (Medicago sativa) root nodules. Together, these genes represent the first putative transcription factors identified in nodules. Expression in a root-derived structure supports the growing sentiment that MADS box proteins have diverse roles in plant development. Comparison of the putative translation product of nmhC5 with those of other reported members of the MADS box family suggests that the overall structure of nmhC5 is conserved. Evolutionary analysis among the MADS box family showed that nmhC5 is orthologous to a root-expressed clone in Arabidopsis thaliana, agl17, and that nmh7 is similar to the floral subfamily with AP3 (DefA)/PI (Glo). Consistent with a prediction of homodimer formation, NMHC5 was shown to bind a CArG consensus sequence in vitro. In contrast, NMH7, which shows structural similarity to MADS box proteins that form heterodimers, did not bind the CArG element in an in vitro DNA-binding assay, suggesting the existence of an unknown dimer partner. The root-derived MADS box genes constitute a novel subfamily of vegetatively expressed MADS box genes. The evolutionary diversity between nmh7 and nmhC5 could represent an overall mechanistic conservation between plant developmental processes or could mean that nmh7 and nmhC5 make fundamentally different contributions to the development of the nodule.

Amino Acid Sequence↗

PubMed1997

Entamoeba histolytica contains a gene encoding a homologue to the 54 kDa subunit of the signal recognition particle.

We have determined the nucleotide sequence and predicted amino acid sequence of the 54 kDa subunit of the signal recognition particle (SRP54) from the amitochondrial protist Entamoeba histolytica. The SRP54 gene was isolated from a genomic library using a polymerase chain reaction (PCR) probe. Nucleotide sequence analysis of a 2.3 kb fragment, derived from a 7 kb genomic clone, revealed an open reading frame encoding a protein of 487 amino acids (MW 53.8 kDa). The identities of the predicted amino acid sequence with its homologues from other species were between 24 and 47%. Functional domains previously defined for the SRP54-type proteins were present in the entamoebal sequence, such as the amino-terminal GTP binding domain (G domain) and the carboxy-terminal methionine rich domain (M domain). SRP54 mRNA contains an extra G residue at the 5' end, suggesting that capping of poly-A(+) transcripts is present in E. histolytica. Evolutionary analysis of the SRP54 based on phylogenetic inference placed the E. histolytica sequence as an early divergence of the eukaryotic tree. Although the function of the entamoebal homologue remains to be elucidated, the identification of the SRP54 gene constitutes the first evidence for SRP related proteins in protozoans.

Amino Acid Sequence↗

PubMed1994

The evolution of parasite manipulation of host behaviour: a theoretical analysis.

Parasite-induced modifications of host behaviour are known from a wide range of host-parasite associations. In many cases, these behavioural changes are thought to be adaptive and benefit the parasite by increasing its probability of successful transmission. However, in many cases, energy spent on host manipulation will not be available for other functions, such as growth. These trade-offs suggest that in the absence of other constraints, natural selection will optimize, and not maximize, the influence of parasites on host behaviour. This argument is developed and expanded into theoretical considerations of the evolution of host behaviour manipulation by parasites. Among populations of the same parasite species or among closely-related species, the optimal investment into manipulation, or optimal manipulative effort (ME*), of individual parasites is predicted to increase as (1) typical infrapopulation size decreases, (2) prevalence increases, (3) the longevity of the infected host, or of the parasite in its host, decreases, (4) passive transmission rates decrease, and (5) parasite fecundity decreases. This evolutionary analysis indicates that ecological and life history variables may have played an important role in the evolution of manipulation of host behaviour by parasites.

Adaptation, Physiological↗