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The remarkable evolutionary history of the human amylase genes.

Analysis of the structures of the human amylase genes has demonstrated that this multigene family contains at least five tandem gene copies, closely related in sequence but with distinct tissue specific expression. The structures of the genes demonstrate that the human salivary amylase gene was derived from a preexisting pancreatic amylase gene. Insertion of a retrovirus upstream of the amylase gene is responsible for the alteration in tissue specificity. A parotid specific enhancer has been identified within the retrovirus by expression studies in transgenic mice. The independent origin of salivary amylase in rodents and primates suggests that there has been strong evolutionary selection for amylase in saliva. The amylase genes demonstrate a novel mechanism for evolution of new patterns of tissue specific gene expression.

Amylases↗

Comparative analysis of regulatory transcription factors in Schizosaccharomyces pombe and budding yeasts.

Regulatory transcription factors (rTFs), which bind specific DNA sequences in the regulatory regions of genes and subsequently activate or repress transcription, play a central role in programming genomic expression. The number of rTFs in a species might therefore reflect its functional complexity. For simple organisms like yeast, a relatively small number of rTFs might be expected that is fairly constant between yeast species. We show that the budding yeast, Saccharomyces cerevisiae, contains 201 rTfs, which is one of the largest rTF numbers found in yeast species for which genome sequences are available. This is a much higher number than the 129 rTFs found in the fission yeast, Schizosaccharomyces pombe, which is currently the yeast with the lowest number of rTFs. Comparative analysis of several different budding yeast species shows that most of the 'extra' rTFs found in S. cerevisiae were probably acquired as a result of a whole genome duplication (WGD) event that occurred in an ancestor of a subset of budding yeast species. However, we also show that budding yeast species that have not been affected by the WGD contain a greater number of rTFs than S. pombe (mean = 145). Thus, two or more mechanisms have led to the 60% increase in rTFs in S. cerevisiae compared to S. pombe. This difference may correlate with a more extensive functional divergence in budding yeasts compared to fission yeasts. The relatively small number of rTFs in S. pombe make this organism an attractive model for global studies of mechanisms that programme gene expression.

Evolution, Molecular↗

Improving the speed of the genetic toggle switch without sacrificing its dynamic stability.

Determinants of the switching speed of the genetic toggle switch remain unknown. Analysis shows that the decay rate of proteins predominantly sets the speed limit, but its modification introduces a trade-off between increased speed and decreased bistability. Incorporating protein-modifying enzymes into the switch gives extra degrees of freedom to address this trade-off. The condition for bistability when such enzymes are incorporated is derived. Under this condition, speed increases with the maximal rate of gene expression.

Animals↗

Characterisation of an amphioxus Fringe gene and the evolution of the vertebrate segmentation clock.

In mouse and chick embryos, cyclic expression of lunatic fringe has an important role in the regulation of mesoderm segmentation. We have isolated a Fringe gene from the protochordate amphioxus. Amphioxus is the closest living relative of the vertebrates, and has mesoderm that is definitively segmented in a manner that is similar to, and probably homologous with, that of vertebrates. AmphiFringe is placed basal to vertebrate Fringe genes in molecular phylogenetic analyses, indicating that the duplications that formed radical-, manic- and lunatic fringe are specific to the vertebrate lineage. AmphiFringe expression was detected in the anterior neural plate of early neurulae, where it resolved into a series of segmental patches by the mid-neurulae stage. No AmphiFringe transcripts were detected in the mesoderm. Based on these observations, we propose a model depicting a successive recruitment of Fringe in the maintenance then regulation of segmentation during vertebrate evolution.

Amino Acid Sequence↗

Comprehensive identification and evolutionary analysis of the Wnt gene family in bivalves: Insights into the larval development of the noble scallop Chlamys nobilis.

The Wnt gene family regulates fundamental developmental processes in metazoans, but its evolutionary composition and developmental deployment in bivalves remain largely unresolved. Here, we performed a comparative genomic analysis of Wnt genes in 19 bivalve species and examined developmental expression profiles in the noble scallop Chlamys nobilis, with Crassostrea gigas and Chlamys farreri used for cross-species comparison. A total of 235 Wnt genes were identified and assigned to 12 subfamilies. No reliable Wnt3 ortholog was detected in any analyzed bivalve, supporting the view that Wnt3 loss occurred early during lophotrochozoan evolution rather than representing a lineage-specific absence. Most Wnt proteins retained the conserved WNT domain, indicating strong structural conservation, whereas lineage-specific copy-number variation and gene loss were observed among species. C. farreri and C. gigas each retained 12 Wnt genes and lacked Wnt3, whereas C. nobilis lacked Wnt3, Wnt7, and Wnt16. Developmental transcriptome analysis and RT-qPCR revealed clear stage-specific expression patterns. In C. gigas, Wnt2/10/A were highly expressed during earlydevelopment and peaked around the D-shaped larval stage, while Wnt8 and Wnt11 showed distinct stage-specific peaks. By contrast, Wnt1/5/6/9 were more active during later larval development or juvenile formation. These results provide a comparative framework for bivalve Wnt evolution and identify candidate Wnt genes potentially involved in larval development and aquaculture-relevant developmental transitions.

Animals↗

Nucleotide sequence, evolution, and expression of the fetal globin gene of the spider monkey Ateles geoffroyi.

The single gamma-globin gene of the New World spider monkey Ateles geoffroyi is similar to other primate genes of the beta-globin gene cluster ("beta-like" globin genes). The number of nonsynonymous nucleotide substitutions between the coding regions of Ateles and other primate gamma-globin genes suggests that the Platyrrhine and Catarrhine evolutionary lines diverged approximately equal to 40 million years ago, an estimate reasonably consistent with the fossil record. However, the number of synonymous coding region and noncoding base differences is much smaller than predicted by various molecular "clocks." This suggests that the rate of synonymous coding and noncoding base substitution has not been constant per absolute time in primate lineages. Expression of the cloned Ateles gamma-globin gene in cultured monkey cells showed that the sequence AAUAAA near the mRNA 3' terminus is not sufficient to define the site of transcript polyadenylylation.

Amino Acid Sequence↗

Evolution of myelin proteolipid proteins: gene duplication in teleosts and expression pattern divergence.

The coevolution of neurons and their supporting glia to the highly specialized axon-myelin unit included the recruitment of proteolipids as neuronal glycoproteins (DMbeta, DMgamma) or myelin proteins (DMalpha/PLP/DM20). Consistent with a genome duplication at the root of teleosts, we identified three proteolipid pairs in zebrafish, termed DMalpha1 and DMalpha2, DMbeta1 and DMbeta2, DMgamma1 and DMgamma2. The paralogous amino acid sequences diverged remarkably after gene duplication, indicating functional specialization. Each proteolipid has adopted a distinct spatio-temporal expression pattern in neural progenitors, neurons, and in glia. DMalpha2, the closest homolog to mammalian PLP/DM20, is coexpressed with P0 in oligodendrocytes and upregulated after optic nerve lesion. DMgamma2 is expressed in multipotential stem cells, and the other four proteolipids are confined to subsets of CNS neurons. Comparing protein sequences and gene structures from birds, teleosts, one urochordate species, and four invertebrates, we have reconstructed major steps in the evolution of proteolipids.

Amino Acid Sequence↗

Novel insights into lung transplant rejection by microarray analysis.

Gene expression microarrays can estimate the prevalence of mRNA for thousands of genes in a small sample of cells or tissue. Organ transplant researchers are increasingly using microarrays to identify specific patterns of gene expression that predict and characterize acute and chronic rejection, and to improve our understanding of the mechanisms underlying organ allograft dysfunction. We used microarrays to assess gene expression in bronchoalveolar lavage cell samples from lung transplant recipients with and without acute rejection on simultaneous lung biopsies. These studies showed increased expression during acute rejection of genes involved in inflammation, apoptosis, and T-cell activation and proliferation. We also studied gene expression during the evolution of airway obliteration in a murine heterotopic tracheal transplant model of chronic rejection. These studies demonstrated specific patterns of gene expression at defined time points after transplantation in allografts, whereas gene expression in isografts reverted back to that of native tracheas within 2 wk after transplantation. These studies demonstrate the potential power of microarrays to identify biomarkers of acute and chronic lung rejection. The application of new genetic, genomic, and proteomic technologies is in its infancy, and the microarray-based studies described here are clearly only the beginning of their application to lung transplantation. The massive amount of data generated per tissue or cell sample has spawned an outpouring of invention in the bioinformatics field, which is developing methodologies to turn data into meaningful and reproducible clinical and mechanistic inferences.

Animals↗

A test for adaptive change in DNA sequences controlling transcription.

Spatial and temporal differences in gene expression in early development result from the interaction of transcription factors with enhancer and silencer sequences in DNA. The evolution of the developmental process thus involves changes in the DNA sequences that bind transcription factors. Here we advocate a non-parametric statistical test-comparing levels of polymorphism and fixed substitutions between species -to look for evidence of adaptive evolution in sequences controlling gene expression. The test is illustrated by DNA sequence changes in the proximal part of the 'zebra' elements in the fushi terazu gene of the Drosophila melanogaster species group, which yield significant evidence for adaptive substitutions. (This is despite highly significant evidence that all parts of the sequence have been subject to strong selective constraint). The test can be applied generally to investigate adaptive evolution in the control of gene expression.

Animals↗

Strong evolutionary conservation of broadly expressed protein isoforms in the troponin I gene family and other vertebrate gene families.

It is well established that different protein classes undergo molecular evolution at different rates, presumably reflecting differing functional constraints. However, it is also the case that different isoforms of the "same" protein, encoded by a multigene family, may evolve at different rates. Here I report a relationship within gene families between isoform evolutionary rate and gene expression profile: Broadly expressed isoforms show stronger sequence conservation than do narrowly expressed isoforms. This observation emerged initially from cDNA cloning and sequencing studies, described here, of a vertebrate gene family encoding three differentially expressed isoforms of the muscle protein troponin I. However, the expression breadth/sequence conservation relationship applies to vertebrate gene families in general. In a broad and arbitrary survey sampling of sequence data on well-characterized vertebrate gene families, I found that in 14/15 families the most strongly conserved isoform was the most broadly expressed isoform, or one of several similarly broadly expressed isoforms. Broadly expressed isoforms are presumably subjected to greater negative selection pressure because they must function in a more diverse biochemical environment than do narrowly expressed isoforms. The expression breadth/evolutionary rate relationship has several interesting implications regarding the overall process of gene family evolution by duplication/divergence from ancestral genes.

Amino Acid Sequence↗

Differing expression patterns and evolution of the rat kininogen gene family.

The present investigation using molecular cloning and sequence analysis concerns the examination of the molecular basis for different expression patterns of two types of the rat kininogen genes. We show that the low molecular weight and high molecular weight forms of K kininogens are produced from a single gene through alternative usage of two 3'-coding regions, whereas only the low molecular weight forms of T kininogens are generated as a result of several mutational changes in the high molecular weight-specifying regions of both T-I and T-II kininogen genes. The mutational changes include a nucleotide substitution at the polyadenylation/processing signal site, nucleotide deletions resulting in the frame-shift mutation, and an insertion of the type 2 Alu-equivalent sequence. Because kininogens represent a multifunctional protein comprising the proteinase-inhibitory activity, the kinin moiety, and the clotting activity, these results present evidence indicating the molecular basis for the disappearance of a part of the gene functions. We also show that the K and T kininogen genes as well as the two T kininogen genes are extremely homologous, excluding and including the above mutational changes, respectively. These structural relationships allow us to envisage evolutionary processes for the generation of the rat kininogen gene family, particularly for the disappearance of a part of the gene functions.

Animals↗

The life-cycle of operons.

Operons are a major feature of all prokaryotic genomes, but how and why operon structures vary is not well understood. To elucidate the life-cycle of operons, we compared gene order between Escherichia coli K12 and its relatives and identified the recently formed and destroyed operons in E. coli. This allowed us to determine how operons form, how they become closely spaced, and how they die. Our findings suggest that operon evolution may be driven by selection on gene expression patterns. First, both operon creation and operon destruction lead to large changes in gene expression patterns. For example, the removal of lysA and ruvA from ancestral operons that contained essential genes allowed their expression to respond to lysine levels and DNA damage, respectively. Second, some operons have undergone accelerated evolution, with multiple new genes being added during a brief period. Third, although genes within operons are usually closely spaced because of a neutral bias toward deletion and because of selection against large overlaps, genes in highly expressed operons tend to be widely spaced because of regulatory fine-tuning by intervening sequences. Although operon evolution may be adaptive, it need not be optimal: new operons often comprise functionally unrelated genes that were already in proximity before the operon formed.

Bacillus subtilis↗

Evolutionary genetics. The silence of the genes.

A low mutation rate is required for the evolution of large genomes. But is the repression of inadvertent gene expression also important, and is the evolution of complexity limited by the efficiency of noise reduction?

Animals↗

Molecular Evolution and Expression Analysis of the ADH Gene Family in Apple Bud Mutants.

Alcohol dehydrogenase (ADH) catalyzes the reduction of aldehydes to alcohols, key precursor substrates for volatile ester biosynthesis, which determines the characteristic aroma of apple fruit. However, a comprehensive genome-wide investigation of the ADH gene family in apple has been lacking. In this study, we systematically identified ADH genes in the apple genome using integrated bioinformatics approaches, including phylogenetic analysis, synteny evaluation, promoter cis-element prediction, codon usage bias assessment, and protein interaction network modeling. Expression patterns were examined through transcriptomic data and validated by RT-qPCR analysis across different organs and among 'Red Delicious' and its four bud mutant lines. We identified 44 ADH genes, with 12 forming a prominent cluster on chromosome 1. RT-qPCR analysis revealed that MdADH20 was dramatically upregulated in the 'Red Chief' mutant (relative expression of 59.38), suggesting its pivotal role. Phylogenetic analysis revealed a close evolutionary relationship with wild strawberry. The encoded proteins were generally stable and predominantly localized to the cytoplasm. Promoter analysis showed enrichment of growth/development-related and ARE elements, while codon usage analysis identified AGA, GCU, GUU, and CUU as preferred codons. Protein interaction prediction suggested MdADH19 and MdADH20 as hub proteins. Expression profiling and RT-qPCR further identified MdADH20 as a core candidate gene, characterized by its stable and high expression, particularly in the 'Red Delicious' mutant. Its central position in the predicted protein-protein interaction network suggests a potential regulatory role in the aroma biosynthesis pathway of apple fruit. This study provides the first systematic genome-wide characterization of the apple ADH gene family, establishing a theoretical groundwork for deciphering aroma biosynthesis mechanisms and offering potential target genes for flavor improvement through bud mutation breeding strategies.

ADH gene family↗

An embryonic pattern of expression of a human fetal globin gene in transgenic mice.

During the evolution of the beta-globin family gene in vertebrates, different globin genes acquired different developmental patterns of expression. In mammals, specific 'embryonic' beta-like globins are synthesized in the earliest erythroid cells, which differentiate in the yolk sac of the embryo. In most mammals the embryonic globin chains are replaced by 'adult' beta-globins in fetal and adult erythrocytes, which arise in the liver and bone marrow, respectively. However, in simian primates (including humans), a distinct 'fetal' type of beta-like globin chain predominates in fetal erythroid cells. Based on the pattern of DNA sequence homologies between different mammalian species, these fetal globin genes, G gamma and A gamma, are thought to have descended from an ancestral gene, 'proto-gamma', which was embryonic in its pattern of expression. In the mouse, as well as in most other mammalian species, the descendants of the proto-gamma gene continue to function as embryonic genes. To investigate the evolutionary changes that led to the 'fetal recruitment' of the gamma-globin genes in primates, we have introduced the cloned human G gamma-globin gene into the mouse germ line. We report here that the human G gamma gene reverts to an embryonic pattern of expression in the developing mouse. This observation suggests that during evolution a shift occurred in the timing of expression of a trans-acting signal controlling the proto-gamma gene.

Animals↗

Conservation and evolution of gene coexpression networks in human and chimpanzee brains.

Comparisons of gene expression between human and non-human primate brains have identified hundreds of differentially expressed genes, yet translating these lists into key functional distinctions between species has proved difficult. Here we provide a more integrated view of human brain evolution by examining the large-scale organization of gene coexpression networks in human and chimpanzee brains. We identify modules of coexpressed genes that correspond to discrete brain regions and quantify their conservation between the species. Module conservation in cerebral cortex is significantly weaker than module conservation in subcortical brain regions, revealing a striking gradient that parallels known evolutionary hierarchies. We introduce a method for identifying species-specific network connections and demonstrate how differential network connectivity can be used to identify key drivers of evolutionary change. By integrating our results with comparative genomic sequence data and estimates of protein sequence divergence rates, we confirm a number of network predictions and validate these findings. Our results provide insights into the molecular bases of primate brain organization and demonstrate the general utility of weighted gene coexpression network analysis.

Animals↗

Localization of the alpha 7 integrin gene (ITGA7) on human chromosome 12q13: clustering of integrin and Hox genes implies parallel evolution of these gene families.

Expression of the alpha 7 integrin gene (ITGA7) is developmentally regulated during the formation of skeletal muscle. Increased levels of expression and production of isoforms containing different cytoplasmic and extracellular domains accompany myogenesis. To determine whether a single or multiple alpha 7 genes underlie the structural diversity in this alpha chain that accompanies development, we have examined the rat and human genomes by Southern blotting and in situ hybridization. Our results demonstrate that there is only one alpha 7 gene in both the rat and the human genomes. In the human, ITGA7 is present on chromosome 12q13. Phylogenetic analysis of the integrin alpha chain sequences suggests that the early integrin genes evolved in two pathways to form the I-integrins and the non-I-integrins. The I-integrin alpha chains contain an additional sequence of approximately 180 amino acids and arose as a result of an early insertion into the non-I-gene. The I-chain subfamily further evolved by duplications within the same chromosome. The non-I-integrin alpha chain genes are localized in clusters on chromosomes 2, 12, and 17, and this closely coincides with the localization of the human homeobox gene clusters. Non-I-integrin alpha chain genes appear to have evolved in parallel and in proximity to the Hox clusters. Thus, the Hox genes that underlie the design of body structure and the Integrin genes that underlie informed cell-cell and cell-matrix interactions appear to have evolved in parallel and coordinate fashions.

Amino Acid Sequence↗

High-resolution FISH mapping of the rat alpha2u-globulin multigene family.

The rat alpha2u-globulins are a group of similar proteins that are encoded by a family of approximately 20 genes located a single locus of < or =880 kbp on Chromosome (Chr) 5q. Individual members of this gene family demonstrate complex tissue, hormonal, and developmental expression patterns despite a high degree of sequence similarity among the members and consequently provide an interesting system for studying the evolution of differential gene expression. Hybridization analysis indicated that gene classes, similar to those identified at the homologous MUP locus in the mouse, do not exist within the rat alpha2u-globulin locus. Furthermore, cross-hybridization analysis revealed the presence of conserved sequences in the 5' and 3' regions flanking the alpha2u-globulin genes, some of which were present in an inverted orientation. We have used high-resolution fiber FISH to examine the structural organization of the alpha2u-globulin locus, and found the genes to be arranged as an array of both direct and inverted repeats. The organization of the rat alpha2u-globulin genes differs from the MUP genes and suggests different evolutionary events have reorganized these homologous sets of genes.

Alpha-Globulins↗