SEARCH · PubMed Health

Results for “evolutionary analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources

PubMed1996

Evolution of chlorophyll and bacteriochlorophyll: the problem of invariant sites in sequence analysis.

Competing hypotheses seek to explain the evolution of oxygenic and anoxygenic processes of photosynthesis. Since chlorophyll is less reduced and precedes bacteriochlorophyll on the modern biosynthetic pathway, it has been proposed that chlorophyll preceded bacteriochlorophyll in its evolution. However, recent analyses of nucleotide sequences that encode chlorophyll and bacteriochlorophyll biosynthetic enzymes appear to provide support for an alternative hypothesis. This is that the evolution of bacteriochlorophyll occurred earlier than the evolution of chlorophyll. Here we demonstrate that the presence of invariant sites in sequence datasets leads to inconsistency in tree building (including maximum-likelihood methods). Homologous sequences with different biological functions often share invariant sites at the same nucleotide positions. However, different constraints can also result in additional invariant sites unique to the genes, which have specific and different biological functions. Consequently, the distribution of these sites can be uneven between the different types of homologous genes. The presence of invariant sites, shared by related biosynthetic genes as well as those unique to only some of these genes, has misled the recent evolutionary analysis of oxygenic and anoxygenic photosynthetic pigments. We evaluate an alternative scheme for the evolution of chlorophyll and bacteriochlorophyll.

Bacteriochlorophylls↗

PubMed2002

Evolution of behavior and neural control of the fast-start escape response.

The fast-start startle behavior is the primary mechanism of rapid escape in fishes and is a model system for examining neural circuit design and musculoskeletal function. To develop a dataset for evolutionary analysis of the startle response, the kinematics and muscle activity patterns of the fast-start were analyzed for four fish species at key branches in the phylogeny of vertebrates. Three of these species (Polypterus palmas, Lepisosteus osseus, and Amia calva) represent the base of the actinopterygian radiation. A fourth species (Oncorhynchus mykiss) provided data for a species in the central region of the teleost phylogeny. Using these data, we explored the evolution of this behavior within the phylogeny of vertebrates. To test the hypothesis that startle features are evolutionarily conservative, the variability of motor patterns and kinematics in fast-starts was described. Results show that the evolution of the startle behavior in fishes, and more broadly among vertebrates, is not conservative. The fast-start has undergone substantial change in suites of kinematics and electromyogram features, including the presence of either a one- or a two-stage kinematic response and change in the extent of bilateral muscle activity. Comparative methods were used to test the evolutionary hypothesis that changes in motor control are correlated with key differences in the kinematics and behavior of the fast-start. Significant evolutionary correlations were found between several motor pattern and behavioral characters. These results suggest that the startle neural circuit itself is not conservative. By tracing the evolution of motor pattern and kinematics on a phylogeny, it is shown that major changes in the neural circuit of the startle behavior occur at several levels in the phylogeny of vertebrates.

Animals↗

PubMed1999

Host-specific modulation of the selective constraints driving human immunodeficiency virus type 1 env gene evolution.

To address the evolution of human immunodeficiency virus type 1 (HIV-1) within a single host, we analyzed the HIV-1 C2-V5 env regions of both cell-free genomic-RNA- and proviral-DNA-derived clones. Sequential samples were collected over a period of 3 years from six untreated subjects (three typical progressors [TPs] and three slow progressors [SPs], all with a comparable length of infection except one. The evolutionary analysis of the C2-V5 env sequences performed on 506 molecular clones (253 RNA- and 253 DNA-derived sequences) highlighted a series of differences between TPs and SPs. In particular, (i) clonal sequences from SPs (DNA and RNA) showed lower nucleotide similarity than those from TPs (P = 0. 0001), (ii) DNA clones from SPs showed higher intra- and intersample nucleotide divergence than those from TPs (P < 0.05), (iii) higher host-selective pressure was generally detectable in SPs (DNA and RNA sequences), and (iv) the increase in the genetic distance of DNA and RNA sequences over time was paralleled by an increase in both synonymous (Ks) and nonsynonymous (Ka) substitutions in TPs but only in nonsynonymous substitutions in SPs. Several individual peculiarities of the HIV-1 evolutionary dynamics emerged when the V3, V4, and V5 env regions of both TPs and SPs were evaluated separately. These peculiarities, probably reflecting host-specific features of selective constraints and their continuous modulation, are documented by the dynamics of Ka/Ks ratios of hypervariable env domains.

Base Sequence↗

PubMed1993

[Molecular genotypes of hepatitis C virus and their divergence times].

We collected the nucleotide sequences of hepatitis C virus (HCV) from the international DNA data base DDBJ/EMBL/GenBank to carry out molecular evolutionary analysis of HCVs. Using these sequences, we constructed the phylogenetic trees for the 5' non-coding, Core, Env., E2/NS1, NS3, NS4 and NS5 regions of HCV. The number of nucleotide substitutions per site at all positions between all pairs of HCVs, for each region, were estimated by the 6-parameter method. Using these numbers, we constructed phylogenetic trees for each region of HCV by the neighbor-joining method. In these trees for the coding regions (Core, Env, E2/NS1, NS3, NS4 and NS5 regions), HCVs can be classified into two major and four minor genotypes, but into three major and six minor genotypes on the tree of the NS5 region. It appears that HCVs exist as at least two or three major and six minor types. The evolutionary rates of HCV was estimated to be about 10(-3) per site per year close to that of human immunodeficiency virus. The new genotypes of HCV may be therefore isolated elsewhere in the near future. Then, applying the distance between H77 and H90 strains to the phylogenetic trees, we estimated the divergence times of HCVs. The major genotypes diverged about 300-400 years ago from the ancestor virus and after then, each minor genotypes diversed about 200 years ago from their major genotypes. These data suggested that HCVs spread out all over the world during these hundred years.

Base Sequence↗

PubMed2000

Human mutations in glucose 6-phosphate dehydrogenase reflect evolutionary history.

Glucose 6-phosphate dehydrogenase (G6PD) is a cytosolic enzyme encoded by a housekeeping X-linked gene whose main function is to produce NADPH, a key electron donor in the defense against oxidizing agents and in reductive biosynthetic reactions. Inherited G6PD deficiency is associated with either episodic hemolytic anemia (triggered by fava beans or other agents) or life-long hemolytic anemia. We show here that an evolutionary analysis is a key to understanding the biology of a housekeeping gene. From the alignment of the amino acid (aa) sequence of 52 glucose 6-phosphate dehydrogenase (G6PD) species from 42 different organisms, we found a striking correlation between the aa replacements that cause G6PD deficiency in humans and the sequence conservation of G6PD: two-thirds of such replacements are in highly and moderately conserved (50-99%) aa; relatively few are in fully conserved aa (where they might be lethal) or in poorly conserved aa, where presumably they simply would not cause G6PD deficiency. This is consistent with the notion that all human mutants have residual enzyme activity and that null mutations are lethal at some stage of development. Comparing the distribution of mutations in a human housekeeping gene with evolutionary conservation is a useful tool for pinpointing amino acid residues important for the stability or the function of the corresponding protein. In view of the current explosive increase in full genome sequencing projects, this tool will become rapidly available for numerous other genes.

Amino Acid Sequence↗

PubMed1999

Evolution of ruminant Sarcocystis (Sporozoa) parasites based on small subunit rDNA sequences.

We present an evolutionary analysis of 13 species of Sarcocystis, including 4 newly sequenced species with ruminants as their intermediate host, based on complete small subunit rDNA sequences. Those species with ruminants as their intermediate host form a well-supported clade, and there are at least two major clades within this group, one containing those species forming microcysts and with dogs as their definitive host and the other containing those species forming macrocysts and with cats as their definitive host. Those species with nonruminants as their intermediate host form the paraphyletic sister group to these clades. Most of the species have considerable genotypic differences (differing in more than 100 nucleotide positions), except for S. buffalonis and S. hirsuta. There is a large suite of genotypic differences indicating that those species infecting ruminant and nonruminant hosts have had very different evolutionary histories, and similarly for the felid- and canid-infecting species. Furthermore, the rDNA sequences that represent the different structural regions of the rRNA molecule have very different genotypic behavior within Sarcocystis. The evolution of these regions should be functionally constrained, and their differences can be explained in terms of the importance of the nucleotide sequences to their functions.

Animals↗

PubMed2002

Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups.

The evolution of the human mitochondrial genome is characterized by the emergence of ethnically distinct lineages or haplogroups. Nine European, seven Asian (including Native American), and three African mitochondrial DNA (mtDNA) haplogroups have been identified previously on the basis of the presence or absence of a relatively small number of restriction-enzyme recognition sites or on the basis of nucleotide sequences of the D-loop region. We have used reduced-median-network approaches to analyze 560 complete European, Asian, and African mtDNA coding-region sequences from unrelated individuals to develop a more complete understanding of sequence diversity both within and between haplogroups. A total of 497 haplogroup-associated polymorphisms were identified, 323 (65%) of which were associated with one haplogroup and 174 (35%) of which were associated with two or more haplogroups. Approximately one-half of these polymorphisms are reported for the first time here. Our results confirm and substantially extend the phylogenetic relationships among mitochondrial genomes described elsewhere from the major human ethnic groups. Another important result is that there were numerous instances both of parallel mutations at the same site and of reversion (i.e., homoplasy). It is likely that homoplasy in the coding region will confound evolutionary analysis of small sequence sets. By a linkage-disequilibrium approach, additional evidence for the absence of human mtDNA recombination is presented here.

Africa↗

PubMed1994

Novel features of metazoan mtDNA revealed from sequence analysis of three mitochondrial DNA segments of the land snail Albinaria turrita (Gastropoda: Clausiliidae).

The mitochondrial DNA (mtDNA) size of the terrestrial gastropod Albinaria turrita was determined by restriction enzyme mapping and found to be approximately 14.5 kb. Its partial gene content and organization were examined by sequencing three cloned segments representing about one-fourth of the mtDNA molecule. Complete sequences of cytochrome c oxidase subunit II (COII), and ATPase subunit 8 (ATPase8), as well as partial sequences of cytochrome c oxidase subunit I (COI), NADH dehydrogenase subunit 6 (ND6), and the large ribosomal RNA (lrRNA) genes were determined. Nine putative tRNA genes were also identified by their ability to conform to typical mitochondrial tRNA secondary structures. An 82-nt sequence resembles a noncoding region of the bivalve Mytilus edulis, even though it might contain a tenth tRNA gene with an unusual 5-nt overlap with another tRNA gene. The genetic code of Albinaria turrita appears to be the same as that of Drosophila and Mytilus edulis. The structures of COI and COII are conservative, but those of ATPase8 and ND6 are diversified. The sequenced portion of the lrRNA gene (1,079 nt) is characterized by conspicuous deletions in the 5' and 3' ends; this gene represents the smallest coelomate lrRNA gene so far known. Sequence comparisons of the identified genes indicate that there is greater difference between Albinaria and Mytilus than between Albinaria and Drosophila. An evolutionary analysis, based on COII sequences, suggests a possible nonmonophyletic origin of molluskan mtDNA. This is supported also by the absence of the ATPase8 gene in the mtDNA of Mytilus and nematodes, while this gene is present in the mtDNA of Albinaria and Cepaea nemoralis and in all other known coelomate metazoan mtDNAs.

Amino Acid Sequence↗

PubMed1999

Cell-specific expression of genes of the lipid transfer protein family from Arabidopsis thaliana.

We have characterized three cDNAs from a gene family encoding lipid transfer proteins, LTP, from Arabidopsis thaliana (Wassilewskija). In addition to the already characterized Ltp1, our analysis includes Ltp2 and Ltp3, two sequences previously known as expressed sequence tags (EST) only. The deduced amino acid sequences of the three cDNAs share 56 to 57% identity and show unique tissue- and cell-specific expression. Genes Ltp1 and LTp2 are located within approximately 1.4 kb of each other in tandem orientation. RNA hydridizations showed that all three LTP are expressed in flowering meristems, flowers and developing seeds. Ltp1 is expressed in leaves in addition. Ltp3, though not Ltp2, is also expressed in a short segment of the stem close to the flowering meristem. In contrast to the epidermis-specific Ltp1, both Ltp2 and Ltp3 are not restricted to the epidermis, but are also expressed in sub-epidermal layers of the organs in which they are found. In the upper stem segment, Ltp3 is predominantly cortical. It appears that the expression of these three cDNAs is sufficient to account for the formation of LTP in all meristematic and expanding cells of the aboveground plant. Evolutionary analysis allows the conclusion that each Ltp belongs to a different sub-family of genes. Additionally, parsimony analysis provides evidence that several copies of Ltp genes already existed in ancestors of the Brassicaceae family.

Amino Acid Sequence↗

PubMed2003

A cattle-human comparative map built with cattle BAC-ends and human genome sequence.

As a step toward the goal of adding the cattle genome to those available for multispecies comparative genome analysis, 40,224 cattle BAC clones were end-sequenced, yielding 60,547 sequences (BAC end sequences, BESs) after trimming with an average read length of 515 bp. Cattle BACs were anchored to the human and mouse genome sequences by BLASTN search, revealing 29.4% and 10.1% significant hits (E < e-5), respectively. More than 60% of all cattle BES hits in both the human and mouse genomes are located within known genes. In order to confirm in silico predictions of orthologyand their relative position on cattle chromosomes, 84 cattle BESs with similarity to sequences on HSA11 were mapped using a cattle-hamster radiation hybrid (RH) panel. Resulting RH maps of BTA15 and BTA29 cover approximately 85% of HSA11 sequence, revealing a complex patchwork shuffling of segments not explained by a simple translocation followed by internal rearrangements. Overlay of the mouse conserved syntenies onto HSA11 revealed that segmental boundaries appear to be conserved in all three species. The BAC clone-based comparative map provides a foundation for the evolutionary analysis of mammalian karyotypes and for sequencing of the cattle genome.

Animals↗

PubMed1999

The evolutionary ecology of dominance-recessivity.

An "adaptive dynamics" modelling approach to the evolution of dominance-recessivity is presented. In this approach, fitness derives from an explicit ecological scenario, and both evolutionary attractivity and invasibility of resident populations are examined. The ecology consists of a within-individual part representing a locus with regulated activity and a between-individual part that is a two-patch soft selection model. Evolutionary freedom is allowed at a single locus. The evolutionary analysis considers directed random walks on trait space, generated by repeated invasions of mutants. The phenotype of an individual is determined by allelic parameters. Mutations can have two effects: they either affect the affinity of the promoter sequence for transcription factors, or they affect the gene product. The dominance interaction between alleles derives from their promoter affinities. Additive genetics is evolutionarily unstable when selection and evolution maintain two alleles in the population. In such a situation, dominance interactions can become stationary and close to additive genetics or they continue to evolve at a very slow pace towards dominance-recessivity. The probability that a specific dominance interaction will evolve depends on the relative mutation rate of promoter compared to gene product and the distribution of mutational effect sizes. Either allele in the dimorphism can become dominant, and dominance-recessivity is always most likely to evolve. Evolution then approaches a population state where every phenotype has maximum viability in one of the two patches. When the within-individual part is replaced by a housekeeping locus that codes for a metabolic enzyme, evolution favours a population of two alleles under the same conditions as for a regulated locus. In the case of a housekeeping gene, however, the evolutionary dynamical system approaches a population state where the heterozygote and only one homozygote phenotype are equivalent to the optimum phenotypes in the two patches.

Alleles↗

PubMed2000

Distribution of choline acetyltransferase immunoreactivity in the brain of an elasmobranch, the lesser spotted dogfish (Scyliorhinus canicula).

Although the distribution of cholinergic cells is remarkably similar across the vertebrate species, no data are available on more primitive species, such as cartilaginous fishes. To extend the evolutionary analysis of the cholinergic systems, we studied the distribution of cholinergic neurons in the brain and rostral spinal cord of Scyliorhinus canicula by immunocytochemistry using an antibody against the enzyme choline acetyltransferase (ChAT). Western blot analysis of brain extracts of dogfish, sturgeon, trout, and rat showed that this antibody recognized similar bands in the four species. Putative cholinergic neurons were observed in most brain regions, including the telencephalon, diencephalon, cerebellum, and brainstem. In the retrobulbar region and superficial dorsal pallium of the telencephalon, numerous small pallial cells were ChAT-like immunoreactive. In addition, tufted cells of the olfactory bulb and some cells in the lateral pallium showed faint immunoreactivity. In the preoptic-hypothalamic region, ChAT-immunoreactive (ChAT-ir) cells were found in the preoptic nucleus, the vascular organ of the terminal lamina, and a small population in the caudal tuber. In the epithalamus, the pineal photoreceptors were intensely positive. Many cells of the habenula were faintly ChAT-ir, but the neuropil of the interpeduncular nucleus showed intense ChAT immunoreactivity. In the pretectal region, ChAT-ir cells were observed only in the superficial pretectal nucleus. In the brainstem, the somatomotor and branchiomotor nuclei, the octavolateral efferent nucleus, and a cell group just rostral to the Edinger-Westphal (EW) nucleus contained ChAT-ir neurons. In addition, the trigeminal mesencephalic nucleus, the nucleus G of the isthmus, some locus coeruleus cells, and some cell populations of the vestibular nuclei and of the electroreceptive nucleus of the octavolateral region exhibited ChAT immunoreactivity. In the reticular areas of the brainstem, the nucleus of the medial longitudinal fascicle, many reticular neurons of the rhombencephalon, and cells of the nucleus of the lateral funiculus were immunoreactive to this antibody. In the cerebellum, Golgi cells of the granule cell layer and some cells of the cerebellar nucleus were also ChAT-ir. In the rostral spinal cord, ChAT immunoreactivity was observed in cells of the motor column, the dorsal horn, the marginal nucleus (a putative stretch-receptor organ), and in interstitial cells of the ventral funiculus. These results demonstrate for the first time that cholinergic neurons are distributed widely in the central nervous system of elasmobranchs and that their cholinergic systems have evolved several characteristics that are unique to this group.

Acetylcholine↗

PubMed1998

Plant homeobox genes: many functions stem from a common motif.

Homeodomain-containing transcription factors play a variety of important roles in plant, animal, and fungal development. Mutational and evolutionary analysis is beginning to pinpoint specific roles of homeobox genes in plant meristem function. Even though many different plant homeobox genes encode very similar homeodomain sequences, overexpression studies suggest the existence of several levels of regulation that may specify the functions of the different proteins. Recent analysis of the maize Knotted1 gene and its orthologue in barley demonstrates some of these regulatory processes.

Amino Acid Sequence↗

PubMed2000

TT virus infection in patients with chronic liver disease of unknown etiology.

The role of a novel virus, designated as TT virus (TTV), as a cause of chronic liver disease has not been well defined. We investigated the prevalence of TTV among 69 patients with chronic liver disease of unknown etiology and 50 volunteer blood donors with normal transaminase levels. TTV DNA was amplified by polymerase chain reaction (PCR) by using two different sets of primers: one based on the sequence of the original N22 clone within the open reading frame 1 (set A) and the other derived from the untranslated region (set B). The prevalence of TTV detected by PCR primers set A only, set B only, and in total (by either set A or B) was 11 (31%), 31 (86%), and 31 (86%) of 36 patients with chronic hepatitis; 2 (40%), 4 (80%), and 4 (80%) of 5 with cirrhosis; 11 (39%), 17 (61%), and 22 (79%) of 28 with hepatocellular carcinoma; and 9 (18%), 39 (78%), and 40 (80%) of 50 volunteer blood donors, respectively. Of the interpretable 25 PCR products amplified with primers set A, 9 were classified as genotype 1a, 10 as genotype 1b, 4 as genotype 2, 1 as genotype 3, and 1 as genotype 4. Molecular evolutionary analysis did not suggest any particular strains of TTV that might be associated with chronic liver disease. The nucleotide sequences of the untranslated region on which PCR primers set B were designed were highly conserved, and the interpretable 22 PCR products amplified with primers set B were not clearly divisible into distinct genotypes. Our findings provided no evidence that TTV is a causative agent of chronic liver disease.

Chronic Disease↗

PubMed1994

Evolution of cytochrome oxidase, an enzyme older than atmospheric oxygen.

Cytochrome oxidase is a key enzyme in aerobic metabolism. All the recorded eubacterial (domain Bacteria) and archaebacterial (Archaea) sequences of subunits 1 and 2 of this protein complex have been used for a comprehensive evolutionary analysis. The phylogenetic trees reveal several processes of gene duplication. Some of these are ancient, having occurred in the common ancestor of Bacteria and Archaea, whereas others have occurred in specific lines of Bacteria. We show that eubacterial quinol oxidase was derived from cytochrome c oxidase in Gram-positive bacteria and that archaebacterial quinol oxidase has an independent origin. A considerable amount of evidence suggests that Proteobacteria (Purple bacteria) acquired quinol oxidase through a lateral gene transfer from Gram-positive bacteria. The prevalent hypothesis that aerobic metabolism arose several times in evolution after oxygenic photosynthesis, is not sustained by two aspects of the molecular data. First, cytochrome oxidase was present in the common ancestor of Archaea and Bacteria whereas oxygenic photosynthesis appeared in Bacteria. Second, an extant cytochrome oxidase in nitrogen-fixing bacteria shows that aerobic metabolism is possible in an environment with a very low level of oxygen, such as the root nodules of leguminous plants. Therefore, we propose that aerobic metabolism in organisms with cytochrome oxidase has a monophyletic and ancient origin, prior to the appearance of eubacterial oxygenic photosynthetic organisms.

Aerobiosis↗

PubMed2003

Hepatitis C virus molecular epidemiology in Uzbekistan.

The aim of this study was to identify hepatitis C virus (HCV) genotypes and to estimate their prevalence in various risk groups and the regional distribution in Uzbekistan. Preliminary serological screening of 1,269 subjects revealed 6.5% anti-HCV-positive in a general population, 27.1% in patient groups, and 51.7% among intravenous drug users. HCV genotypes of 104 anti-HCV-positive subjects were determined using a PCR-genotyping system in core region, and the results were supported by nucleotide sequencing of the NS5B region. Genotype 1b identified in total 64.2%, was the most prevalent. The genotype 3a identified in 25.0% was the second one distributed. HCV genotypes 2a, 1a, 2b, and 3b were identified in 3.8%, 2.9%, 2.9%, and 1.0% of cases, respectively. The intravenous drug users were distinguished from other groups by having the highest prevalence of genotype 3a, i.e., 50.0%, higher than the 33.3% for genotype 1b in this group. Geographically, genotype 1b was common; genotype 3a was also found frequently in all three regions. Uncommon HCV genotypes (1a, 2a, 2b, and 3b) were found in comparatively greater variability in the western region. Molecular evolutionary analysis based on the NS5B region did not reveal specific clustering or indigenous strains among Uzbekistan HCV isolates. In summary, two main mechanisms of HCV infection distribution were observed in Uzbekistan: HCV 1b genotype infection is widespread through blood products, and HCV 3a genotype infection is spreading through the growing number of intravenous drug users.

Adolescent↗

PubMed2025

Coronavirus Cryptic Landscape and Draft Genome of a Novel CoV Clade Related to MERS From Bats Circulating in Northeastern Brazil.

We identified seven distinct coronaviruses (CoVs) in bats from Brazil, classified into 229E-related (Alpha-CoV), Nobecovirus, Sarbecovirus, and Merbecovirus (Beta-CoV), including one closely related to MERS-like CoV with 82.8% genome coverage. To accomplish this, we screened 423 oral and rectal swabs from 16 different bat species using molecular assays, RNA sequencing, and evolutionary analysis. Notably, gaps in the spike-encoding gene led us to design new primers and perform Sanger sequencing, which revealed high similarities to MERS-related (MERSr) CoV strains found in humans and camels. Additionally, we identified key residues in the receptor-binding domain (RBD) of the spike protein, suggesting potential interactions with DPP4, the receptor for MERSr-CoV. Our analyses also revealed evidence of recombination involving our laboratory-produced sequences. These findings highlight the extensive genetic diversity of CoVs, the presence of novel viral lineages, and the occurrence of recombination events among bat CoVs circulating in Brazil, underscoring the critical role bats play as reservoirs for emerging viruses and emphasizing the necessity of ongoing surveillance to monitor the public health risks associated with CoV spillover events.

Chiroptera↗

PubMed2001

Identification of a nuclear variant of MGEA5, a cytoplasmic hyaluronidase and a beta-N-acetylglucosaminidase.

MGEA5 was originally identified to be a novel human hyaluronidase, which is immunogenic in meningioma patients. Recently an N-acetylglucosaminidase was reported with identical sequence. Here, we define the origin of a splice variant by determining the genomic organization of the mgea5 gene. We find the splice variant missing a putative acetyltransferase domain of MGEA5. As for evolutionary analysis, we show that the MGEA5 is highly conserved in higher eukaryotes. As for expression analysis, we find both mRNA variants ubiquitously expressed in various human tissues and throughout mouse development. We generated polyclonal antibodies against MGEA5s/5 and identified proteins of 75 and 130 kDa, indicating posttranslational modifications of the larger protein. Cell fractionation revealed the cytoplasmic/cytoskeletal localization of the 130-kDa protein and the nuclear localization of the 75-kDa protein. We propose a model in which MGEA5 functions both as a hyaluronidase and an N-acetylglucosaminidase.

Acetylglucosaminidase↗