Streptococcus mutans is the leading cause of dental caries (tooth decay) worldwide and is considered to be the most cariogenic of all of the oral streptococci. The genome of S. mutans UA159, a serotype c strain, has been completely sequenced and is composed of 2,030,936 base pairs. It contains 1,963 ORFs, 63% of which have been assigned putative functions. The genome analysis provides further insight into how S. mutans has adapted to surviving the oral environment through resource acquisition, defense against host factors, and use of gene products that maintain its niche against microbial competitors. S. mutans metabolizes a wide variety of carbohydrates via nonoxidative pathways, and all of these pathways have been identified, along with the associated transport systems whose genes account for almost 15% of the genome. Virulence genes associated with extracellular adherent glucan production, adhesins, acid tolerance, proteases, and putative hemolysins have been identified. Strain UA159 is naturally competent and contains all of the genes essential for competence and quorum sensing. Mobile genetic elements in the form of IS elements and transposons are prominent in the genome and include a previously uncharacterized conjugative transposon and a composite transposon containing genes for the synthesis of antibiotics of the gramicidin͞bacitracin family; however, no bacteriophage genomes are present.

The 1,815,783-bp genome of a serotype M49 strain of Streptococcus pyogenes (group A streptococcus [GAS]), strain NZ131, has been determined. This GAS strain (FCT type 3; emm pattern E), originally isolated from a case of acute post-streptococcal glomerulonephritis, is unusually competent for electrotransformation and has been used extensively as a model organism for both basic genetic and pathogenesis investigations. As with the previously sequenced S. pyogenes genomes, three unique prophages are a major source of genetic diversity. Two clustered regularly interspaced short palindromic repeat (CRISPR) regions were present in the genome, providing genetic information on previous prophage encounters. A unique cluster of genes was found in the pathogenicity island-like emm region that included a novel Nudix hydrolase, and, further, this cluster appears to be specific for serotype M49 and M82 strains. Nudix hydrolases eliminate potentially hazardous materials or prevent the unbalanced accumulation of normal metabolites; in bacteria, these enzymes may play a role in host cell invasion. Since M49 S. pyogenes strains have been known to be associated with skin infections, the Nudix hydrolase and its associated genes may have a role in facilitating survival in an environment that is more variable and unpredictable than the uniform warmth and moisture of the throat. The genome of NZ131 continues to shed light upon the evolutionary history of this human pathogen. Apparent horizontal transfer of genetic material has led to the existence of highly variable virulence-associated regions that are marked by multiple rearrangements and genetic diversification while other regions, even those associated with virulence, vary little between genomes. The genome regions that encode surface gene products that will interact with host targets or aid in immune avoidance are the ones that display the most sequence diversity. Thus, while natural selection favors stability in much of the genome, it favors diversity in these regions. Group A streptococcus ([GAS] Streptococcus pyogenes)causes a wide range of human diseases ranging from uncomplicated pharyngitis to life-threatening invasive disease. Acute post-streptococcal glomerulonephritis (APSGN) is one of the nonsuppurative sequelae that can occur following a GAS infection; the other common postinfection sequelae are rheumatic heart disease. Worldwide, it is estimated that approximately 470,000 cases of APSGN occur annually (23). Children and young adults are affected most commonly, with males having twice the incidence as females (74). By the 1940s, evidence was found that streptococcal skin infections were associated with APSGN, and these infections usually did not cause rheumatic fever, leading to the hypothesis that certain GAS strains were "rheumatogenic" while others were "nephritogenic" (41, 72). Further, divergent seasonal patterns of peak incidence exist separating nephritogenic and rheumatogenic GAS, with APSGN cases peaking in the late summer simultaneously with skin infections w...

Mammalian alcohol dehydrogenases (ADH) 3 form a complex enzyme system based on amino-acid sequence, functional properties, and gene expression pattern. At least four mouse Adh genes are known to encode dierent enzyme classes that share less than 60% amino-acid sequence identity. Two ADH-containing and overlapping C57BL/6 bacterial arti®cial chromosome clones, RP23-393J8 and -463H24, were identi®ed in a library screen, physically mapped, and sequenced. The gene order in the complex and two new mouse genes, Adh5a and Adh5b, and a pseudogene, Adh5ps, were obtained from the physical map and sequence.The mouse genes are all in the same transcriptional orientation in the order Adh4-Adh1-Adh5a-Adh5b-Adh5ps-Adh2-Adh3. A phylogenetic tree analysis shows that adjacent genes are most closely related suggesting a series of duplication events resulted in the gene complex. Although mouse and human ADH gene clusters contain at least one gene for ADH classes I±V, the human cluster contains 3 class I genes while the mouse cluster has two class V genes plus a class V pseudogene.Keywords: alcohol dehydrogenase; mouse; gene complex.The alcohol dehydrogenases (ADHs; EC 1.1.1.1) are zinccontaining, dimeric enzymes found in the cytosolic fraction of the cell that are capable of reversible oxidation of a spectrum of primary and secondary alcohols to the corresponding aldehydes and ketones. Mammalian ADHs currently known are grouped into six distinct classes [1±3] with members of different classes sharing less than 70% amino-acid sequence identity within a species. Humans possess classes I, II, III, IV and V [2] whereas the mouse is known to have expressed genes encoding ADHs of class I, II, III and IV [4,5]. Humans have three class I genes [6] encoding proteins with greater than 90% positional identity whereas the mouse has a single class I gene [7,8]. A human class V ADH with approximately 60% positional identity at the amino-acid level with the other human classes has been revealed from cDNA encoded sequence but not yet associated with an enzyme [9]. Deermouse [10] and rat [11] ADH cDNAs have been isolated that would encode proteins most closely related to this human class V with the deermouse ADH cDNA encoding a protein with 67% positional identity to this class.The ADH family of enzymes perform important metabolic functions. In the mouse, class III functions as a glutathione-dependent formaldehyde dehydrogenase 4[12] and is involved in S-nitrosoglutathione metabolism [13] and retinol metabolism (G. Duester, unpublished results). Class IV has an important role in retinol metabolism leading to retinoic acid production. Adh4 is expressed during embryogenesis [14,15] and Adh4 null mouse mutants have reduced fetal survival during vitamin A de®ciency [16]. This observation coupled with reduced conversion of retinol to retinoic acid in tissues of Adh4 mutant mice [12] suggests a role for class IV enzyme in retinoid signaling during embryogenesis. Expressed at high levels in liver, the role of class I in ethanol metabolism has been con®r...

Chlamydomonas reinhardtii is a unicellular green alga that has been used as a model organism for the study of flagella and basal bodies as well as photosynthesis. This report analyzes finished genomic DNA sequence for 0.5% of the nuclear genome. We have used three gene prediction programs as well as EST and protein homology data to estimate the total number of genes in Chlamydomonas to be between 12,000 and 16,400. Chlamydomonas appears to have many more genes than any other unicellular organism sequenced to date. Twenty-seven percent of the predicted genes have significant identity to both ESTs and to known proteins in other organisms, 32% of the predicted genes have significant identity to ESTs alone, and 14% have significant similarity to known proteins in other organisms. For gene prediction in Chlamydomonas, GreenGenie appeared to have the highest sensitivity and specificity at the exon level, scoring 71% and 82%. respectively. Two new alternative splicing events were predicted by aligning Chlamydomonas ESTs to the genomic sequence. Finally recombination differs between the two sequenced contigs. The 350-Kb of the Linkage group III contig is devoid of recombination, while the Linkage group I contig is 30 map units long over 33-kb.