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PubMed2001

Conserved synteny between the Fugu and human PTEN locus and the evolutionary conservation of vertebrate PTEN function.

Mutations of PTEN, which encodes a protein-tyrosine and lipid phosphatase, are prevalent in a variety of human cancers. The human genome 'draft' sequence still lacks organization and much of the PTEN and adjacent loci remain undefined. The pufferfish, Fugu rubripes, by virtue of having a compact genome represents an excellent template for rapid vertebrate gene discovery. Sequencing of 56 kb from the Fugu pten (fpten) locus identified four complete genes and one partial gene homologous to human genes. Genes neighboring fpten include a PAPS synthase (fpapss2) differentially expressed between non-metastatic/metastatic human carcinoma cell lines, an inositol phosphatase (fminpp1) and an omega class glutathione-S-transferase (fgsto). We have determined the order of human BAC clones at the hPTEN locus and that the locus contains hPAPSS2 and hMINPP1 genes oriented as are their Fugu orthologs. Although the human genes span 500 kb, the Fugu genes lie within only 22 kb due to the compressed intronic and intergenic regions that typify this genome. Interestingly, and providing striking evidence of regulatory element conservation between widely divergent vertebrate species, the compact 2.1 kb fpten promoter is active in human cells. Also, like hPTEN, fpten has a growth and tumor suppressor activity in human glioblastoma cells, demonstrating conservation of protein function.

Amino Acid Sequence↗
PubMed1997

Identification of functional conserved residues of CTP:glycerol-3-phosphate cytidylyltransferase. Role of histidines in the conserved HXGH in catalysis.

The CTP:glycerol-3-phosphate cytidylyltransferase (GCT) of Bacillus subtilis has been shown to be similar in primary structure to the CTP:phosphocholine cytidylyltransferases of several organisms. To identify the residues of this cytidylyltransferase family that function in catalysis, the conserved hydrophilic amino acid residues plus a conserved tryptophan of the GCT were mutated to alanine. The most dramatic losses in activity occurred with H14A and H17A; these histidine residues are part of an HXGH sequence similar to that found in class I aminoacyl-tRNA synthetases. The kcat values for H14A and H17A were decreased by factors of 5 x 10(-5) and 4 x 10(-4), respectively, with no significant change in Km values. Asp-11, which is found near the HXGH sequence in the cytidylyltransferases but not aminoacyl-tRNA synthetases, was also important for activity, with the D11A mutation decreasing activity by a factor of 2 x 10(-3). Several residues found in the sequence RTEGISTT, a signature sequence for this cytidylyltransferase family, as well as other isolated residues were also shown to be important for activity, with kcat values decreasing by factors of 0.14-4 x 10(-4). The Km values of three mutant enzymes, D38A, W74A, and D94A, for both CTP and glycerol-3-phosphate were 6-130-fold higher than that of the wild-type enzyme. Mutant enzymes were analyzed by two-dimensional NMR to determine if the overall structures of the enzymes were intact. One of the mutant enzymes, D66A, was defective in overall structure, but several of the others, including H14A and H17A, were not. These results indicate that His-14 and His-17 play a role in catalysis and suggest that their role is similar to the role of the His residues in the HXGH sequence in class I aminoacyl-tRNA synthetases, i.e. to stabilize a pentacoordinate transition state.

Amino Acid Sequence↗
PubMed1996

Evolutionary conservation of sequence and expression of the bHLH protein Atonal suggests a conserved role in neurogenesis.

atonal is a Drosophila proneural gene that belongs to the family of basic helix-loop-helix (bHLH)- containing proteins. It is expressed in the chordotonal organs and photoreceptor cells, and flies that lack Atonal protein are ataxic and blind. Here we report the cloning of atonal homologs from red flour beetle, puffer fish, chicken, mouse, and human. The bHLH domain is conserved throughout evolution, while the entire coding region is highly similar in mammals. Both the chicken and the mouse homologs are expressed early in embryogenesis in the hind brain, and specifically in cells predicted to give rise to the external granular layer of the cerebellum. In addition, these genes are expressed throughout the dorsal part of the spinal cord, in patterns different from those found for other genes, like LH-2 and wnt-1. The mouse homolog (Math1) maps to mouse chromosome 6, and the human homolog (HATH1) to human chromosome 4q22. Two neurological mouse mutants, Lc and chp, were found to map to the vicinity of Math1, but are not caused by mutations in Math1. The evolutionary conservation of this gene and its mRNA expression patterns during embryogenesis suggests that it plays a key role in the development of the vertebrate central nervous system.

Amino Acid Sequence↗
PubMed1998

Expression of wingless in the Drosophila embryo: a conserved cis-acting element lacking conserved Ci-binding sites is required for patched-mediated repression.

Patterning of the Drosophila embryo depends on the accurate expression of wingless (wg), which encodes a secreted signal required for segmentation and many other processes. Early expression of wg is regulated by the nuclear proteins of the gap and pair-rule gene classes but, after gastrulation, wg transcription is also dependent on cell-cell communication. Signaling to the Wg-producing cells is mediated by the secreted protein, Hedgehog (Hh), and by Cubitus interruptus (Ci), a transcriptional effector of the Hh signal transduction pathway. The transmembrane protein Patched (Ptc) acts as a negative regulator of wg expression; ptc- embryos have ectopic wg expression. According to the current models, Ptc is a receptor for Hh. The default activity of Ptc is to inhibit Ci function; when Ptc binds Hh, this inhibition is released and Ci can control wg transcription. We have investigated cis-acting sequences that regulate wg during the time that wg expression depends on Hh signaling. We show that approximately 4.5 kb immediately upstream of the wg transcription unit can direct expression of the reporter gene lacZ in domains similar to the normal wg pattern in the embryonic ectoderm. Expression of this reporter construct expands in ptc mutants and responds to hh activity. Within this 4.5 kb, a 150 bp element, highly conserved between D. melanogaster and Drosophila virilis, is required to spatially restrict wg transcription. Activity of this element depends on ptc, but it contains no consensus Ci-binding sites. The discovery of an element that is likely to bind a transcriptional repressor was unexpected, since the prevailing model suggests that wg expression is principally controlled by Hh signaling acting through the Ci activator. We show that wg regulatory DNA can drive lacZ in a proper wg-like pattern without any conserved Ci-binding sites and suggest that Ci can not be the sole endpoint of the Hh pathway.

Animals↗
PubMed2001

Adaptive evolutionary conservation: towards a unified concept for defining conservation units.

Recent years have seen a debate over various methods that could objectively prioritize conservation value below the species level. Most prominent among these has been the evolutionarily significant unit (ESU). We reviewed ESU concepts with the aim of proposing a more unified concept that would reconcile opposing views. Like species concepts, conflicting ESU concepts are all essentially aiming to define the same thing: segments of species whose divergence can be measured or evaluated by putting differential emphasis on the role of evolutionary forces at varied temporal scales. Thus, differences between ESU concepts lie more in the criteria used to define the ESUs themselves rather than in their fundamental essence. We provide a context-based framework for delineating ESUs which circumvents much of this situation. Rather than embroil in a befuddled debate over an optimal criterion, the key to a solution is accepting that differing criteria will work more dynamically than others and can be used alone or in combination depending on the situation. These assertions constitute the impetus behind adaptive evolutionary conservation.

Animals↗
PubMed1994

The high affinity state of the beta 2-adrenergic receptor requires unique interaction between conserved and non-conserved extracellular loop cysteines.

A disulfide bond between two extracellular cysteines, conserved in all G-protein-coupled receptors, is believed to be critical for stabilization of the ligand-binding pocket. The beta 2-adrenergic receptor (beta 2-AR) contains two conserved cysteines (Cys106 and Cys184) as well as two other extracellular cysteines (Cys190 and Cys191). The specificity of the interactions between these four cysteines has not yet been clearly established. Mutants encoding alanines for specific extracellular cysteines in the beta 2-AR gene were constructed and expressed in COS-1 and Chinese hamster ovary cells. Ala106, Ala184,190,191, and Ala106,184,190,191 mutants displayed low affinity for the beta-antagonist, 125I-cyanopindolol and insensitivity to dithiothreitol (DTT). The Ala106,191 mutant displayed an intermediate affinity and DTT sensitivity. Mutants Ala184, Ala184,190, and Ala184,191 displayed high affinity and DTT sensitivity, indicating that a solvent-accessible disulfide bond(s) is present in these mutant receptors as in the wild-type beta 2-AR. Additionally, thermal stability studies provided evidence that the extracellular disulfide bonds are essential for stabilization of the high affinity state of the receptor. These studies indicate that the covalent linkage between loops 1 and 2 of the beta 2-AR extracellular domains involves the formation of disulfide bonds, uniquely between Cys106 and Cys191, and Cys184 and Cys190, and is, thus, distinct from that of other G-protein-coupled receptors.

Amino Acid Sequence↗
PubMed1999

Local recurrence after breast conservation therapy for early stage breast carcinoma: detection, treatment, and outcome in 266 patients. Dutch Study Group on Local Recurrence after Breast Conservation (BORST).

BACKGROUND: Controversy exists concerning the roles of mammography and physical examination in the detection of local recurrence after conservation therapy for breast carcinoma. In addition, the prognostic factors for and optimal treatment of patients with local recurrence are uncertain. METHODS: At eight radiotherapy institutes, two cancer institutes, and one surgical clinic in the Netherlands, regular follow-up of patients who underwent breast conservation therapy between 1980 and 1992 identified 266 patients with local recurrence in the breast. These patients exhibited no clinical signs of distant metastases at the time of diagnosis of the local recurrence. Data on the method of detection were available for 189 patients (72%). Local recurrence was diagnosed by mammography alone in 47 cases (25%). Of all patients, 85% underwent salvage mastectomy, 8% underwent local excision, 4% received systemic treatment only, and 3% remained untreated. Specimens of the primary tumor were available for review from 238 of the 266 patients (89%). RESULTS: Local recurrences detected by mammography alone were smaller than those detected by physical examination (P = 0.04). At 5 years from the date of salvage treatment, the overall survival rate for all 266 patients was 61% (95% confidence interval [CI], 55-67%), and the distant recurrence free survival rate was 47% (95% CI, 40-53%). For the 25 patients with noninvasive recurrence, these figures were 95% and 94%, respectively. Skin involvement, the extent of recurrence (< or = 10 mm vs. >10 mm), and both lymph node status and histologic grade of the primary disease were strong predictors for distant metastases in patients with invasive recurrence. CONCLUSIONS: Patients with invasive local recurrence more than 1 cm in size are at a substantial risk for distant disease. The better distant disease free survival for patients with recurrence measuring 1 cm or less may indicate that early detection can improve the treatment outcome. Recurrence with skin involvement should be considered generalized disease.

Adult↗
PubMed1988

Sulfogalactolipid binding protein SLIP 1: a conserved function for a conserved protein.

We have studied the species and tissue expression of the 68kD sulfogalactolipid binding protein SLIP 1, originally detected in the male germ cells of the rat (Lingwood: Can. J. Biochem. Cell Biol., 63:1077-1085, 1985). Our results show that SLIP 1 has been highly conserved during evolution and is found in the testes of all vertebrates tested. In studies in the rat, we have found that SLIP 1 is, however, tissue restricted, being found only in the brain (also a major site of sulfogalactolipid biosynthesis) in addition to the testis. SLIP 1 was also detected in mammalian oocytes. The SLIP 1 species detected in brain and oocytes retain the sulfogalactolipid-binding characteristics of rat testicular SLIP 1, indicating that, in addition to immunological features, the glycolipid-binding function of SLIP 1 is conserved in these tissues.

Animals↗
PubMed1994

Methylation of the conserved A1518-A1519 in Escherichia coli 16S ribosomal RNA by the ksgA methyltransferase is influenced by methylations around the similarly conserved U1512.G1523 base pair in the 3' terminal hairpin.

An in vitro system developed for the site-specific mutagenesis of 16S rRNA of Escherichia coli ribosomes was used to make five mutations around the highly conserved U1512.G1523 base pair in the 3' terminal hairpin. Each of the mutant RNAs was reconstituted with a complete mixture of 30S proteins to yield 30S ribosomal particles, which were tested for the ability of the ksgA methylase to form m6(2)A1518 and m6(2)A1519. Dimethylation of A1518 and A1519 in the hairpin loop was inhibited 20-80% by the mutations. The results indicate that G1523 and C1524 in the stem are important determinants for the dimethylation of A1518 and A1519 in the loop. Either the enzyme recognition region extends that far or the effect of mutations in the stem are propagated in some manner to the loop. The conserved U.G base pair does not of itself appear to play a major role in ksgA methylase recognition.

Base Composition↗
PubMed1994

Conservation of the human breast basic conserved 1 gene in the plant kingdom: characterization of a cDNA clone from Arabidopsis thaliana.

Based on low-stringency genomic Southern analysis, the recently described human breast basic conserved 1 (BBC1) gene has been proposed to be conserved throughout Eukaryota [Adams et al., Hum. Mol. Genet. 1 (1992) 91-96]. We have isolated and characterized a cDNA clone (AtBBC1) which corresponds to a BBC1 homologue from the model plant species, Arabidopsis thaliana. Furthermore, upon Northern analysis, the AtBBC1 probe detects related transcripts in various dicotyledenous and monocotyledonous plant species, indicating that actively transcribed BBC1-related genes are widespread in the plant kingdom. BBC1 has been shown to be expressed in all mammalian tissues examined [Adams et al., Hum. Mol. Genet. 1 (1992) 91-96]; similarly, here the AtBBC1 transcript has been detected in a variety of A. thaliana organs. In addition, the abundance of the AtBBC1 mRNA is developmentally regulated during the course of fruit maturation, and is positively correlated with active cell division.

Amino Acid Sequence↗
PubMed2005

Ipsilateral breast tumor recurrence after breast conservation therapy: outcomes of salvage mastectomy vs. salvage breast-conserving surgery and prognostic factors for salvage breast preservation.

PURPOSE: To compare outcomes of salvage mastectomy (SM) and salvage breast-conserving surgery (SBCS) and study the feasibility of SBCS. METHODS AND MATERIALS: Of 2,038 patients treated with breast-conserving therapy at Yale-New Haven Hospital before 1999, 166 sustained an ipsilateral breast tumor recurrence (IBTR). Outcomes and prognostic factors of patients treated with SM or SBCS were compared. Patients were considered amenable to SBCS if the recurrence was localized on mammogram and physical examination, and had pathologic size < 3 cm, confined to the biopsy site, without skin or lymphovascular invasion, and with < or = 3 positive nodes. RESULTS: Of the 146 patients definitively managed at IBTR, surgery was SM (n = 116) or SBCS (n = 30). The median length of follow-up after IBTR was 13.8 years. The SM and SBCS cohorts had no significant differences, except at IBTR the SM cohort had a greater tumor size (p = 0.049). Of the SM cohort, 65.5% were considered appropriate for SBCS, and a localized relapse was predicted by estrogen-receptor positive, diploid, and detection of recurrence by mammogram. Multicentric disease correlated with BRCA1/2 mutation, estrogen-receptor negative, lymph node positive at relapse, and detection of recurrence by physical examination. Survival after IBTR was 64.5% at 10 years, with no significant difference between SM (65.7%) and SBCS (58.0%). Only 2 patients in the SBCS cohort subsequently had a second IBTR, and were salvaged with mastectomy. CONCLUSIONS: While mastectomy is considered the standard surgical salvage of IBTR, SBCS is feasible and prognostic factors are related to favorable tumor biology and early detection. Patients with BRCA1/2 germline mutations may be less appropriate for SBCS, as multicentric disease was more prevalent. Patients who underwent SBCS had comparable outcomes as those who underwent SM, but remain at continued risk for IBTR. A prospective trial evaluating repeat lumpectomy and partial breast reirradiation is discussed.

Adult↗
PubMed2000

The 1993-94 patterns of care process survey for breast irradiation after breast-conserving surgery-comparison with the 1992 standard for breast conservation treatment. The Patterns of Care Study, American College of Radiology.

PURPOSE: To determine the patterns of evaluation and treatment in the U.S. of women with early breast cancer treated with breast-conserving surgery and irradiation in 1993-94, and to compare these with a similar survey in 1983 and with the 1992 Standard for Breast Conservation Treatment. METHODS AND MATERIALS: In 1995-96, 727 randomly selected records of eligible patients treated from 1993-94 at 62 facilities representative of 3 practice types were reviewed. RESULTS: Compared with the Process Survey (PS) in 1983, patients in the 1993-94 study had an older age distribution. In the current study, 70% of patients were > or = 50 years of age, and 69% were post-menopausal, compared with 59% > or = 50 years of age and 49% post-menopausal in 1983 (p = 0.0087 and < 0.001, respectively). Work-up and evaluation in the 1993-94 PS were closely aligned with the standard and were considerably improved compared with 1983. In the 1983 study, 77% of patients underwent mammography, as compared to 97% in the 1993-94 study. In 1983, pathological size documentation was performed in 83% of patients; in 1993-94, this was performed in 95% of patients. An estrogen receptor evaluation was performed in 36% of patients in 1983; in 1993-94, that increased to 76%. In 1983, 28% of patients underwent progesterone receptor evaluation; in 1993-94, this increased to 72%. Only 3% of patients in 1993-94 were enrolled in a clinical trial. Radiation treatment parameters closely adhered to standard recommendations, improving substantially from 1983. In 1983, wedge or compensator use was recommended for 64% of patients; in 1993-94, for 95% of patients. In 1983, 4-8 MV photons were recommended for breast treatment in 67% of patients; in 1993-94, 90%. In 1983, bolus was avoided in 75% of patients; in 1993-94, in 94%. In 1983, the recommended breast dose for 89% of patients was 45-50 Gy (44-51 Gy in PS); in 1993-94 this had increased to 99% of patients. In 1983, electrons were recommended for primary site boost in 70% of patients; in 1993-94, for 94% of patients. CONCLUSION: There was an extensive shift to adherence to the 1992 standard in 1993-94, compared with the 1983 PS, although there is room for improvement in some areas.

Adult↗
PubMed1999

Histological determinants for different types of local recurrence after breast-conserving therapy of invasive breast cancer. Dutch Study Group on local Recurrence after Breast Conservation (BORST)

The purpose of this study was to determine which histological factors are associated with an increased risk for local recurrence in the breast after breast-conserving therapy for early breast cancer (TNM stage I and II) and whether risk patterns vary according to menopausal status and type of local recurrence. Through complete follow-up of the patients of eight regional radiation oncology departments, two cancer institutes and one surgical clinic in The Netherlands, 360 patients were identified with local recurrence in the breast after having received breast-conserving therapy (local tumour excision, axillary dissection and irradiation of the whole breast and a boost to the tumour bed) during the 1980s. For each case, two controls with a follow-up of similar duration without local recurrence were randomly selected. Histological slides of the primary tumour were reviewed. Among premenopausal patients the risk of recurrence for those younger than 35 years was significantly higher than that for premenopausal patients of 45 years or older (relative risk (RR) 2.9; 95% confidence interval (95% CI) 1.3-6.6, P < 0.05). The risk of recurrence at or near the site of the primary tumour was most significantly increased for patients with high grade extensive intraductal component (EIC) adjacent to the primary tumour (RR 4.1; 95% CI 1.7-9.8, P < 0.01). Microscopic margin involvement was an important risk indicator for diffuse recurrence and recurrence in the skin of the breast, especially in the presence of vascular invasion (RR 25; 95% CI 4.0-150, P < 0.001). To prevent local recurrence at or near the site of the primary tumour, local excision with a 1-2 cm margin of healthy tissue and a 15 Gy boost seemed adequate local treatment for patients with well differentiated EIC. In contrast, a wider surgical margin, a higher boost dose or mastectomy should be considered for patients with poorly differentiated EIC. Microscopic margin involvement in the presence of vascular invasion significantly increases the risk of diffuse recurrence or recurrence in the skin.

Adult↗
PubMed1997

Site-directed mutagenesis of either the highly conserved Trp-22 or the moderately conserved Trp-95 to a large, hydrophobic residue reduces the thermodynamic stability of a spectrin repeating unit.

As reported previously (MacDonald, R. I., Musacchio, A., Holmgren, R. A., and Saraste, M. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 1299-1303), an unfolded peptide was obtained by site-directed mutagenesis of Trp-22 to Ala in the cloned, wild type 17th repeating unit (alpha17) of chicken brain alpha-spectrin. Trp occurs in position 22 of nearly all repeating units of spectrin. In the present study, Trp-22 was mutated to Phe or to Tyr to compare thermodynamic stabilities of urea-induced unfolding of alpha16 and mutants thereof. alpha16 was chosen for this study instead of alpha17, because alpha16 has two tryptophans, allowing urea-induced unfolding to be tracked by the fluorescence of the Trp remaining in each mutant peptide and by circular dichroism in the far UV. The free energies of unfolding of W22Y and W22F were 50% that of alpha16, showing that Trp-22 is crucial in stabilizing the triple helical bundle motif of the spectrin repeating unit. Mutation of the moderately conserved Trp-95 of alpha16 to Val, which occupies position 95 in alpha17, also yielded a peptide with 50% of the free energy of unfolding of alpha16. Thus, the thermodynamic stability of a given spectrin repeating unit may depend on both moderately and highly conserved tryptophans. Different structural roles of Trp-22 and Trp-95 in alpha16 are suggested by the slightly higher wavelength of maximum emission of Trp-22, the greater acrylamide quenching of Trp-95 than Trp-22, and the longer lifetime of Trp-95. For comparison with alpha16, urea-induced unfolding of spectrin dimer isolated from human red cells was monitored by far UV-CD and by tryptophan fluorescence. Thermodynamic parameters could not be rigorously derived for the stability of spectrin dimer because unfolding of spectrin dimer involved more than two states, unlike unfolding of cloned repeating units. However, the similar midpoints of CD-monitored denaturation curves of alpha16 and spectrin dimer, i. e. 2.7 and 3.2 M urea, respectively, indicate that investigation of cloned repeating units of spectrin can provide physiologically relevant information on these structures.

Amino Acid Sequence↗
PubMed1986

Functional, developmentally expressed genes for mouse U1a and U1b snRNAs contain both conserved and non-conserved transcription signals.

Four genes that encode mouse U1a1, U1b2 and U1b6 snRNAs have been isolated from a mouse genomic DNA library. They all appear to be functional U1 genes since they are accurately transcribed into full length, capped snRNAs upon injection into Xenopus oocytes. A mouse pseudogene that is not transcribed in Xenopus oocytes was also isolated from the mouse genomic library. DNA sequence analysis of the 5' and 3' flanking regions of the functional genes revealed the presence of three highly conserved sequence elements that have been shown to be required for transcription initiation or 3' end formation in other U1 genes. Each of these U1 RNA genes also contains non-conserved sequences in the 5' flanking region that could function in their controlled expression during development.

Animals↗
PubMed1988

The preference of the mitochondrial endonuclease for a conserved sequence block in mitochondrial DNA is highly conserved during mammalian evolution.

Endonuclease activity identified in crude preparations of rat and human heart mitochondria has each been partially purified and characterized. Both the rat and human activities purify as a single enzyme that closely resembles the endonuclease of bovine-heart mitochondria (Cummings, O.W. et. al. (1987) J. Biol. Chem. 262:2005-2015). All three enzymes, for example elute similarly during gel filtration and DNA-cellulose chromatography, and exhibit similar enzymatic properties. Although the nucleotide sequences of the mtDNAs indicate that there has occurred an unusual degree of divergence in the displacement-loop region during mammalian evolution, the nucleotide specificities of the mt endonucleases appear highly conserved and show a striking preference for an evolutionarily-conserved sequence tract that is located upstream from the heavy (H)-strand origin of DNA replication (OriH).

Animals↗
PubMed2006

Evolutionarily conserved and non-conserved retrovirus restriction activities of artiodactyl APOBEC3F proteins.

The APOBEC3 proteins are unique to mammals. Many inhibit retrovirus infection through a cDNA cytosine deamination mechanism. HIV-1 neutralizes this host defense through Vif, which triggers APOBEC3 ubiquitination and degradation. Here, we report an APOBEC3F-like, double deaminase domain protein from three artiodactyls: cattle, pigs and sheep. Like their human counterparts, APOBEC3F and APOBEC3G, the artiodactyl APOBEC3F proteins are DNA cytosine deaminases that locate predominantly to the cytosol and can inhibit the replication of HIV-1 and MLV. Retrovirus restriction is attributable to deaminase-dependent and -independent mechanisms, as deaminase-defective mutants retain significant anti-retroviral activity. However, unlike human APOBEC3F and APOBEC3G, the artiodactyl APOBEC3F proteins have an active N-terminal DNA cytosine deaminase domain, which elicits a broader dinucleotide deamination preference, and they are resistant to HIV-1 Vif. These data indicate that DNA cytosine deamination; sub-cellular localization and retrovirus restriction activities are conserved in mammals, whereas active site location, local mutational preferences and Vif susceptibility are not. Together, these studies indicate that some properties of the mammal-specific, APOBEC3-dependent retroelement restriction system are necessary and conserved, but others are simultaneously modular and highly adaptable.

Amino Acid Sequence↗
PubMed1991

Mapping of the gene for a major penicillin-binding protein to a genetically conserved region of the Bacillus subtilis chromosome and conservation of the protein among related species of Bacillus.

Penicillin-binding protein 5 is the most abundant penicillin-binding protein in the vegetative membranes of Bacillus subtilis and accounts for 95% of the D,D-carboxypeptidase activity of the cell. The structural gene for penicillin-binding protein 5 was mapped to a genetically conserved region near guaB at 0 degrees on the B. subtilis chromosome, and immunoassays revealed that there is conservation of this major penicillin-binding protein among related species.

Bacillus↗