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PubMed1995

Molecular analysis of the endosymbionts of tsetse flies: 16S rDNA locus and over-expression of a chaperonin.

Based on 16S rDNA sequence comparison, intracellular mycetome-associated endosymbionts (P-endosymbionts) of tsetse flies (Diptera: Glossinidae) form a distinct lineage within the gamma-3 subdivision of proteobacteria, related to the free-living bacterium Escherichia coli, midgut S-endosymbionts of various insects including tsetse flies, and to the P-endosymbiont lineage of aphids, Buchnera aphidicola. Gene organization and expression of several loci in intracellular microorganisms have revealed differences from free-living bacteria. This study analyses two of these characteristics in tsetse endosymbionts; the copy number and gene organization of rDNA operations and the nature of the abundant protein(s) synthesized by these microorganisms. Results indicate that Glossina morsitans morsitans S-endosymbionts have multiple (seven) rDNA operons coding for 16S (rrs) followed by 23S (rrl) gene sequences, whereas tsetse P-endosymbionts have a single, similarly organized rDNA operon. In tsetse mycetocytes in vitro, P-endosymbionts synthesize a predominant protein of 60 kDa in size (p60) which by Western blot analysis shows immunological cross-reactivity with the abundant 63 kDa (p63) protein of B. aphidicola. p63 (also referred to as symbionin) has been characterized as a molecular chaperone, structurally and functionally similar to the groEL protein of E. coli. Under in vitro conditions, tsetse S-endosymbionts synthesize high levels of a similarly-sized protein that cross-reacts with p63 chaperonin. Antisera against the tsetse p60 protein also recognizes p63 protein of B. aphidicola, suggesting that the abundant tsetse endosymbiont protein is a chaperonin.

Animals↗
PubMed1985

Operator mutations of the Escherichia coli aroF gene.

The Escherichia coli aroF and aroG genes encode the tyrosine-sensitive and the phenylalanine-sensitive 3-deoxy-D-arabino-heptulosonate 7-phosphate synthases, respectively, two of the three isoenzymes that control carbon flow through the shikimate pathway. Transcription of aroF and aroG is repressed by the tyrR gene product complexed to tyrosine or phenylalanine, respectively. Constitutive aroF mutants with lesions linked to aroF were isolated. The nucleotide sequences in the regulatory regions of aroF from six such mutants and from the parental wild type strain were determined. The mutations were found in two 18-base pair imperfect palindromes, called aroFo1 and aroFo2, which are located upstream of the aroF transcription start by 61 and 113 base pairs, respectively. Nuclease S1 mapping and analysis of in vitro run-off transcripts identified the 5'-end of the aroF transcript 51 base pairs upstream of the aroF translation start. The -35 region of the aroF promoter overlaps aroFo1. The aroFo1 and aroFo2 sequences are homologous to a single 18-base pair DNA segment preceding the coding sequence of aroG.

3-Deoxy-7-Phosphoheptulonate Synthase↗
PubMed1989

Differential regulation of soybean chalcone synthase genes in plant defence, symbiosis and upon environmental stimuli.

Four independent recombinant lambda clones hybridizing to parsley chalcone synthase (CHS) cDNA were isolated from a soybean (Glycine max) genomic library. Restriction fragment length polymorphism (RFLP) analysis indicated that the CHS gene family comprises six members. The CHS genes were found to be clustered with three genes on a 10 kb segment and pairs on others. DNA sequences of the 5'-, the coding-, and the 3' untranslated regions were determined for three different genes. A consensus alignment of the 5' regions revealed extensive homology between them for up to 150 bp upstream of the TATA box. Developmental regulation of CHS was observed in uninfected and in rhizobium-infected roots. Regulation at the level of transcription by different stimuli was investigated in the root, stem and cotyledons of soybean seedlings. Our results suggest a co-operative induction of CHS genes by wounding and elicitor treatment of cotyledons. The most rapid transcript accumulation, however, was observed in roots and stems. The induction of CHS genes by light was found to be UV dependent. A possible involvement of different members of the CHS gene family in response to elicitor versus UV treatment was analysed by the use of gene specific probes, and unexpectedly revealed that only CHS 1 transcription was induced by either elicitor or UV treatment of seedlings.

Acyltransferases↗
PubMed1988

Operator constitutive mutation of 3-hydroxy-3-methylglutaryl coenzyme A reductase promoter abolishes protein binding to sterol regulatory element.

Through substitution mutagenesis we identified the promoter elements responsible for basal expression and sterol-mediated repression of transcription of the gene for 3-hydroxy-3-methylglutaryl coenzyme A reductase, a rate-controlling enzyme of cholesterol biosynthesis. Mutant promoters containing 277 base pairs (bp) of reductase 5' flanking sequence were inserted into recombinant plasmids upstream of the coding region for bacterial chloramphenicol acetyltransferase. The plasmids were transfected into hamster fibroblasts, and transcription was measured in the presence and absence of sterols. Mutations in three regions that are known to bind nuclear proteins markedly reduced transcription. Mutation of another protein-binding region of 20 bp in length did not reduce transcription, but it did abolish sterol-mediated repression, producing an operator constitutive phenotype. This mutation also abolished protein binding to the corresponding 20-bp region of DNA as determined by footprinting assays. When a DNA fragment containing these 20 bp was inserted into the herpes simplex virus thymidine kinase promoter, sterol-mediated repression was observed. This sequence contains an octanucleotide that shows a 7/8-bp match with a previously identified regulatory sequence in repeat 2 of the low density lipoprotein receptor promoter, another sterol-repressible gene. We hypothesize that this octanucleotide, GTGGCGGTG, is the core binding site for a sterol-dependent protein that represses transcription.

Animals↗
PubMed1990

Selective IgG deficiency with a transcriptional disorder of the gamma switching region gene and the IL-4 gene.

A primary immunodeficiency patient was analysed whose serum IgG and IgE were extremely low but whose IgM and IgA levels were within the normal range or elevated. Southern blot analysis indicated no deletion of structural genes coding for C gamma, C epsilon, or C alpha. The majority of the patient's peripheral B cells expressed IgM and IgD on the surface yet IgG-positive B cells were not detected, suggesting that the defect is in a switch-recombination process from IgM to IgG. The RFLP pattern detected with the S mu and S gamma DNA regions revealed that there was no deletion or large mutation in the switch region DNA. An in vitro IgG production system with pokeweed mitogen showed an abnormality at the transcriptional level and the defects were in both the patient's T and B cells. Addition of recombinant IL-4 (rIL-4) to the normal B cells enhanced IgG production but the patient's B cells did not respond to rIL-4, although the IL-4 receptor was present at the normal level. Messenger RNA and IL-4 protein were not produced in the patient's T cells upon stimulation with phorbol ester and calcium ionophore, whereas IL-2 was normally produced. The patient's lymphocytes showed a proliferative response to various mitogens, including phorbol ester. The transcripts of unrearranged C gamma region genes were not detected in the patient's lymphocytes, suggesting that the chromatin structure of the S gamma region may not be open. These results suggest that the transcriptional defects at the S gamma region gene in B cells and at the IL-4 gene in the T cells may be responsible for the present IgG immunodeficiency. There might be a common transcriptional system operating in a certain step in the activation of both genes.

Adult↗
PubMed1987

Transcriptional control in the EcoRI-F immunity region of Bacillus subtilis phage phi 105. Identification and unusual structure of the operator.

We present the first evidence, in Bacillus subtilis, for gene regulation through the classical mechanism of repressor-operator interaction. The EcoRI-F immunity region (immF) of lysogenic phage phi 105 contains two promoters, PM and PR, in divergent orientations. PM initiates transcription of the phi 105 repressor (c phi 105) gene, whereas PR most probably signals the onset of the lytic pathway. Fusions between each of these promoters and the cat-86 gene were constructed, and in-vivo promoter activities were determined, in both the presence and absence of the functional c phi 105 product, using S1 nuclease analysis and chloramphenicol acetyl transferase assays. The results showed that transcription from PM is stimulated, whereas PR activity is negatively controlled by the repressor. This differential regulation appears to be mediated by recognition of a 14 base-pair (bp) sequence, 5' GACGGAAATACAAG 3', three identical copies of which are present as direct repeats. Two copies, OR1 and OR2, are located closely together in the non-transcribed region between PM and PR, but do not overlap with the -35 and -10 regions of these promoters. The third copy, OR3, is located some 250 bp downstream from PR, within the coding region (ORF3) of the proximal gene of the PR transcription unit. When a 231 bp restriction fragment containing only OR3 was inserted between a strong constitutive promoter (P138) and the cat-86 gene, the in-vivo expression of chloramphenicol resistance was considerably reduced in the presence, but not in the absence, of phi 105 repressor. This hybrid P138-OR-cat-86 construct was subsequently used to select in vivo for operator-constitutive (Oc) mutations. Of 25 Oc mutants analyzed, all showed base alterations or deletions affecting the 14 bp sequence. We show further that insertion of a chemically synthesized oligonucleotide, containing the 14 bp OR sequence, at a site more than 100 bp downstream from the constitutive P138 is sufficient for transcription to become negatively controlled by phi 105 repressor. In comparison with previously identified Gram-negative bacterial and phage operators, the most unusual aspect of the phi 105 OR sequence appears to be its complete lack of 2-fold rotational symmetry.

Bacillus subtilis↗
PubMed1991

Effects of unilateral cortex lesions on gene expression of rat cortical cholecystokinin neurons.

In rat neocortex, the gene encoding preprocholecystokinin is expressed in interneurons which also synthetize gamma-aminobutyric acid. An injury to the meninges and the underlying cortex increased the concentration of mRNA coding for preprocholecystokinin in all ipsilateral cortical areas. Simultaneous treatment of the rats with the anti-inflammatory agent diclofenac did not affect the injury-induced change in gene expression indicating that inflammatory processes were not involved. The injury also enhanced the expression of the immediate early gene c-fos in the ipsilateral cortex in a time-dependent manner. There was an increase in c-fos mRNA 1 h after the operation, which was no longer observed 3 h later. Twenty-four hours after the operation, cells containing c-fos mRNA were found in cortical layers II, III, V and VI. The neurons which showed an increased expression of preprocholecystokinin were also in these layers. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 prevented the injury-induced increases in both preprocholecystokinin and c-fos gene expression, indicating that stimulation of this glutamate receptor subtype may initiate the changes in expression of both genes. It is hypothetized that the immediate early gene c-fos is activated first and this then leads to the increase in preprocholecystokinin mRNA.

Animals↗
PubMed1989

Gene expression in regenerating liver in relation to cell proliferation and stress.

When hepatocyte proliferation is stimulated in the liver by partial hepatectomy, messenger RNAs coding for fibrinogen, actin, c-myc and topoisomerase I are rapidly accumulated. We distinguish an early phase of accumulation (0-3 h after partial hepatectomy) which is also observed after a sham operation for the four genes, and during inflammation produced by Freund's adjuvant in the case of fibrinogen and c-myc genes. The hepatic response to inflammation appears therefore to mimic events characteristic of the G0/G1 transition, such as the accumulation of the c-myc mRNA. The late phase of mRNA accumulation (beyond 3 h after partial hepatectomy) is typical of liver regeneration. The level of c-myc mRNA is transiently increased (20-fold over normal) 20 h after partial hepatectomy, that is, at the time of DNA synthesis. Topoisomerase-I mRNA level increases between 3 and 24 h after partial hepatectomy (5-10-fold over normal). These results suggest that accumulation of c-myc and topoisomerase-I mRNAs is associated with DNA replication in regenerating liver.

Actins↗
PubMed1990

The Balbiani ring 3 gene in Chironomus tentans has a diverged repetitive structure split by many introns.

A set of approximately 15 secretory proteins is synthesized by the salivary gland cells in the midge Chironomus tentans. These proteins are secreted but do not form insoluble fibers until they are transported out of the gland lumen. A Balbiani ring (BR) gene family consisting of four genes (BR1, BR2.1, BR2.2 and BR6) have previously been shown to encode four of these proteins, sp-I a to d, with relative molecular weights of 1 x 10(6). Each BR gene contains an uninterrupted block in which about 100 repeats are tandemly arranged. The repeats are virtually identical and efficient homogenization mechanisms must operate within each block. Here we describe a new BR gene, the BR3 gene, which according to structural similarities may belong to the BR gene family, but at the same time exhibits a strikingly different structure. The gene encodes a 10.9 kb transcript that contains 38 introns and is spliced into a 5.5 kb mRNA. The mRNA is translated into a cysteine-rich 185 kDa major component of the gland secretion. The coding sequence in the gene is built from diverged repeats in which mainly the cysteine codons are preserved and the sequence is split by the introns into 17 to 678-bp long exons. The introns are located at defined positions in relation to the repeat structure. In sharp contrast to the uninterrupted array of identical repeats in the BR1-BR6 genes, the repeats in the BR3 gene are not efficiently homogenized and have diverged extensively from each other. We propose that the splitting of the repeat structure into variable sized exons prevents homogenizations dependent on unequal aligning of homologous sequences.

Amino Acid Sequence↗
PubMed1991

Targeting the Escherichia coli lac repressor to the mammalian cell nucleus.

We have previously shown that about 90% of total Escherichia coli lac repressor synthesized in mammalian cells is located in the cytoplasm [Hu and Davidson, Cell 48 (1987) 555-566]. To target a functional lac repressor to the nucleus, we mutated 10 nucleotides at the 3' end of the coding sequence, thus adding the nuclear localization signal of the simian virus 40 large-T antigen to the C terminus of the repressor. The mutant lacI gene and the wild-type (wt) gene, both in standard animal cell expression vectors, driven by the promoter of the Rous sarcoma virus long terminal repeat, were stably transfected into three rodent cell lines. In confirmation of our previous results, only about 10% of the wt repressor, but all of the mutant protein, was localized in the nucleus. DNase I footprint analyses showed that the mutant repressor retained the same operator DNA-binding specificity as wt repressor. Furthermore, both repressor-operator complexes could be dissociated by addition of isopropyl-beta-D-thiogalactopyranoside in vitro. However, the ratio of number of repressor molecules per nucleus that, by in vitro assay, could bind to the operator sequence to the number of monomer repressor polypeptides per nucleus, as determined by Western blotting, was about 1:4 for the wt repressor and about 1:30 for the mutant repressor. This suggests that: (a) the mutant repressor assembles into tetramers inefficiently; and/or (b) it has reduced binding affinity to the operator sequence; and/or (c) it has higher binding affinity to nonspecific DNA.

Antigens, Viral, Tumor↗
PubMed1990

Frequent activation of N-myc genes by hepadnavirus insertion in woodchuck liver tumours.

The recent finding of c-myc activation by insertion of woodchuck hepatitis virus DNA in two independent hepatocellular carcinoma has given support to the hypothesis that integration of hepatitis B viruses into the host genome, observed in most human and woodchuck liver tumours, might contribute to oncogenesis. We report here high frequency of woodchuck hepatitis virus DNA integrations in two newly identified N-myc genes: N-myc1, the homologue of known mammalian N-myc genes, and N-myc2, an intronless 'complementary DNA gene' or 'retroposon' that has retained extensive coding and transforming homology with N-myc. N-myc2 is totally silent in normal liver, but is overexpressed without genetic rearrangements in most liver tumours. Moreover, viral integrations occur within either N-myc1 or N-myc2 in about 20% of the tumours, giving rise to chimaeric messenger RNAs in which the 3' untranslated region of N-myc was replaced by woodchuck hepatitis virus sequences encompassing the viral enhancer. Insertion sites were clustered in a short sequence of the third exon that coincides with a retroviral integration hotspot within the murine N-myc gene, recently described in T-cell lymphomas induced by murine leukaemia virus. Thus, comparable mechanisms, leading to deregulated expression of N-myc genes, may operate in the development of tumours induced either by hepatitis virus or by nonacute retroviruses in rodents. Activation of myc genes by insertion of hepadnavirus DNA now emerges as a common event in the genesis of woodchuck hepatocellular carcinoma.

Amino Acid Sequence↗
PubMed1992

Cardiac hypertrophy-induced changes in mRNA levels for TGF-beta 1, fibronectin, and collagen.

Cardiac hypertrophy induced by pressure overload is accompanied by increases in the deposition of extracellular matrix (ECM) proteins. We wanted to determine in this study whether changes in mRNA coding for transforming growth factor (TGF)-beta 1, TGF-beta 3, and the ECM proteins, fibronectin and collagen, occur during the early phases of cardiac hypertrophy. Steady-state mRNA levels were determined in sham-operated and thoracic-banded hypertrophied rat myocardium from 6 h to 30 days after surgery. TGF-beta 1 mRNA increased significantly (1.7-fold vs. control) 12 h after aortic banding, decreasing to control levels by 14 days. No significant changes were observed for TGF-beta 3 message. Fibronectin mRNA levels increased twofold at day 1 and peaked to approximately threefold at day 3. Type I and III collagen mRNA expression was similar to control levels at day 1 but increased significantly 3 days after banding. Cardiac hypertrophy also resulted in an induction of mRNA for an embryonic isoform of fibronectin (EIIIA+) that is generated through alternative splicing of the gene. These findings indicate that, with myocardial hypertrophy, mRNAs for fibronectin are increased as early as 1 day after banding, which may allow for an initial increase in the production of fibronectin followed by the deposition of collagen. These increased mRNA levels for the ECM proteins are preceded by marked increases in TGF-beta 1 mRNAs.

Animals↗
PubMed1991

Colocalization of neurotransmitters analyzed by in situ hybridization.

In situ hybridization and Northern blot analysis has been used to analyse in some detail the localization and regulation of the messenger molecules adrenaline, noradrenaline and neuropeptide tyrosine (NPY) within cells of the sympathetic nervous system and the adrenal medulla. In the rat adrenal gland, a novel NPY containing population of ganglion cells was found. Synthetic oligonucleotide probes complementary to mRNA coding for the catecholamine synthesizing enzymes phenylethanolamine N-methyltransferase (PNMT), tyrosine hydroxylase (TH) and NPY were used to analyse the regulation of these genes following administration of the catecholamine depleting drug reserpine. Twenty-four hours after a single dose of reserpine, a differential regulation of PNMT, TH and NPY was found. Thus, a dramatic decrease in PNMT mRNA was observed in the adrenal medulla. In contrast, mRNA for both TH and NPY exhibited an increase. Different regulatory mechanisms may thus operate for these three compounds coexisting in chromaffin cells of the adrenal medulla. The regulation of enzymes and peptides was also studied in human sympathetic ganglia. After brief electrical preganglionic stimulation of thoracic ganglia in humans, in situ hybridization was performed with synthetic oligonucleotide probes complementary to TH, dopamine beta-hydroxylase (DBH) and NPY mRNA respectively. A several fold increase in all three mRNAs was found in the principal ganglion cells. The results point to a very rapid regulation of genes involved in signal transmission in the sympathetic nervous system of humans. The results also suggest a novel way to define neuronal projections by visualizing increases in mRNA levels following electrical stimulation.

Adrenal Glands↗
PubMed1988

Search for a scrapie-specific nucleic acid: a progress report.

Scrapie agent contains a proteinaceous component as well as an 'informational' molecule (suggested by the existence of distinct strains of scrapie). These operationally defined entities may be the same molecule, an infectious protein, or distinct, in which case a nucleic acid might encode the genetic information. Purification of scrapie agent enriched a protein, PrPSc, by virtue of its relative protease resistance. There is only a single PrP gene and the primary translation product of PrP mRNA is the same in normal and scrapie-infected brain; therefore the normal PrPC and the protease-resistant isoform, PrPSc, found in scrapie, probably result from different post-translational events. To search for scrapie-specific nucleic acid, globin RNA made in vitro was added to highly purified infectious preparations at a ratio of 10(3) molecules per infectious unit, nucleic acids were isolated and denatured, and cDNA synthesized using random oligonucleotide primers. Clones containing globin-related sequences were identified by in situ hybridization. 150 plaques not hybridizing to the globin probe were isolated. Inserts larger than 50 base pairs were analysed. By hybridization to a globin probe at reduced stringency all but four clones were found to contain small globin related inserts; two of these hybridized to hamster repetitive sequences as shown by Southern blot analysis. The other clones not related to hamster nucleic acids may be derived from unknown sources of contamination or from scrapie-specific nucleic acids.

Animals↗
PubMed1989

[Left ventricular accumulation of messenger ribonucleic acid coding for the natriuretic atrial factor in various experimental models of cardiac hypertrophy in rats].

Cardiac hypertrophy secondary to chronic hemodynamic overload is associated with an increase in the ventricular concentration of the messenger ribonucleic acid (mRNA) coding for the atrial natriuretic factor (ANF). We have compared, in male Wistar rats (10 week old, 200-220 g), using dot blot hybridization and a specific oligonucleotide probe, the left ventricular concentration of ANF mRNA (LV ANF mRNA) in 4 models of chronic hemodynamic overload inducing various patterns of left ventricular hypertrophy (LVH): a model of volume overload, the aortocaval fistula (ACF, n = 15); a model of pressure overload, coarctation of the abdominal aorta (CoA, n = 13) and 2 models of mixed overload, aortic regurgitation (AR, n = 7) and myocardial infarction (INF, n = 18). A month after surgery, LVH was 49 p. 100 for AR, 41 p. 100 for Co A and 21 p. 100 for ACF. Instead of a severe infarction, LVH was 6 p. 100 in INF demonstrating a marked hypertrophy of the non infarcted myocardium. For each model, LV ANF mRNA was compared to that in a corresponding group of sham-operated control rats and expressed as the percentage of ANF mRNA concentration in the pooled atria of the controls. In the 4 control groups LV ANF mRNA was 1 +/- 0.5 p. 100 that in the corresponding atria and the sham-operated animals were thus pooled in a single group (n = 19). In the 4 models of LVH, LV ANF mRNA markedly increased as compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Genetic definition of the translational operator of the threonine-tRNA ligase gene in Escherichia coli.

The Escherichia coli gene thrS that codes for threonine-tRNA ligase (tRNAThr ligase, formerly threonine-tRNA synthetase, EC 6.1.1.3) has previously been shown to be negatively autoregulated at the level of translation. Here we describe the use of several thrS-lac gene fusions to isolate cis-acting regulatory mutations that increase the translation but not the transcription of the thrS gene. These mutations lead to a total loss of control of repression and derepression of thrS. DNA sequence analysis locates the mutations between 10 and 40 base pairs upstream of the translation initiation codon of thrS and more than 100 base pairs downstream of the transcription initiation site. The mRNA region where these mutations are located shares primary and secondary structure homologies with specific parts of several isoacceptor tRNAThr species. These findings suggest that the ligase regulates its translation by binding to its mRNA at a place that shares some homology with its natural substrate.

Amino Acyl-tRNA Synthetases↗
PubMed1990

Changes in messenger RNAs coding for neurotransmitter receptors and voltage-operated channels in the developing rat cerebral cortex.

The ontogenetic development of poly(A)+ mRNAs coding for receptors to several neurotransmitters (kainate, glutamate, acetylcholine, and serotonin) and voltage-operated channels (sodium and calcium) was studied by isolating total poly(A)+ mRNA from the brains of rats at various developmental stages and injecting it into Xenopus oocytes. The oocytes translated the foreign mRNA and incorporated functional receptor/ion channel complexes into the cell membrane. Thus, recording of induced membrane currents in voltage-clamped oocytes gave a measure of the relative amounts of the different messengers. Responses induced by kainate, glutamate, acetylcholine, and serotonin all increased with age and reached a maximum in oocytes injected with mRNA from adult cortex. Messenger RNAs for the earliest ages examined, Embryonic Days 15 and 18, expressed little or no response to kainate, glutamate, or acetylcholine, while 50-70% of the adult response was reached by Postnatal Day 10. In contrast, the serotonin-induced response was already comparatively large (16% of the adult level) in oocytes injected with mRNA from Embryonic Day 15 brain and increased postnatally to adult levels. The expression of voltage-dependent sodium and calcium channels was small in oocytes injected with mRNA from embryonic animals and increased postnatally to reach a maximum in oocytes injected with mRNA from adult animals.

Aging↗
PubMed1985

Multisequence comparisons in protein coding genes. Search for functional constraints.

A very powerful method for detecting functional constraints operative in biological macromolecules is presented. This method entails performing a base permanence analysis of protein coding genes at each codon position simultaneously in different species. It calculates the degree of permanence of subregions of the gene by dividing it into segments, c codons long, counting how many sites remain unchanged in each segment among all species compared. By comparing the base permanence among several sequences with the expectations based on a stochastic evolutionary process, gene regions showing different degrees of conservation can be selected. This means that wherever the permanence deviates significantly from the expected value generated by the simulation, the corresponding regions are considered "constrained" or "hypervariable". The constrained regions are of two types: alpha and beta. The alpha regions result from constraints at the amino acid level, whereas the beta regions are those probably involved in "control" processing. The method has been applied to mitochondrial genes coding for subunit 6 of the ATPase and subunit 1 of the cytochrome oxidase in four mammalian species: human, rat, mouse, and cow. In the two mitochondrial genes a few regions that are highly conserved in all codon positions have been identified. Among these regions a sequence, common to both genes, that is complementary to a strongly conserved region of 12S rRNA has been found. This method can also be of great help in studying molecular evolution mechanisms.

Amino Acid Sequence↗