Whole genome mining reveals a diverse repertoire of lanthionine synthetases and lanthipeptides among the genus Paenibacillus.

AIM: Lanthionine or methyllanthionine-containing lanthipeptides belongs to ribosomally synthesized and post-translationally modified peptides (RiPPs) family. Recent revolution in sequencing has made available huge genome sequence dataset of micro-organisms. In this study, we performed genome mining of the complete and partial genome sequences of 479 bacteria of the genus Paenibacillus to determine the diversity and distribution of lanthipeptide gene clusters. METHODS AND RESULTS: All genome sequences were annotated by RAST and subsequently analysed by BAGEL and antiSMASH. A total of 221 lanthipeptide gene clusters were identified in 127 strains of the genus Paenibacillus. One hundred and fifty gene clusters were found associated with the production of class I lanthipeptides while 58 and 13 gene clusters were related to class II and class IV lanthipeptide production respectively. Frequency of strains whose genomes encode putative lanthipeptide precursors was 26·5%. CONCLUSIONS: The results of lanthionine synthetases analysis suggested that diversity of lanthipeptides is much more than anticipated, while lanthionine synthetases must have been co-evolved among various species of the genus Paenibacillus. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report showing diversity and distribution of different classes of lanthipeptides among various species of the genus Paenibacillus. This study also reveals the novel lanthipeptide sequences which may be further developed as potential antimicrobials for therapeutic applications.

Hb Godavari [alpha 95(G2)Pro-->Thr]: a neutral amino acid substitution in the alpha 1 beta 2 interface that modifies the electrophoretic mobility of hemoglobin.

Hb Godavari [alpha 95(G2)Pro-->Thr] was characterized independently in two families of different ethnic origin. The first case, found in the Netherlands, involved an Indian patient. The second one was identified a few months later in an African family from Mali, living in France. Hb Godavari is the fourth example of a substitution involving neutral residues at position alpha 95(G2). In all these variants the electrophoretic pattern suggested that the structural modification unmasks a charged residue buried in the alpha 1 beta 2 contact area. The oxygen affinity of this abnormal hemoglobin was approximately 10% higher than that of Hb A; in the absence of 2,3-diphosphoglycerate, its cooperativity was moderately decreased, suggesting a slightly unstable T state.

Multiple recombination events are responsible for the heterogeneity of alpha(+)-thalassemia haplotypes among the forest tribes of Andhra Pradesh, India.

The presence of several polymorphic markers along the alpha-globin gene complex allows the identification of haplotypes associated with alpha-thalassemia determinants. These are found at very high frequencies in geographic areas where malaria is or has been endemic which suggests a positive selective role by the parasitic disease in favour of alpha(+)-thalassemia mutants. A population survey among forest tribal communities from Andhra Pradesh, India, revealed the prevalence and molecular heterogeneity of alpha(+)-thalassemia determinants presumably due to a long backdated malaria endemicity among these populations. Analysis of the tribal alpha-thalassemia haplotypes has shown a great degree of genetic heterogeneity which can be explained as the result of multiple recombination events in the presence of natural selection by malaria.

Field survey for sickle cell disease in the tribal population of East Godavari District, Andhra Pradesh.

Tribals have inhabited the hilly forest area in East Godavari District, Andhra Pradesh, South India in isolation for centuries. A field survey for sickle cell disease was conducted from 1978 to 1986 and electrophoresis on cellogel was carried out in 2,589 samples. The incidence of sickle gene varied in different castes among the tribals. A higher incidence was found in the Valmiki (31.5%), followed by the Konda Kammari (27%), Koya Dora (17.3%), Konda Reddy (13.4%), Koya (12.1%), Konda Kapu (6.8%), and others (4.2%). Harijans living in the tribal belt had an incidence of 16.1%.

Prevalence and molecular heterogeneity of alfa+ thalassemia in two tribal populations from Andhra Pradesh, India.

We describe here the screening of a small group of apparently healthy individuals belonging to the tribal communities of Koya Dora and Konda Reddi. A remarkably high incidence of deletion and nondeletion alpha + thalassemia mutants has been found with allele frequencies and distributions characteristic to each tribe. We have confirmed the strict relationship between Hb S levels and the number of alpha globin genes in double heterozygotes for the S gene and alpha thalassemia. In this population sample we did not find either heterozygous carriers of alpha 0 thalassemia (deletion of both alpha genes in "cis") or individuals showing hemolytic anemia due to inactivation of three alpha-globin genes (Hb H disease). Selection by malaria is most probably responsible for the prevalence of the various alpha + thalassemia haplotypes among the two tribal populations of Andhra Pradesh.

Alpha globin gene number: population and restriction endonuclease studies.

Restriction endonuclease analysis was used to test a proposed genetic model using alpha-globin gene number to account for the observed distributions of the proportions of hemoglobin (Hb) S in sickle cell trait. In a subsample of specimens collected during a population survey in India, these studies confirmed that the postulated genotype was present in 22 of the 23 individuals examined. In the study population, the number of alpha-globin genes explains about 90% of the variance in the proportion of HbS in sickle cell trait (r2 = 0.895, p less than 10(-10)).

Hemoglobin Hofu or alpha 2 beta 2 [126 (H4) Va1 leads to Glu] found in combination with hemoglobin S.

Hb Hofu, alpha 2 beta 2 [126 (H4) Va1 leads to Glu], was found in 10 members of 2 apparently unrelated Valmiki families in central India. None showed evidence of hemolysis and hemoglobin levels were normal in most. In two individuals, Hb Hofu occurred in combination with Hg S, but neither had clinical manifestations of sickle cell disease. In samples containing Hb Hofu, the isopropanol precipitation test was positive. Quantitation of the hemoglobin fractions by DEAE-cellulose chromatography showed that Hb Hofu constituted a mean of 23--25% of the total whether in combination with Hb A or Hb S.