The adsorption of organic molecules onto the surfaces of inorganic solids has long been considered a process relevant to the origin of life. We have determined the equilibrium adsorption isotherms for the nucleic acid purine and pyrimidine bases dissolved in water on the surface of crystalline graphite. The markedly different adsorption behavior of the bases describes an elutropic series: guanine > adenine > hypoxanthine > thymine > cytosine > uracil. We propose that such differential properties were relevant to the prebiotic chemistry of the bases and may have influenced the composition of the primordial genetic architecture.T he purine and pyrimidine coding elements of nucleic acids are products of putative prebiotic chemistries that invoke cyanide (1, 2) and have been synthesized in reactions that also yield amino acids (3). The prebiotic availability of these compounds supports the RNA World Hypothesis (4) for the origin of life, which presupposes that the first living system was a polymer(s) of catalytic RNA capable of self-replication that subsequently evolved the ability to encode more versatile peptide catalysts. RNA can act as both information carrier and catalyst (5) and, in the laboratory, can be coerced into different catalytic functions through directed Darwinian evolution (6).Despite these properties, there are severe difficulties with the de novo appearance of RNA, and, even in the most optimistic scenario, information-bearing molecule(s) capable of selfreplication must have first formed fortuitously from an astronomical range of possibilities (7). Although RNA-mediated catalysis and the nonenzymic polymerization of nucleotides (8,9) are well demonstrated, nucleic acid structure incorporates carbohydrate moieties. Formaldehyde, a seemingly ubiquitous compound, is regarded as the most plausible precursor of carbohydrates; however, cyanohydrin (glyconitrile) is the major highly stable product of reactions between formaldehyde and cyanide, withdrawing the latter from being a putative source of bases and amino acids (10). The recovery of nonbiogenic amino acids and bases from extraterrestrial debris (11) suggests the spatial-temporal separation of formaldehyde and cyanide. Life may have been initiated in the absence of carbohydrates, and it has been proposed that modern biology was preceded by a non-nucleic acid informational architecture (12, 13).Aperiodicity is required to convey information (14), and it has been demonstrated that aperiodic structures can self-assemble from aqueous mixtures of purine and pyrimidine bases adsorbed onto the surface of an uncharged inorganic crystalline mineral (15). The spontaneous formation of such structures suggests the existence of an organic, nonpolymeric informational architecture that may have had relevance to the origin of life.The adsorption of organic molecules onto inorganic solids has long been considered a relevant prebiotic process (16). The purine and pyrimidine bases adsorb spontaneously from aqueous media onto inorganic solids and have been observed o...

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Chronic myeloid leukaemia (CML) develops when two genes, BCR on chromosome 22 and ABL on chromosome 9, recombine to form a hybrid BCR-ABL gene with leukaemogenic properties. The mechanism which underlies this recombination is unknown, but additional chromosome sites may be involved to form complex BCR-ABL rearrangements. The majority of breakpoints in BCR occur within a 5 kb major breakpoint cluster region, M-Bcr. Here, we show that the 3' part of M-Bcr recombined within, or immediately adjacent to, Alu elements at the additional sites in all five complex BCR-ABL rearrangements that have been examined so far. This is a new finding which suggests that Alu sequences have an affinity for the BCR-ABL recombination process in complex rearrangements, and provides additional evidence for the association of these elements with somatic rearrangements which cause human leukaemia. We further show that sequence motifs similar to IgH switch pentamers and consensus binding sites of the lymphoid-associated Translin protein are present on one or more participating strands at 3'M-Bcr recombination sites. Motifs similar to Translin-binding sites were also identified within the Alu consensus. Expressed sequences mapped close to the breakpoint sites on other chromosomes in three of the five cases examined.

Previously proposed models of monolayers of adenine and guanine, based on scanning tunneling microscopy and atomic force microscopy images, have been critically examined. We have applied molecular mechanics computer simulations to these models and, where appropriate, examined additional scanning tunneling microscopy data. These findings support the proposed adenine structure based on low-energy diffraction analysis and molecular mechanics but indicate that the structure of the guanine monolayer on graphite is different from those previously proposed. These findings indicate that the energy-minimized adsorbate stuctures of both adenine and guanine form a similar molecular configuration on both graphite and molybdenum disulfide surfaces. It is speculated that the formation of these structures may have had some prebiotic relevance.

Differential DNA methylation of the parental alleles has been implicated in the establishment and maintenance of the monoallelic expression of imprinted genes. H19 and IGF2 are oppositely imprinted with only the maternal and the paternal alleles expressed, respectively. In Wilms tumor, a childhood renal neoplasm, loss of the H19/IGF2 imprinted expression pattern results in silencing of H19 and biallelic expression of IGF2. This was shown to be associated with biallelic methylation of the H19 promoter in the tumor and the adjacent kidney tissue suggesting that epigenetic H19 silencing is an early event in Wilms tumorigenesis. An imprinting mark region characterized by paternal allele-specific methylation has been suggested to reside in a GC-rich region of 400-base pair direct repeats starting at ؊2 kilobase pairs (kb) relative to the H19 transcription start and extending upstream. The upstream boundary of the potential paternal methylation imprint of the H19 gene has yet to be defined. We sought to define this upstream imprint boundary and investigate whether Wilms tumors with loss of imprinting are biallelically methylated in this imprinting mark region. The analysis of 6.6 kb of new upstream H19 sequence determined in this study identified a series of the direct 400-base pair repeats that extends to approximately ؊5.3 kb relative to the transcription start. DNA methylation analyses indicated that the upstream boundary of the potential imprint may coincide with the 5 end of the direct repeats. We found that Wilms tumors with loss of imprinting are biallelically methylated in the H19 upstream repeat region, and we suggest that pathological methylation in this region is the epigenetic error that initiates H19 silencing.Genomic imprinting describes the phenomenon of heritable parent-of-origin-specific expression of genes. The molecular mechanisms that determine the monoallelic expression of imprinted genes are to date not fully understood. However, it is a widely accepted concept that parental allele-specific DNA methylation plays an important role in the process.The insulin-like growth factor 2 (IGF2) and H19 genes are located in a cluster of imprinted genes on human chromosome 11p15.5 that is syntenic with the mouse distal chromosome 7. The maternally imprinted IGF2 gene is transcribed only from the paternal allele in most normal human tissues except for adult liver, choroid plexus, and leptomeninges (1, 2). In contrast, the H19 gene is paternally imprinted hence maternally transcribed (3-5). This reciprocal expression pattern is frequently lost in Wilms tumor, a childhood renal neoplasm, and in the overgrowth syndrome, Beckwith-Wiedemann syndrome, that predisposes to Wilms tumor either by maternal loss of heterozygosity at chromosome 11p15 or by loss of imprinting (LOI) 1 (6). LOI of IGF2 in Wilms tumor was first described by Rainier et al. (7)and Ogawa et al. (8). Since then several groups have shown that LOI of IGF2 in Wilms tumor and BeckwithWiedemann syndrome is associated with transcriptional repression and...

The experimental evidence for the spontaneous formation and structure determination of two-dimensional monolayers of the purine and pyrimidine bases is examined. The plausibility of such structures forming spontaneously at the solid-liquid interface following their prebiotic synthesis suggests a functional role for them in the emergence of life. It is proposed that prebiotic interactions of enantiomorphic monolayers of mixed base composition with racemic amino acids might be implicated in a simultaneous origin of a primitive genetic coding mechanism and biomolecular homochirality. The interactions of these monolayers with carbohydrates and other derivatives is also discussed.