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J Jurka

Publications and source records attributed to J Jurka.

At least 37 records · Page 2Linked to original sources
PubMed1997

Sequence patterns indicate an enzymatic involvement in integration of mammalian retroposons.

It is commonly accepted that the reverse-transcribed cellular RNA molecules, called retroposons, integrate at staggered breaks in mammalian chromosomes. However, unlike what was previously thought, most of the staggered breaks are not generated by random nicking. One of the two nicks involved is primarily associated with the 5'-TTAAAA hexanucleotide and its variants derived by a single base substitution, particularly A --> G and T --> C. It is probably generated in the antisense strand between the consensus bases 3'-AA and TTTT complementary to 5'-TTAAAA. The sense strand is nicked at variable distances from the TTAAAA consensus site toward the 3' end, preferably within 15-16 base pairs. The base composition near the second nicking site is also nonrandom at positions preceding the nick. On the basis of the observed sequence patterns it is proposed that integration of mammalian retroposons is mediated by an enzyme with endonucleolytic activity. The best candidate for such enzyme may be the reverse transcriptase encoded by the L1 non-long-terminal-repeat retrotransposon, which contains a freshly reported domain homologous to the apurinic/apyrimidinic (AP) endonuclease family [Martin, F., Olivares, M., Lopez, M. C. & Alonso, C. (1996) Trends Biochem. Sci. 21, 283-285; Feng, Q., Moran, J. V., Kazazian, H. H. & Boeke, J. D. (1996) Cell 87, 905-916] and shows nicking in vitro with preference for targets similar to 5'-TTAAAA/3'-AATTTT consensus sequence [Feng, Q., Moran, J. V., Kazazian, H. H. & Boeke, J. D. (1996) Cell 87, 905-916]. A model for integration of mammalian retroposons based on the presented data is discussed.

Animals↗
PubMed1997

The length distribution of perfect dimer repetitive DNA is consistent with its evolution by an unbiased single-step mutation process.

We have examined the length distribution of perfect dimer repeats, where perfect means uninterrupted by any other base, using data from GenBank on primates and rodents. Virtually no lengths greater than 30 repeats are found, except for rodent AG repeats, which extend to 35. Comparable numbers of long AC and AG repeats suggest that they have not been selected for special functions or DNA structures. We have compared the data with predictions of two models: (1) a Bernoulli Model in which bases are assumed equally likely and distributed at random and (2) an Unbiased Random Walk Model (URWM) in which repeats are permitted to change length by plus or minus one unit, with equal probabilities, and in which base substitutions are allowed to destroy long perfect repeats, producing two shorter perfect repeats. The source of repeats is assumed to be from single base substutions from neighboring sequences, i.e., those differing from the perfect repeat by a single base. Mutation rates either independent of repeat length or proportional to length were considered. An upper limit to the lengths L approximately 30 is assumed and isolated dimers are assumed unable to expand, so that there are absorbing barriers to the random walk at lengths 1 and L + 1, and a steady state of lengths is reached. With these assumptions and estimated values for the rates of length mutation and base substitution, reasonable agreement is found with the data for lengths > 5 repeats. Shorter repeats, of lengths </= 3 are in general agreement with the Bernoulli Model. By reducing the rate of length mutations for n </= 5, it is possible to obtain reasonable agreement with the full range of data. For these reduced rates, the times between length mutations become comparable to those suggested for a bottleneck in the evolution of Homo sapiens, which may be the reason for low heterozygosity of short repeats.

Animals↗
PubMed1996

The age of Alu subfamilies.

Using Kimura's distance measure we have calculated the average age of all major Alu subfamilies based on the most recent available data. We conclude that AluJ sequences are some 26 Myr older than previously thought. Furthermore, the origin of the FLA (Free Left Arm) Alu family can be traced back to the very beginning of the mammalian radiation. One new minor subfamily is reported and discussed in the context of sequence diversity in major Alu subfamilies.

Animals↗
PubMed1996

Integration of retroposable elements in mammals: selection of target sites.

Genomic DNA fragments generated by the reverse transcription of cellular RNA are called retroposons. Because they are flanked by short repeats, mammalian retroposons are believed to integrate at staggered chromosomal breaks. Recently, a significant sequence pattern associated with the integration of Alu and ID repeats was identified (Jurka 1996). It is represented by the 5' TTAAAA consensus sequence around the 5' ends of flanking repeats of Alu, ID, as well as, of B1 and B2 retroposed elements as shown in this paper. This consensus is a potential target for enzymatic nicking which probably occurs in the complementary strand between 3' AA and the following 3' TTTT bases. The first four bases of the flanking repeats corresponding to the 3' TTTT consensus sequence show some sequence variations that may be affected by complementary base pairing between the A-rich RNA tails and the DNA target sequences prior to nicking and reverse transcription. We discuss potential evidence for such base pairing based on correlated variations in nucleotide composition of different tail and target regions.

Animals↗
PubMed1996

CENSOR--a program for identification and elimination of repetitive elements from DNA sequences.

CENSOR is a program designed to identify and eliminate fragments of DNA sequences homologous to any chosen reference sequences, in particular to repetitive elements. CENSOR is based on two principal algorithms of Smith & Waterman (1981) [J. Mol. Biol. 147, 195] and Wilbur & Lipman (1983) [Proc. Natl. Acad. Sci. U.S.A. 80, 726]. It includes several pre-set sensitivity levels based on both biological and statistical criteria which help to distinguish between aligned pairs of homologous and non-homologous sequences. CENSOR has been implemented in C/C + + in the SUN/UNIX environment.

Algorithms↗
PubMed1995

Comparison of repetitive elements in the third intron of human and rodent mitochondrial benzodiazepine receptor-encoding genes.

The third intron of the mitochondrial benzodiazepine receptor (MBR)-encoding gene was sequenced from hamster, mouse and human. The rodent species were found to include an Alu-like sequence, as was first discovered in the rat gene. Differences with the rat intron were evident by an insertion of an additional B1 element in the hamster and the introduction of a complete and two partial B2 sequences in the mouse intron. The human intron contained a cluster of four Alu sequences; however, all of these repetitive elements were found to be in the opposite orientation relative to the Alu-like sequence present in the rodent genes. These findings support the possibility that the rodent Alu-like sequence is a remnant of a retropositional insertion in this gene prior to the divergence of rodent species. Because the human intron does not contain the same Alu remnant, it cannot be concluded that the rodent sequence represents an insertion of a primordial Alu element prior to the divergence of rodent and primate lineages.

Animals↗
PubMed1995

Ancestral, mammalian-wide subfamilies of LINE-1 repetitive sequences.

Analysis of the 3'-ends of approximately 900 separate human LINE-1 (L1) elements from primates revealed 47 contiguous but distinct subfamilies with the L1 family. Eight previously described medium reiteration frequency sequences (MERs) were found to be parts of ancient L1 untranslated 3'-regions which show little or no sequence similarity to the presently active L1 3'-end. Some of the major changes in 3'-end sequence can be explained by recombination events between different L1 repeats as well as between L1 and unrelated repetitive sequences. One of these sequences, MER42, is reported in this paper. With the set of consensus sequences for different subfamilies and their diagnostic features, it is possible to estimate the age of individual LINE-1 elements. Contrary to earlier suggestions, the majority of L1 copies in the human genome is very old; more than half of the identifiable elements were inserted into the genome before the mammalian radiation, as evidenced by elements at orthologous sites in human and other mammalian genomes. Multiple distinct L1 source genes seem to have been active simultaneously over long periods of time.

Amino Acid Sequence↗
PubMed1995

Ubiquitous mammalian-wide interspersed repeats (MIRs) are molecular fossils from the mesozoic era.

Short interspersed elements (SINEs) are ubiquitous in mammalian genomes. Remarkable variety of these repeats among placental orders indicates that most of them amplified in each lineage independently, following mammalian radiation. Here, we present an ancient family of repeats, whose sequence divergence and common occurrence among placental mammals, marsupials and monotremes indicate their amplification during the Mesozoic era. They are called MIRs for abundant Mammalian-wide Interspersed Repeats. With approximately 120,000 copies still detectable in the human genome (0.2-0.3% DNA), MIRs represent a 'fossilized' record of a major genetic event preceding the radiation of placental orders.

Animals↗
PubMed1995

Simple repetitive DNA sequences from primates: compilation and analysis.

Simple repeats composed of tandemly repeated units 1-6 nucleotides (nt) long have been extracted from a selected set of primate genomic DNA sequences. Of the 501 theoretically possible, different types of repeats only 67 were present in the analyzed database in at least two different size ranges over 12 nt. They include all simple repeats known to be polymorphic in the primate genome. A list of moderately expanding and nonexpanding oligonucleotide patterns has also been included. Furthermore, we have compiled statistical data with emphasis on the overall variability of the most abundant 67 types of repeats. We have demonstrated that the expandability of at least some simple repeats may be affected by the overall base composition and by flanking sequences. In particular, the occurrence of tandemly repeated CAG and GCC triplets in exons positively correlates with their G+C content. We also noted that in the vicinity of Alu sequences tetrameric repeats are more abundant than in the total genomic DNA. This paper can be used as a comprehensive guide in identification of the most abundant and potentially polymorphic simple repeats. It is also of broader significance as a step toward understanding the contribution of flanking sequences and the overall sequence composition to variability of simple repeats.

Animals↗
PubMed1994

A young Alu subfamily amplified independently in human and African great apes lineages.

A variety of Alu subfamilies amplified in primate genomes at different evolutionary time periods. Alu Sb2 belongs to a group of young subfamilies with a characteristic two-nucleotide deletion at positions 65/66. It consists of repeats having a 7-nucleotide duplication of a sequence segment involving positions 246 through 252. The presence of Sb2 inserts was examined in five genomic loci in 120 human DNA samples as well as in DNAs of higher primates. The lack of the insertional polymorphism seen at four human loci and the absence of orthologous inserts in apes indicated that the examined repeats retroposed early in the human lineage, but following the divergence of great apes. On the other hand, similar analysis of the fifth locus (butyrylcholinesterase gene) suggested contemporary retropositional activity of this subfamily. By a semi-quantitative PCR, using a primer pair specific for Sb2 repeats, we estimated their copy number at about 1500 per human haploid genome; the corresponding numbers in chimpanzee and gorilla were two orders of magnitude lower, while in orangutan and gibbon the presence of Sb2 Alu was hardly detectable. Sequence analysis of PCR-amplified Sb2 repeats from human and African great apes is consistent with the model in which the founding of Sb2 subfamily variants occurred independently in chimpanzee, gorilla and human lineages.

Animals↗
PubMed1994

Induction of heat-stable enterotoxin receptor activity by a human Alu repeat.

The heat-stable enterotoxins (ST) elaborated by enterotoxigenic Escherichia coli are a family of small cysteine-rich peptides that bind to specific epithelial receptors in the mammalian intestine, causing a secretory diarrhea. The expression of ST receptors is tightly regulated; they are found primarily in intestine, and their expression is developmentally modulated. One receptor for ST has been cloned, and its cDNA encodes a approximately 120-kDa particulate guanylyl cyclase (guanylyl cyclase-C). Recent studies suggest that there are additional ST receptors that are not homologous to guanylyl cyclase-C. We used an expression cloning strategy to identify intestinal mRNAs that lead to expression of ST receptor activity in transfected cells. Using an ST-specific affinity panning system, we identified a novel 1891-base pair cDNA that does not encode a receptor protein, but instead, consists primarily of untranslated sequence. This cDNA induced receptor activity in both COS and 293 embryonic kidney cells. Northern analysis of the T84 human intestinal cell line, from which this cDNA was cloned, suggests that it is part of a 7.8-kilobase mRNA transcript. This transcript was also identified in human small intestine and colon, as well as in several extra-intestinal tissues. Functional analysis of subcloned fragments reveals that ST binding activity is induced by a 457-base pair human Alu repetitive sequence within the cDNA and that the phenotype is independent of orientation. These findings suggest that a human Alu element induces expression of a unique ST receptor by a transacting mechanism. An unrelated Alu-rich genomic clone did not confer ST binding, suggesting that there may be structural and functional specificity within individual Alu sequences.

Animals↗
PubMed1994

Repetitive DNA in and around translocation breakpoints of the Philadelphia chromosome.

This paper describes systematic sequence studies of repetitive DNA in and around translocation breakpoints on chromosomes 9 and 22, which are involved in the formation of the Philadelphia chromosome in acute leukemias. In addition to Alu repeats described in previous studies, the breakpoint regions appear to contain many other repetitive elements, including a member of a new repetitive family (MER34) reported in this paper. Identification of these repeats broadens current studies on the possible involvement of repetitive DNA in this intensely studied chromosomal translocation.

Base Sequence↗
PubMed1993

Identification and characterization of new human medium reiteration frequency repeats.

We report nine new families of human medium reiteration frequency interspersed repetitive elements (MER elements). They were identified by computer-assisted analyses. Six of them were independently confirmed as repetitive families by DNA-DNA hybridization, and the number of elements for each of these families was estimated by plaque hybridization assay. The involvement of some of the reported MER elements in genetic rearrangements is demonstrated.

Base Sequence↗
PubMed1993

Dense Alu clustering and a potential new member of the NF kappa B family within a 90 kilobase HLA class III segment.

We have conducted a detailed structural analysis of 90 kilobases (kb) of the HLA Class III region from the Bat2 gene at the centromeric end to 23 kb beyond TNF. A single contig of 80 kb was sequenced entirely with a group of four smaller contigs covering 10 kb being only partly sequenced. This region contains four known genes and a novel telomeric potential coding region. The genes are bracketed by long, dense clusters of Alu repeats belonging to all the major families. At least six new families of MER repeats and one pseudogene are intercalated within and between the Alu clusters. The most telomeric 3.8 kb contains three potential exons, one of which bears strong homology to the ankyrin domain of the DNA binding factors NF kappa B and I kappa B.

Amino Acid Sequence↗
PubMed1993

Discovering simple DNA sequences by the algorithmic significance method.

A new method, 'algorithmic significance', is proposed as a tool for discovery of patterns in DNA sequences. The main idea is that patterns can be discovered by finding ways to encode the observed data concisely. In this sense, the method can be viewed as a formal version of the Occam's Razor principle. In this paper the method is applied to discover significantly simple DNA sequences. We define DNA sequences to be simple if they contain repeated occurrences of certain 'words' and thus can be encoded in a small number of bits. Such definition includes minisatellites and microsatellites. A standard dynamic programming algorithm for data compression is applied to compute the minimal encoding lengths of sequences in linear time. An electronic mail server for identification of simple sequences based on the proposed method has been installed at the Internet address pythia/anl.gov.

Algorithms↗
PubMed1992

Prototypic sequences for human repetitive DNA.

We report a collection of 53 prototypic sequences representing known families of repetitive elements from the human genome. The prototypic sequences are either consensus sequences or selected examples of repetitive sequences. The collection includes: prototypes for high and medium reiteration frequency interspersed repeats, long terminal repeats of endogenous retroviruses, alphoid repeats, telomere-associated repeats, and some miscellaneous repeats. The collection is annotated and available electronically.

Animals↗