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At least 217 records · Page 12Linked to original sources
PubMed2003

Gene conversion as a source of nucleotide diversity in Plasmodium falciparum.

Examination of polymorphisms in the Plasmodium falciparum gene for falcipain 2 revealed that this gene is one of two paralogs separated by 10.8 kb in chromosome 11. We designate the annotated gene denoted chr11.gen_424 as encoding falcipain 2A and the annotated gene denoted chr11.gen_427 as encoding falcipain 2B. The paralogs are 96% identical at the nucleotide level and 93% identical at the amino acid level. The consensus sequences differ in 31/309 synonymous sites and 45/1140 nonsynonymous sites, including three amino acid replacements (V393I, A400P, and Q414E) that are near the catalytic site and that may affect substrate affinity or specificity. In six reference isolates, among 36 synonymous sites and 46 nonsynonymous sites that are polymorphic in the gene for falcipain 2A, falcipain 2B, or both, significant spatial clustering is observed. All but one of the polymorphisms appear to result from gene conversion between the paralogs. The estimated rate of gene conversion between the paralogs may be as many as 1,400 to 1,700 times greater than the rate of mutation. Owing to gene conversion, one of the falcipain 2A alleles is more similar to the falcipain 2B alleles than it is to other falcipain 2A alleles. Divergence among the synonymous sites suggests that the paralogous genes last shared a common ancestor 15.2 MYA, with a range of 8.8 to 20.6 MYA. During this period, the paralogs have acquired 0.10 synonymous substitutions per synonymous site in the coding region. The 5' and 3' flanking regions differ in 47.7% and 39.8% of the nucleotide sites, respectively. Hence synonymous sites and flanking regions are not conserved in sequence in spite of their high AT content and T skew.

Animals↗
PubMed2005

Sequence transfers between variable regions in a mouse antibody transgene can occur by gene conversion.

Different vertebrate species show widely differing usage of somatic hyperconversion (SHC) as a mechanism for diversifying expressed Ab V genes. The basis for the differing levels of SHC in different species is not known. Although no clear evidence for SHC has been found in normal mouse B cells, transgenic mice carrying high-copy numbers of a gene construct designed to optimize detection of SHC have previously been shown to exhibit sequence transfers that resemble gene conversion events. However, these transgene sequence transfers could reflect multistep or reciprocal DNA recombination events rather than gene conversions. We now find in low-copy number transgenic mice that transgene sequence transfers can exhibit the unidirectional sequence information movement that is a hallmark of gene conversion. This indicates that gene conversion between V region sequences can occur in mouse B cells; we propose that the lack of efficient SHC contributions to Ab diversification in normal mice may be due, at least in part, to the particular pattern of V gene recombinational accessibility that occurs in differentiating mouse B cells.

Amino Acid Sequence↗
PubMed1985

Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution.

The fetal globin genes G gamma and A gamma from one chromosome of a chimpanzee (Pan troglodytes) were sequenced and found to be closely similar to the corresponding genes of man and the gorilla. These genes contain identical promoter and termination signals and have exons 1 and 2 separated by the conserved short intron 1 (122 bp) and exons 2 and 3 separated by the more rapidly evolving, larger intron 2 (893 bp and 887 bp in chimpanzee G gamma and A gamma, respectively). Each intron 2 has a stretch of simple sequence DNA (TG)n serving possibly as a "hot spot" for recombination. The two chimpanzee genes encode polypeptide chains that differ only at position 136 (glycine in G gamma and alanine in A gamma) and that are identical to the corresponding human chains, which have aspartic acid at position 73 and lysine at 104 in contrast to glycine and arginine at these respective positions of the gorilla A gamma chain. Phylogenetic analysis by the parsimony method revealed four silent (synonymous) base substitutions in evolutionary descent of the chimpanzee G gamma and A gamma codons and none in the human and gorilla codons. These Homininae (Pan, Homo, Gorilla) coding sequences evolved at one-tenth the average mammalian rate for nonsynonymous and one-fourth that for synonymous substitutions. Three sequence regions that were affected by gene conversions between chimpanzee G gamma and A gamma loci were identified: one extended 3' of the hot spot with G gamma replaced by the A gamma sequence, another extended 5' of the hot spot with A gamma replaced by G gamma, and the third conversion extended from the 5' flanking to the 5' end of intron 2, with G gamma replaced here by the A gamma sequence. A conversion similar to this third one has occurred independently in the descent of the gorilla genes. The four previously identified conversions, labeled C1-C4 (Scott et al. 1984), were substantiated with the addition of the chimpanzee genes to our analysis (C1 being shared by all three hominines and C2, C3, and C4 being found only in humans). Thus, the fetal genes from all three of these hominine species have been active in gene conversions during the descent of each species.

Animals↗
PubMed1992

Effect of donor copy number on the rate of gene conversion in the yeast Saccharomyces cerevisiae.

Nonreciprocal recombination (gene conversion) between homologous sequences at nonhomologous locations in the genome occurs readily in the yeast Saccharomyces cerevisiae. In order to test whether the rate of gene conversion is dependent on the number of homologous copies available in the cell to act as donors of information, the level of conversion of a defined allele was measured in strains carrying plasmids containing homologous sequences. The level of recombination was elevated in a strain carrying multiple copies of the plasmid, compared with the same strain carrying a single copy of the homologous sequences either on a plasmid or integrated in the genome. Thus, the level of conversion is proportional to the number of copies of donor sequences present in the cell. We discuss these results within the framework of currently favoured models of recombination.

Blotting, Southern↗
PubMed1992

A meiotic gene conversion gradient opposite to the direction of transcription.

Genetic recombination involves classical crossing-over and gene conversion (aberrant segregation). In fungi that produce an ascus containing four spores, a gene conversion event is manifested as 3:1 or 1:3 (or more rarely 4:0 or 0:4) segregations, in contrast to the normal mendelian 2:2 segregation. Polarity is one of the properties of gene conversion; in almost all cases the frequency of conversion exhibits a gradient across the gene monitored. The frequency of conversion is usually independent of the specific allele used as a marker, but dependent on its location. An interpretation of conversion polarity is that it is caused by the existence of specific initiation sites for meiotic recombination, located at the high end of the polarity gradient. Here we show that the polarity gradient for the HIS2 gene of Saccharomyces cerevisiae is high at the 3' end of the gene, implying that the promoter of HIS2 is not the initiation site.

Alleles↗
PubMed1997

Role of gene conversion in generating polymorphisms at major histocompatibility complex loci.

Multigene families are known to be evolving under continued occurrence of unequal crossing-over and gene conversion, and MHC loci are no exceptions. Population genetic models of diversifying selection, with intra- and inter-locus gene conversion were studied by computer simulations. Weak selection at individual amino acid site is shown to be quite effective in enhancing polymorphisms, if gene conversion occurs. This is caused by the appearance of coadapted segments of mutations in which recombination tends to be suppressed. In addition to the global type of diversifying selection, endemic type of selection was introduced in some sets of simulations to find out a mechanism of the rapid allelic turnover of South American Indians. Strong selection is assumed such that the most common two alleles become lethal in one generation. If this endemic selection occurs periodically, allelic turnover by intralocus gene conversion is shown to become rapid. Hence, interaction of selection and gene conversion has a profound effect on MHC polymorphisms.

Alleles↗
PubMed1995

Evidence for gene conversion in the amylase multigene family of Drosophila pseudoobscura.

The alpha-amylase (Amy) multigene family in Drosophila pseudoobscura is located on the third chromosome, which is polymorphic for more than 40 inverted gene arrangements. The number of copies in this family ranges from one to three, depending on the arrangement in question. A previous study of the three Amy genes from the Standard (ST) arrangement suggested either that duplicated copies (Amy2 and Amy3) are functionally constrained or that they are undergoing gene conversion with Amy1. In order to elucidate further the pattern of molecular evolution in this family, we cloned and sequenced four additional Amy genes, two from the Santa Cruz (SC) and two from the Chiricahua (CH) gene arrangement. Of the two alternatives, only the hypothesis of gene conversion is supported by the sequence analysis. The homogenization effect of gene conversion has been strongest in SC, whose copies differ by only two nucleotides, less noticeable in ST, and negligible in the CH. Furthermore, the action of gene conversion is apparently localized, occurring only in the coding region. Interestingly, these results concur with the findings of other workers for the duplicated Amy genes in the Drosophila melanogaster group. Thus, the occurrence of gene conversion in the Amy multigene family seems to be a common feature in the Drosophila species studied so far.

Animals↗
PubMed1998

Evolution of somatic hypermutation and gene conversion in adaptive immunity.

Examples of somatic hypermutation of antigen receptor genes can be seen in most lineages of vertebrates, including the cartilaginous fish. Analysis of the phylogenetic data reveals that two distinctive features of the mechanism are shared by most species studied: the mutation hot spot sequence AGY, and a preponderance of point mutations. These data suggest that some of the components of the machinery are shared between ectotherms and mammals. However, unique characters in particular species may have occurred by independent recruitment of novel factors onto the mechanism. A spotty phylogenetic distribution of gene conversion has also been revealed and can be explained if the two mechanisms share some characteristics. Both mutation and conversion require transcription-related sequences and/or factors. We theorized that targeting to V genes can be attained by a paused replication fork that has collided with a transcription complex stalled by a defective Ig transcription activator; the paused replication fork results in recruitment of an error-prone translesion synthesis DNA polymerase (somatic hypermutation) or of DNA repair mechanisms with homologous recombination (gene conversion). In addition, the pathway recruited in different species may be directed by the degree of homology among V genes.

Animals↗
PubMed1986

The repertoire of silent pilus genes in Neisseria gonorrhoeae: evidence for gene conversion.

To investigate the significance of silent gene loci for pilus antigenic variation in N. gonorrhoeae, we determined the nucleotide sequence of the major silent locus, pilS1. The pilS1 locus contains six tandem pilus gene copies linked by a 39 bp repeat sequence also present in the expression loci. All silent copies lack the common N-terminal coding sequence of pilin, containing instead variant sequence information that constitutes a semivariable (SV) and a hypervariable (HV) domain. The SV and HV domains are interspersed with short, strictly conserved (C) regions flanking small cassettes of variable sequence information. It appears that such minicassettes from silent copies can be duplicated and transferred to other silent or expression genes by means of gene conversion.

Amino Acid Sequence↗
PubMed2006

A revised evolutionary history of the CYP1A subfamily: gene duplication, gene conversion, and positive selection.

Members of cytochrome P450 subfamily 1A (CYP1As) are involved in detoxification and bioactivation of common environmental pollutants. Understanding the functional evolution of these genes is essential to predicting and interpreting species differences in sensitivity to toxicity caused by such chemicals. The CYP1A gene subfamily comprises a single ancestral representative in most fish species and two paralogs in higher vertebrates, including birds and mammals. Phylogenetic analysis of complete coding sequences suggests that mammalian and bird paralog pairs (CYP1A1/2 and CYP1A4/5, respectively) are the result of independent gene duplication events. However, comparison of vertebrate genome sequences revealed that CYP1A genes lie within an extended region of conserved fine-scale synteny, suggesting that avian and mammalian CYP1A paralogs share a common genomic history. Algorithms designed to detect recombination between nucleotide sequences indicate that gene conversion has homogenized most of the length of the chicken CYP1A genes, as well as the 5' end of mammalian CYP1As. Together, these data indicate that avian and mammalian CYP1A paralog pairs resulted from a single gene duplication event and that extensive gene conversion is responsible for the exceptionally high degree of sequence similarity between CYP1A4 and CYP1A5. Elevated nonsynonymous/synonymous substitution ratios within a putatively unconverted stretch of approximately 250 bp suggests that positive selection may have reduced the effective rate of gene conversion in this region, which contains two substrate recognition sites. This work significantly alters our understanding of functional evolution in the CYP1A subfamily, suggesting that gene conversion and positive selection have been the dominant processes of sequence evolution.

Animals↗
PubMed1999

Differences in gene conversion rates among exons between HLA-A and HLA-B loci.

To examine whether gene conversion occurs between two homologous loci of HLA-A and HLA-B, DNA sequences were compared and the differences or the numbers of substitutions per site at synonymous and nonsynonymous sites were calculated in the coding region and in the non-coding region. (1) Totally differences at synonymous sites in introns and coding regions are small as compared with the differences in the 5' flanking region. This indicates that gene conversion should occur between HLA-A and HLA-B loci. (2) In exon2 and exon3, the differences at synonymous sites are smaller than at nonsynonymous sites. This suggests that these exons are subject to positive natural selection, which is consistent with the reports of Hughes and Nei [1,2], because exon2 and exon3 encode alpha 1 and alpha 2 domains of the HLA molecule respectively which include mainly the antigen recognition sites (ARS). (3) in exon4, the difference at the synonymous site is the same as that in the 5' flanking region, which suggests that gene conversion does not frequently occur. The difference in this exon is extremely small at the nonsynonymous sites. This exon encodes the alpha 3 domain which does not have the antigen recognition sites but have an important function in maintaining the structure of the HLA molecule. From the above results, it can be concluded that gene conversion between HLA-A and HLA-B occurs more frequently in the two exons, exon2 and exon3 which have ARS regions. Furthermore, to examine a possibility that the variability of GC content along sequence influences the difference, the GC content was calculated along the sequence.

Alleles↗
PubMed1994

Meiotic gene conversion tract length distribution within the rosy locus of Drosophila melanogaster.

Employing extensive co-conversion data for selected and unselected sites of known molecular location in the rosy locus of Drosophila. we determine the parameters of meiotic gene conversion tract length distribution. The tract length distribution for gene conversion events can be approximated by the equation P(L > or = n) = phi n where P is the probability that tract length (L) is greater than or equal to a specified number of nucleotides (n). From the co-conversion data, a maximum likelihood estimate with standard error for phi is 0.99717 +/- 0.00026, corresponding to a mean conversion tract length of 352 base pairs. (Thus, gene conversion tract lengths are sufficiently small to allow for extensive shuffling of DNA sequence polymorphisms within a gene). For selected site conversions there is a bias towards recovery of longer tracts. The distribution of conversion tract lengths associated with selected sites can be approximated by the equation P(L > or = n/ selected) = phi n(1 - n + n/phi), where P is now the probability that a selected site tract length (L) is greater than or equal to a specified number of nucleotides (n). For the optimal value of phi determined from the co-conversion analysis, the mean conversion tract length for selected sites is 706 base pairs. We discuss, in the light of this and other studies, the relationship between meiotic gene conversion and P element excision induced gap repair and determine that they are distinct processes defined by different parameters and, possibly, mechanisms.

Animals↗
PubMed1991

Phylogenetic scanning: a computer-assisted algorithm for mapping gene conversions and other recombinational events.

An algorithm, 'phylogenetic scanning', is described for mapping gene conversion events where comparative DNA sequence data are available from different species. In this algorithm, sets of hypothetical phylogenetic trees are constructed that describe possible sequence relationships due to gene conversions in different species lineages; these trees are then evaluated by the principle of parsimony at intervals in the sequence alignment. When used to map gene conversion events that occurred between the pair of gamma-globin genes of higher primates, the algorithm gives results nearly identical to those obtained using a tedious manual approach. Suggestions are also provided for adaptation of this procedure to the analysis of other recombination events.

Algorithms↗
PubMed1990

Decreasing gradients of gene conversion on both sides of the initiation site for meiotic recombination at the ARG4 locus in yeast.

We have constructed eight restriction site polymorphisms in the DED81-ARG4 region and examined their behavior during meiotic recombination. Tetrad analysis reveals decreasing gradients of gene conversion on both sides of the initiation site for meiotic recombination at the ARG4 locus, extending on one side into the ARG4 gene, and on the other side into the adjacent DED81 gene. Gene conversion events can extend in both directions from the initiation site as the result of a single meiotic event. There is a second gradient of gene conversion in DED81, with high levels near the 5' end of the gene and low levels near the middle of the gene. The peaks of gene conversion activity for the DED81 and ARG4 gradients map to regions where double-strand breaks are found during meiosis. The implications of these results for models of meiotic gene conversion are discussed.

Chromosome Mapping↗
PubMed2002

Gene duplication and gene conversion shape the evolution of archaeal chaperonins.

Chaperonins are multi-subunit double-ring complexes that mediate the folding of nascent or denatured proteins. Gene duplication has been a potent force in the evolution of chaperonins in Archaea. Here we show that gene conversion has also been an important factor. We utilized a novel maximum likehood-based phylogenetic method for scanning DNA sequence alignments for regions of anomalous phylogenetic signal, such as those affected by gene conversion. Our results suggest that in crenarchaeotes, where an ancient gene duplication producing alpha and beta subunits took place in the common ancestor of the Pyrodictium, Aeropyrum, Pyrobaculum and Sulfolobus lineages, multiple independent gene conversions have occurred between the alpha and beta genes independently in each of these groups. Significantly, the conversions have repeatedly homogenized the region of the gene encoding the substrate-binding domain. This suggests that while the alpha and beta subunits in crenarchaeotes share only 50-60% overall amino acid sequence identity, they do not possess distinct roles in the binding of substrate. Cryptic gene conversion between distantly related paralogs may be more common than is currently appreciated, and could be a significant factor in slowing the functional differentiation of proteins encoded by duplicate genes long after their duplication.

Amino Acid Sequence↗
PubMed1994

Loss of phylogenetic information in chorion gene families of Bombyx mori gene conversion.

The silkmoth chorion has provided a stimulating model for the study of evolution and developmental regulation of gene families. Previous attempts at inferring relationships among chorion sequences have been based on pairwise comparisons of overall similarity, a potentially problematic approach. To remedy this, we identified the alignable regions of low sequence variability and then analyzed this restricted database by parsimony and neighbor-joining methods. At the deepest level, the chorion sequence tree is split into two branches, called "alpha" and "beta." Within each branch, early- and late-expressing genes each constitute monophyletic groups, while the situation with middle-expressing genes remains uncertain. The HcB gene family appears to be the most basal beta-branch group, but this conclusion is qualified because the effect of gene conversion on branching order is unknown. Previous studies by Eickbush and colleagues have strongly suggested that ErA, HcA, and HcB families undergo gene conversion within a gene family, whereas the ErB family does not. The occurrence of conversion correlates with a particular tree structure; namely, branch lengths are much greater at the base of the family than at higher internodes and terminal branches. These observations raise the possibility that chorion gene families are defined by gene conversion events (reticulate evolution) rather than by descent with modification (synapomorphy).

Animals↗
PubMed1994

Fine-resolution mapping of spontaneous and double-strand break-induced gene conversion tracts in Saccharomyces cerevisiae reveals reversible mitotic conversion polarity.

Spontaneous and double-strand break (DSB)-induced gene conversion was examined in alleles of the Saccharomyces cerevisiae ura3 gene containing nine phenotypically silent markers and an HO nuclease recognition site. Conversions of these alleles, carried on ARS1/CEN4 plasmids, involved interactions with heteroalleles on chromosome V and were stimulated by DSBs created at HO sites. Crossovers that integrate plasmids into chromosomes were not detected since the resultant dicentric chromosomes would be lethal. Converted alleles in shuttle plasmids were easily transferred to Escherichia coli and analyzed for marker conversion, facilitating the characterization of more than 400 independent products from five crosses. This analysis revealed several new features of gene conversions. The average length of DSB-induced conversion tracts was 200 to 300 bp, although about 20% were very short (less than 53 bp). About 20% of spontaneous tracts also were also less than 53 bp, but spontaneous tracts were on average about 40% longer than DSB-induced tracts. Most tracts were continuous, but 3% had discontinuous conversion patterns, indicating that extensive heteroduplex DNA is formed during at least this fraction of events. Mismatches in heteroduplex DNA were repaired in both directions, and repair tracts as short as 44 bp were observed. Surprisingly, most DSB-induced gene conversion tracts were unidirectional and exhibited a reversible polarity that depended on the locations of DSBs and frameshift mutations in recipient and donor alleles.

Alleles↗