Site specific induction of gene conversion: the effects of homozygosity of the ade6 mutant M26 of Schizosaccharomyces pombe on meiotic gene conversion.
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Adenine↗
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Molecular history of gene conversions in the primate fetal gamma-globin genes. Nucleotide sequences from the common gibbon, Hylobates lar.
Comparative and phylogenetic analyses of homologous sequences from closely related species reveal genetic events which have happened in the past and thus provide considerable insight into molecular genetic processes. One such process which has been especially important in the evolution of multigene families is gene conversion. The fetal gamma 1 and gamma 2-globin genes of catarrhine primates (humans, apes, and Old World monkeys) underwent numerous gene conversion events after they arose from a gene duplication event 25-35 million years ago. By including the gamma 1- and gamma 2-globin gene sequences from the common gibbon, Hylobates lar, the present work expands the gamma-globin data set to represent all major groups of hominoid primates. A computer-assisted algorithm is introduced which reveals converted DNA segments and provides results very similar to those obtained by site-by-site evolutionary reconstruction. Both methods provide strong evidence for at least 14 different converted stretches in catarrhine primates as well as five conversions in ancestral lineages. Features of gene conversions generalized from this molecular history are 1) conversions are restricted to regions maintaining high degrees of sequence similarity, 2) one gene may dominate in converting another gene, 3) sequences involved in conversions may accumulate changes more rapidly than expected, and 4) certain elements, such as polypurine/polypyrimidine [Y)n) and (TG)n elements, appear to be hotspots for initiating or terminating conversion events.
Amino Acid Sequence↗
Release of soluble pilin antigen coupled with gene conversion in Neisseria gonorrhoeae.
Gene conversion appears to be the frequent mechanism in Neisseria gonorrhoeae that leads to an altered expression of pilin, the subunit component of the pili. In this process segments of variable sequence information, the minicassettes, are transferred from silent storage loci into an expression locus. As a putative consequence of the rearrangement in the pilE gene, gonococci can enter a different phase of pilin production. Although the removal of a 7-amino acid leader peptide results in the production of typical P+ pilin used to form pili, the loss of an additional 39 amino acids yields S-pilin, a soluble form of pilin that is efficiently secreted into the extracellular environment. Both pilin types can coexist in an apparently homogeneous culture. Ps cells usually are piliated, although less extensively with regard to the length and the number of the pili when compared with P+ cells. Ps cells form T3/T4-type colonies also typical of nonpiliated cells (P-). The observations further suggest that the classical nonsecretory P- phenotype is not generated as a rule by precise gene conversion but rather by genetic changes that cause the production of an over-length pilin (L-pilin).
Amino Acid Sequence↗
Ablation of XRCC2/3 transforms immunoglobulin V gene conversion into somatic hypermutation.
After gene rearrangement, immunoglobulin V genes are further diversified by either somatic hypermutation or gene conversion. Hypermutation (in man and mouse) occurs by the fixation of individual, non-templated nucleotide substitutions. Gene conversion (in chicken) is templated by a set of upstream V pseudogenes. Here we show that if the RAD51 paralogues XRCC2, XRCC3 or RAD51B are ablated the pattern of diversification of the immunoglobulin V gene in the chicken DT40 B-cell lymphoma line exhibits a marked shift from one of gene conversion to one of somatic hypermutation. Non-templated, single-nucleotide substitutions are incorporated at high frequency specifically into the V domain, largely at G/C and with a marked hotspot preference. These mutant DT40 cell lines provide a tractable model for the genetic dissection of immunoglobulin hypermutation and the results support the idea that gene conversion and somatic hypermutation constitute distinct pathways for processing a common lesion in the immunoglobulin V gene. The marked induction of somatic hypermutation that is achieved by ablating the RAD51 paralogues is probably a consequence of modifying the recombination-mediated repair of such initiating lesions.
Animals↗
Evidence for segmental gene conversion between a cognate hsp 70 gene and the temperature-sensitively transcribed hsp70 genes of Trypanosoma brucei.
The protozoan parasite Trypanosoma brucei expresses several heat shock proteins of 70 kDa (hsp70). We show that, from 5' to 3', a diverged cognate hsp70 gene (gene 1) is separated by about 6 kb of DNA from a cluster of five identical hsp70 genes (genes 2-6). The hsp70 cognate gene has a predicted open reading frame of 676 amino-acids. The steady-state mRNA levels of gene 1 are unaffected by temperature shifts up to 42 degrees C. Hsps of diverse organisms share several fully conserved amino acid domains in the N-terminal region of the hsp70 proteins. These conserved amino acid domains are also observed in the T. brucei hsp70 genes 1-6. However they are, in contrast to the heat shock genes of other eukaryotes, encoded by nucleotide sequence blocks that are identical in all six hsp70 genes. These conserved domains, located in the 5' coding region, range in size from several to hundreds of nucleotides and are separated by highly diverged nucleotide sequences. The nucleotide sequence conservation between hsp70 gene 1 and hsp70 genes 2-6 indicates that selective sequence homogenization, presumably through gene conversion, maintained the amino acid sequence conservation.
Amino Acid Sequence↗
Recent duplication and inter-locus gene conversion in major histocompatibility class II genes in a teleost, the three-spined stickleback.
Using a bacterial artificial chromosome (BAC) library, we analysed a 99.5 kb genomic segment containing the major histocompatibility class II genes of a teleost, the three-spined stickleback Gasterosteus aculeatus. Experiments with G. aculeatus have provided direct evidence for balancing selection by pathogens and mate choice driving MH class II beta polymorphism. Two sets of paralogous class II alpha genes and beta genes in a tandem arrangement were identified, designated Gaac-DAA/DAB and Gaac-DBA/DBB. Expression analysis of the beta genes using single-strand conformation polymorphism revealed that both gene copies are expressed. Based on an analysis of pairwise nucleotide polymorphisms, we estimate that the duplication into two paralogous class II loci occurred only 1.2-2.4 million years ago, 1-2 orders of magnitude more recently than in other fish, bird or mammalian species. At the 3'-direction of the classical MH loci, we identified another seven genes or gene fragments, two of which (small inducible cytokine, complement regulatory factor) are related to immune function in other vertebrates. None of these genes were associated with MH class II genes in zebrafish, suggesting a markedly different organisation of the MH class II region in sticklebacks, and presumably, across bony fishes. When the nucleotide substitution pattern of the novel class II beta genes was analysed together with a representative sequence sample isolated from fish in northern Germany (n=27), we found that the peptide binding region of the Gaac-DAB and Gaac-DBB loci had undergone an inter-locus gene conversion (P=0.007). In accordance, we found a 10- to 20-fold higher frequency of CpG-islands on the MH class II segment compared to other species, a feature that may be conducive for inter-locus recombination.
Amino Acid Sequence↗
Gene conversion drives the evolution of HINTW, an ampliconic gene on the female-specific avian W chromosome.
The HINTW gene on the female-specific W chromosome of chicken and other birds is amplified and present in numerous copies. Moreover, as HINTW is distinctly different from its homolog on the Z chromosome (HINTZ), is a candidate gene in avian sex determination, and evolves rapidly under positive selection, it shows several common features to ampliconic and testis-specific genes on the mammalian Y chromosome. A phylogenetic analysis within galliform birds (chicken, turkey, quail, and pheasant) shows that individual HINTW copies within each species are more similar to each other than to gene copies of related species. Such convergent evolution is most easily explained by recurrent events of gene conversion, the rate of which we estimated at 10(-6)-10(-5) per site and generation. A significantly higher GC content of HINTW than of other W-linked genes is consistent with biased gene conversion increasing the fixation probability of mutations involving G and C nucleotides. Furthermore, and as a likely consequence, the neutral substitution rate is almost twice as high in HINTW as in other W-linked genes. The region on W encompassing the HINTW gene cluster is not covered in the initial assembly of the chicken genome, but analysis of raw sequence reads indicates that gene copy number is significantly higher than a previous estimate of 40. While sexual selection is one of several factors that potentially affect the evolution of ampliconic, male-specific genes on the mammalian Y chromosome, data from HINTW provide evidence that gene amplification followed by gene conversion can evolve in female-specific chromosomes in the absence of sexual selection. The presence of multiple and highly similar copies of HINTW may be related to protein function, but, more generally, amplification and conversion offers a means to the avoidance of accumulation of deleterious mutations in nonrecombining chromosomes.
Animals↗
Gene conversion tracts associated with crossovers in Rhizobium etli.
Gene conversion has been defined as the nonreciprocal transfer of information between homologous sequences. Despite its broad interest for genome evolution, the occurrence of this mechanism in bacteria has been difficult to ascertain due to the possible occurrence of multiple crossover events that would mimic gene conversion. In this work, we employ a novel system, based on cointegrate formation, to isolate gene conversion events associated with crossovers in the nitrogen-fixing bacterium Rhizobium etli. In this system, selection is applied only for cointegrate formation, with gene conversions being detected as unselected events. This minimizes the likelihood of multiple crossovers. To track the extent and architecture of gene conversions, evenly spaced nucleotide changes were made in one of the nitrogenase structural genes (nifH), introducing unique sites for different restriction endonucleases. Our results show that (i) crossover events were almost invariably accompanied by a gene conversion event occurring nearby; (ii) gene conversion events ranged in size from 150 bp to 800 bp; (iii) gene conversion events displayed a strong bias, favoring the preservation of incoming sequences; (iv) even small amounts of sequence divergence had a strong effect on recombination frequency; and (v) the MutS mismatch repair system plays an important role in determining the length of gene conversion segments. A detailed analysis of the architecture of the conversion events suggests that multiple crossovers are an unlikely alternative for their generation. Our results are better explained as the product of true gene conversions occurring under the double-strand break repair model for recombination.
Bacterial Proteins↗
Gene conversions in the horse alpha-globin gene complex.
The sequences of the linked alpha 2- and alpha 1-globin genes of the equine BI and BII haplotypes are greater than 99% identical within a 1.2-kb region extending from approximately 75 bp upstream of the putative cap site to a point approximately 150 bp 3' to the poly A addition signal. Differences between the alpha 2 and alpha 1 genes that are common to both haplotypes indicate that a major gene conversion occurred approximately 12 Myr ago and that this has been followed by shorter, more localized, conversions. Interhaplotype (allelic) comparisons at the alpha loci suggest that the BI and BII haplotypes have probably existed independently greater than or equal to 0.5 Myr and that the alpha 1 genes may have undergone a recent interchromosomal gene conversion.
Animals↗
Contribution of gene conversion in the evolution of the human beta-like globin gene family.
Gene conversion is referred to as one of two types of mechanisms known to act on gene families, mainly to maintain their sequence homogeneity or, in certain cases, to produce sequence diversity. The concept of gene conversion was established 20 years ago by researchers working with fungi. A few years later, gene conversion was also observed in the human genome, i.e. the gamma-globin locus. The aim of this article is to emphasize the role of genetic recombination, particularly of gene conversion, in the evolution of the human beta-like globin genes and further to summarize its contribution to the convergent evolution of the fetal globin genes. Finally, this article attempts to re-examine the origin and spread of specific mutations of the beta-globin cluster, such as the sickle cell or beta-thalassemia mutations, on the basis of repeated gene conversion events.
Animals↗
RAG-2 expression is not essential for chicken immunoglobulin gene conversion.
Chicken B cells diversify their immunoglobulin genes by gene conversion in the bursa of Fabricius. The avian leukosis virus-induced B-cell line DT40 continues to diversify its immunoglobulin light chain locus by gene conversion during in vitro passage. Since a variable(diversity)joining recombination-activating gene, RAG-2, is specifically expressed in chicken B cells undergoing immunoglobulin gene conversion, it has been suggested that RAG-2 may be involved in the immunoglobulin gene conversion process. We previously reported high ratios of targeted to random integration after transfection of genomic DNA constructs into DT40. This allows us to easily investigate the function of a gene product by gene disruption. We show here that subclones of DT40 maintain the ability to diversify their immunoglobulin light chain locus by gene conversion even after both copies of the RAG-2 coding regions are deleted. These results demonstrate that the RAG-2 product is not required for gene conversion activity in the immunoglobulin light chain locus.
Animals↗
The expected number of alleles in a gene conversion model with mutation.
Gene conversions and mutations affect the number of different alleles in a population as it evolves. Here these effects are studied for a sample of r individuals represented by one chromosome, each with n loci. The long-term evolution of the sample is modelled with the coalescent. Gene conversions can only occur within a chromosome between a pair of loci. Recombination is not included in the model. Mutations occur according to the infinitely many alleles model. A new expression for the expected number of alleles is derived using the Backward time approach. It is then possible to simulate the expectation for various sample paths. The new estimator is computationally inexpensive and has a lower variance than the conventional, forward time, approximation by simulation.
Alleles↗
Recombination within the human embryonic xi-globin locus: a common xi-xi chromosome produced by gene conversion of the psi xi gene.
The duplicated human embryonic alpha-like globin genes encode a 5' functional zeta (xi 2) gene and a highly homologous pseudogene (psi xi 1). We have identified chromosomes with a xi 2-xi 1 rather than a xi 2-psi xi 1 arrangement by genomic mapping and oligonucleotide analysis. The DNA sequence of a cloned downstream xi-like gene provides direct evidence for the conversion of a psi xi 1----xi 1 gene, by a xi 2 gene. We present data suggesting that this gene conversion, which removed the only identifiable inactivating mutation in the psi xi 1 gene, was an interchromosomal event. The xi 2-xi 1 arrangement is common in all eight populations studied representing a previously undescribed type of polymorphism between individuals. Stable mRNA transcripts from the converted gene are absent at 16-20 weeks of gestation when transcripts from the xi 2 gene are readily detectable.
Alleles↗
Codon-usage bias versus gene conversion in the evolution of yeast duplicate genes.
Many Saccharomyces cerevisiae duplicate genes that were derived from an ancient whole-genome duplication (WGD) unexpectedly show a small synonymous divergence (K(S)), a higher sequence similarity to each other than to orthologues in Saccharomyces bayanus, or slow evolution compared with the orthologue in Kluyveromyces waltii, a non-WGD species. This decelerated evolution was attributed to gene conversion between duplicates. Using approximately 300 WGD gene pairs in four species and their orthologues in non-WGD species, we show that codon-usage bias and protein-sequence conservation are two important causes for decelerated evolution of duplicate genes, whereas gene conversion is effective only in the presence of strong codon-usage bias or protein-sequence conservation. Furthermore, we find that change in mutation pattern or in tDNA copy number changed codon-usage bias and increased the K(S) distance between K. waltii and S. cerevisiae. Intriguingly, some proteins showed fast evolution before the radiation of WGD species but little or no sequence divergence between orthologues and paralogues thereafter, indicating that functional conservation after the radiation may also be responsible for decelerated evolution in duplicates.
Codon↗
Independent gene evolution in the potato actin gene family demonstrated by phylogenetic procedures for resolving gene conversions and the phylogeny of angiosperm actin genes.
Nine different actin DNA sequences were isolated from the common potato, Solanum tuberosum, and the nucleotide sequence of five actin loci and of two allelic variants are presented. Unlike the wide variation in intron position among animal actin genes, the potato actin genes have three introns situated in the same positions as reported for all other angiosperm actin genes. Using a novel combination of analytical procedures (G-test and compatibility analysis), we could not find evidence of frequent large or small nonreciprocal exchanges of genetic material between the sequenced loci, although there were a few candidates. Resolution of such gene conversion events and the quantification of independence of gene evolution in multigene families is critical to the inference of phylogenetic relationships. Comparison with actin genes in other angiosperm species suggests that the actin multigene family can be divided into a number of subfamilies, evolved by descent rather than gene conversion, which are of possible functional origin, with one major subfamily diversification occurring before the divergence of monocots and dicots. The silent rate of nucleotide substitution was estimated to be similar to that suggested for a number of other plant nuclear genes, whereas the replacement rate was extremely slow, suggestive of selective constraints.
Actins↗
Gene conversion and concerted evolution in bacterial genomes.
Gene conversion is defined as the non-reciprocal transfer of information between homologous sequences. Despite methodological problems to establish non-reciprocity, gene conversion has been demonstrated in a wide variety of bacteria. Besides examples of high-frequency reversion of mutations in repeated genes, gene conversion in bacterial genomes has been implicated in concerted evolution of multigene families. Gene conversion also has a prime importance in the generation of antigenic variation, an interesting mechanism whereby some bacterial pathogens are able to avoid the host immune system. In this review, we analyze examples of bacterial gene conversion (some of them spawned from the current genomic revolution), as well as the molecular models that explain gene conversion and its association with crossovers.
Antigenic Variation↗
Gene conversion and the evolution of three leucine-rich repeat gene families in Arabidopsis thaliana.
The high number of duplicated genes in plant genomes provides a potential template for gene conversion and unequal crossing-over. Within a gene family these two processes can render all members homogeneous or generate diversity by reassorting variants among paralogs. The latter is especially feasible in families where gene diversity confers a selective advantage and thus conversion events are likely to be retained. Consequently, the most complete record of gene conversion is expected to be most evident in gene families commonly subjected to positive selection. Here, we describe the extent and characteristics of gene conversion and unequal crossing-over in the coding and noncoding regions of nucleotide-binding site leucine-rich repeat (NBS-LRR), receptor-like kinases (RLK), and receptor-like proteins (RLP) in the plant Arabidopsis thaliana. Members of these three gene families are associated with disease resistance and their pathogen-recognition domain is a documented target of positive selection. Our bioinformatic approach to study the major family features that may influence gene conversion revealed that in these families there is a significant association between the occurrence of gene conversion and high levels of sequence similarity, close physical clustering, gene orientation, and recombination rate. We discuss these results in the context of the overlap between gene conversion and positive selection during the evolutionary expansion of the NBS-LRR, RLK, and RLP gene families.
Arabidopsis↗
Gene conversion in avian mesotocin and vasotocin genes: a recurrent mechanism linking two neurohypophysial precursor lineages?
Amino acid sequences of the first half of MSEL- and VLDV-neurophysins from goose and chicken have been determined. Identical substitutions in positions 17, 18, 35, 36 and 41 of both neurophysins of a given species when compared with their mammalian counterparts suggest a gene conversion between vasotocin--MSEL-neurophysin and mesotocin--VLDV-neurophysin genes. This event, which has already been observed for three mammalian species, seems recurrent and would link the evolution of the two neurohypophysial hormone precursors.
Amino Acid Sequence↗