Large X-Linked Palindromes Undergo Arm-to-Arm Gene Conversion across Mus Lineages

Abstract Large (>10 kb), nearly identical (>99% nucleotide identity), palindromic sequences are enriched on mammalian sex chromosomes. Primate Y-palindromes undergo high rates of arm-to-arm gene conversion, a proposed mechanism for maintaining their sequence integrity in the absence of X–Y recombination. It is unclear whether X-palindromes, which can freely recombine in females, undergo arm-to-arm gene conversion and, if so, at what rate. We generated high-quality sequence assemblies of Mus molossinus and M. spretus X-palindromic regions and compared them with orthologous M. musculus X-palindromes. Our evolutionary sequence comparisons find evidence of X-palindrome arm-to-arm gene conversion at rates comparable to autosomal allelic gene conversion rates in mice. Mus X-palindromes also carry more derived than ancestral variants between species, suggesting that their sequence is rapidly diverging. We speculate that in addition to maintaining genes’ sequence integrity via sequence homogenization, palindrome arm-to-arm gene conversion may also facilitate rapid sequence divergence.

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Large X-linked palindromes undergo arm-to-arm gene conversion across Mus lineages

10.1101/800185 ◽

2019 ◽

Author(s):

Callie M. Swanepoel ◽

Emma R. Gerlinger ◽

Jacob L. Mueller

Keyword(s):

Gene Conversion ◽

Rapid Evolution ◽

Genetic Evolution ◽

Evolutionary Sequence ◽

Mus Spretus ◽

High Quality ◽

Sequence Comparisons ◽

Allelic Gene ◽

High Quality Sequence ◽

Palindromic Sequences

AbstractLarge (>10kb), nearly-identical (>99% nucleotide identity), palindromic sequences are enriched on mammalian sex chromosomes. Primate Y-palindromes undergo high rates of arm-to-arm gene conversion, a proposed mechanism for maintaining their sequence integrity in the absence of X-Y recombination. It is unclear whether X-palindromes, which can freely recombine in females, undergo arm-to-arm gene conversion and, if so, at what rate. We generated high-quality sequence assemblies of Mus molossinus and Mus spretus X-palindromic regions and compared them to orthologous Mus musculus X-palindromes. Our evolutionary sequence comparisons found evidence of X-palindrome arm-to-arm gene conversion at rates comparable to rates of autosomal allelic gene conversion in mice. Mus X-palindrome genes also exhibit higher than expected sequence diversification, indicating gene conversion may facilitate the rapid evolution of palindrome-associated genes. We conclude that in addition to maintaining genes’ sequence integrity via sequence homogenization, arm-to-arm gene conversion can also rapidly drive genetic evolution via sequence diversification.

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Frequent non-allelic gene conversion on the human lineage and its effect on the divergence of gene duplicates

10.1101/135152 ◽

2017 ◽

Author(s):

Arbel Harpak ◽

Xun Lan ◽

Ziyue Gao ◽

Jonathan K. Pritchard

Keyword(s):

Gene Conversion ◽

Genetic Diseases ◽

Sequence Divergence ◽

Duplicate Gene ◽

Gene Families ◽

Sequence Evolution ◽

Donor Region ◽

Allelic Gene ◽

Order Of Magnitude ◽

Gene Duplicates

AbstractGene conversion is the copying of genetic sequence from a “donor” region to an “acceptor”. In non-allelic gene conversion (NAGC), the donor and the acceptor are at distinct genetic loci. Despite the role NAGC plays in various genetic diseases and the concerted evolution of gene families, the parameters that govern NAGC are not well-characterized. Here, we survey duplicate gene families and identify converted tracts in 46% of them. These conversions reflect a large GC-bias of NAGC. We develop a sequence evolution model that leverages substantially more information in duplicate sequences than used by previous methods and use it to estimate the parameters that govern NAGC in humans: a mean converted tract length of 250bp and a probability of 2.5×10−7per generation for a nucleotide to be converted (an order of magnitude higher than the point mutation rate). Despite this high baseline rate, we show that NAGC slows down as duplicate sequences diverge—until an eventual “escape” of the sequences from its influence. As a result, NAGC has a small average effect on the sequence divergence of duplicates. This work improves our understanding of the NAGC mechanism and the role that it plays in the evolution of gene duplicates.

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Faculty Opinions recommendation of EST analysis of the cnidarian Acropora millepora reveals extensive gene loss and rapid sequence divergence in the model invertebrates.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1016867.201716 ◽

2004 ◽

Author(s):

Patricia Simpson

Keyword(s):

Gene Loss ◽

Sequence Divergence ◽

Acropora Millepora ◽

Est Analysis ◽

Rapid Sequence

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Multiple Heterologies Increase Mitotic Double-Strand Break-Induced Allelic Gene Conversion Tract Lengths in Yeast

Genetics ◽

10.1093/genetics/153.2.665 ◽

1999 ◽

Vol 153 (2) ◽

pp. 665-679 ◽

Cited By ~ 3

Author(s):

Jac A Nickoloff ◽

Douglas B Sweetser ◽

Jennifer A Clikeman ◽

Guru Jot Khalsa ◽

Sarah L Wheeler

Keyword(s):

Gene Conversion ◽

Mismatch Repair ◽

Frameshift Mutation ◽

Strand Break ◽

Double Strand Break ◽

Chromosome Loss ◽

Allelic Gene ◽

Break Induced Replication ◽

Gene Conversion Tract ◽

Conversion Tract

Abstract Spontaneous and double-strand break (DSB)-induced allelic recombination in yeast was investigated in crosses between ura3 heteroalleles inactivated by an HO site and a +1 frameshift mutation, with flanking markers defining a 3.4-kbp interval. In some crosses, nine additional phenotypically silent RFLP mutations were present at ∼100-bp intervals. Increasing heterology from 0.2 to 1% in this interval reduced spontaneous, but not DSB-induced, recombination. For DSB-induced events, 75% were continuous tract gene conversions without a crossover in this interval; discontinuous tracts and conversions associated with a crossover each comprised ∼7% of events, and 10% also converted markers in unbroken alleles. Loss of heterozygosity was seen for all markers centromere distal to the HO site in 50% of products; such loss could reflect gene conversion, break-induced replication, chromosome loss, or G2 crossovers. Using telomere-marked strains we determined that nearly all allelic DSB repair occurs by gene conversion. We further show that most allelic conversion results from mismatch repair of heteroduplex DNA. Interestingly, markers shared between the sparsely and densely marked interval converted at higher rates in the densely marked interval. Thus, the extra markers increased gene conversion tract lengths, which may reflect mismatch repair-induced recombination, or a shift from restoration- to conversion-type repair.

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Evidence of extensive non-allelic gene conversion among LTR elements in the human genome

Scientific Reports ◽

10.1038/srep28710 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 19

Author(s):

Beniamino Trombetta ◽

Gloria Fantini ◽

Eugenia D’Atanasio ◽

Daniele Sellitto ◽

Fulvio Cruciani

Keyword(s):

Human Genome ◽

Gene Conversion ◽

Allelic Gene

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Mechanisms of Recombination between Diverged Sequences in Wild-Type and BLM-Deficient Mouse and Human Cells

Molecular and Cellular Biology ◽

10.1128/mcb.01553-09 ◽

2010 ◽

Vol 30 (8) ◽

pp. 1887-1897 ◽

Cited By ~ 40

Author(s):

Jeannine R. LaRocque ◽

Maria Jasin

Keyword(s):

Gene Conversion ◽

Mammalian Cells ◽

Sequence Divergence ◽

Dna Lesions ◽

Human Cells ◽

Deficient Mouse ◽

Wild Type ◽

Strand Breaks ◽

Major Mechanism ◽

Homeologous Recombination

ABSTRACT Double-strand breaks (DSBs) are particularly deleterious DNA lesions for which cells have developed multiple mechanisms of repair. One major mechanism of DSB repair in mammalian cells is homologous recombination (HR), whereby a homologous donor sequence is used as a template for repair. For this reason, HR repair of DSBs is also being exploited for gene modification in possible therapeutic approaches. HR is sensitive to sequence divergence, such that the cell has developed ways to suppress recombination between diverged (“homeologous”) sequences. In this report, we have examined several aspects of HR between homeologous sequences in mouse and human cells. We found that gene conversion tracts are similar for mouse and human cells and are generally ≤100 bp, even in Msh2 − / − cells which fail to suppress homeologous recombination. Gene conversion tracts are mostly unidirectional, with no observed mutations. Additionally, no alterations were observed in the donor sequences. While both mouse and human cells suppress homeologous recombination, the suppression is substantially less in the transformed human cells, despite similarities in the gene conversion tracts. BLM-deficient mouse and human cells suppress homeologous recombination to a similar extent as wild-type cells, unlike Sgs1-deficient Saccharomyces cerevisiae.

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Induction of recombination between homologous and diverged DNAs by double-strand gaps and breaks and role of mismatch repair

Molecular and Cellular Biology ◽

10.1128/mcb.14.7.4802-4814.1994 ◽

1994 ◽

Vol 14 (7) ◽

pp. 4802-4814

Author(s):

S D Priebe ◽

J Westmoreland ◽

T Nilsson-Tillgren ◽

M A Resnick

Keyword(s):

Gene Conversion ◽

Mismatch Repair ◽

Sequence Divergence ◽

Strand Break ◽

Mismatch Repair Gene ◽

Repair Gene ◽

Heteroduplex Dna ◽

Dna Mismatch ◽

Spontaneous Recombination ◽

The Impact

Sequence homology is expected to influence recombination. To further understand mechanisms of recombination and the impact of reduced homology, we examined recombination during transformation between plasmid-borne DNA flanking a double-strand break (DSB) or gap and its chromosomal homolog. Previous reports have concentrated on spontaneous recombination or initiation by undefined lesions. Sequence divergence of approximately 16% reduced transformation frequencies by at least 10-fold. Gene conversion patterns associated with double-strand gap repair of episomal plasmids or with plasmid integration were analyzed by restriction endonuclease mapping and DNA sequencing. For episomal plasmids carrying homeologous DNA, at least one input end was always preserved beyond 10 bp, whereas for plasmids carrying homologous DNA, both input ends were converted beyond 80 bp in 60% of the transformants. The system allowed the recovery of transformants carrying mixtures of recombinant molecules that might arise if heteroduplex DNA--a presumed recombination intermediate--escapes mismatch repair. Gene conversion involving homologous DNAs frequently involved DNA mismatch repair, directed to a broken strand. A mutation in the PMS1 mismatch repair gene significantly increased the fraction of transformants carrying a mixture of plasmids for homologous DNAs, indicating that PMS1 can participate in DSB-initiated recombination. Since nearly all transformants involving homeologous DNAs carried a single recombinant plasmid in both Pms+ and Pms- strains, stable heteroduplex DNA appears less likely than for homologous DNAs. Regardless of homology, gene conversion does not appear to occur by nucleolytic expansion of a DSB to a gap prior to recombination. The results with homeologous DNAs are consistent with a recombinational repair model that we propose does not require the formation of stable heteroduplex DNA but instead involves other homology-dependent interactions that allow recombination-dependent DNA synthesis.

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Evolution of primate orphan proteins

Biochemical Society Transactions ◽

10.1042/bst0370778 ◽

2009 ◽

Vol 37 (4) ◽

pp. 778-782 ◽

Cited By ~ 17

Author(s):

Macarena Toll-Riera ◽

Robert Castelo ◽

Nicolás Bellora ◽

M. Mar Albà

Keyword(s):

Related Species ◽

Sequence Divergence ◽

Orphan Genes ◽

Closely Related Species ◽

Protein Coding ◽

Rapid Sequence ◽

Adaptive Processes ◽

Mechanisms Of Formation ◽

Novel Protein

Genomes contain a large number of genes that do not have recognizable homologues in other species. These genes, found in only one or a few closely related species, are known as orphan genes. Their limited distribution implies that many of them are probably involved in lineage-specific adaptive processes. One important question that has remained elusive to date is how orphan genes originate. It has been proposed that they might have arisen by gene duplication followed by a period of very rapid sequence divergence, which would have erased any traces of similarity to other evolutionarily related genes. However, this explanation does not seem plausible for genes lacking homologues in very closely related species. In the present article, we review recent efforts to identify the mechanisms of formation of primate orphan genes. These studies reveal an unexpected important role of transposable elements in the formation of novel protein-coding genes in the genomes of primates.

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