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

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.

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

2020 ◽  
Vol 37 (7) ◽  
pp. 1979-1985 ◽  
Author(s):  
Callie M Swanepoel ◽  
Emma R Gerlinger ◽  
Jacob L Mueller
Keyword(s):  
Gene Conversion ◽  
Sequence Divergence ◽  
Evolutionary Sequence ◽  
High Quality ◽  
Sequence Comparisons ◽  
Rapid Sequence ◽  
Conversion Rates ◽  
Allelic Gene ◽  
High Quality Sequence ◽  
Palindromic Sequences

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.

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

Genetics ◽  
1999 ◽  
Vol 153 (2) ◽  
pp. 665-679 ◽  
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.

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

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Beniamino Trombetta ◽  
Gloria Fantini ◽  
Eugenia D’Atanasio ◽  
Daniele Sellitto ◽  
Fulvio Cruciani
Keyword(s):  
Human Genome ◽  
Gene Conversion ◽  
Allelic Gene

scholarly journals Embryonic Expression and Evolution of Duplicated E-Protein Genes in Xenopus laevis: Parallels With Ancestral E-Protein Genes

Genetics ◽  
1997 ◽  
Vol 146 (1) ◽  
pp. 345-353
Author(s):  
Daniel H Shah ◽  
Toomas Neuman ◽  
Mauricio X Zuber
Keyword(s):  
Xenopus Laevis ◽  
Expression Patterns ◽  
Rapid Evolution ◽  
E Proteins ◽  
Sequence Comparisons ◽  
Gene Expansion ◽  
Helix Loop Helix ◽  
E Protein ◽  
Chordate Evolution ◽  
Clawed Frog

E-proteins comprise a subfamily of helix-loop-helix transcription factors that have been identified in arthropods and several chordate taxa. In mammals, there are three classes of E-protein genes (E2A, E2-2, and HEB) that encode related, and often interchangeable, gene products. We have determined that the clawed frog Xenopus laevis contains twice the number of transcriptionally active E-protein genes when compared with other vertebrate species. Based upon genomic Southern blots and nucleotide sequence comparisons, it is likely that the additional X. laevis genes arose from tetraploidization. During embryogenesis, XE2A (homologue of mammalian E2A) transcripts were broadly expressed in anterior and posterior regions of the embryo while homologues of E2-2 (XE2.2) and HEB (XE1.2) appeared in vertebrate-specific structures including the pineal gland, olfactory bulb, and brachial arches. A phylogenetic analysis of these genes and other known metazoan E-proteins suggests that there were two periods of marked E-protein gene expansion; one that predated the radiation of vertebrates, and the other that coincided with Xenopus tetraploidization. Both of these periods were characterized by the rapid evolution of E2-2 and HEB-class genes, but not of E2A. We propose that the former genes acquired new or specialized roles during early chordate evolution and also more recently in Xenopus, as reflected by the stereotypic expression patterns of these genes during X. laevis development.

scholarly journals Evaluating cost-effectiveness in the management of neuroendocrine neoplasms

2020 ◽  
Author(s):  
B. E. White ◽  
R. Mujica-Mota ◽  
T. Snowsill ◽  
E. M. Gamper ◽  
R. Srirajaskanthan ◽  
...  
Keyword(s):  
Health Economic ◽  
Cost Effectiveness ◽  
Pharmacological Treatment ◽  
Rapid Evolution ◽  
Best Supportive Care ◽  
Cochrane Library ◽  
Economic Evaluations ◽  
Neuroendocrine Neoplasms ◽  
High Quality ◽  
Health Economic Analysis

Abstract The rapid evolution of novel, costly therapies for neuroendocrine neoplasia (NEN) warrants formal high-quality cost-effectiveness evaluation. Costs of individual investigations and therapies are high; and examples are presented. We aimed to review the last ten years of standalone health economic evaluations in NEN. Comparing to published standards, EMBASE, Cochrane library, Database of Abstracts of Reviews of Effects (DARE), NHS Economic Evaluation Database and the Health Technology Assessment (HTA) Database were searched for health economic evaluations (HEEs) in NEN published between 2010 and October 2019. Of 12 economic evaluations, 11 considered exclusively pharmacological treatment (3 studies of SSAs, 7 studies of sunitinib, everolimus and/or 177Lu-DOTATATE and 1 study of telotristat ethyl) and 1 compared surgery with intraarterial therapy. 7 studies of pharmacological treatment had placebo or best supportive care as the only comparator. There remains a paucity of economic evaluations in NEN with the majority industry funded. Most HEEs reviewed did not meet published health economic criteria used to assess quality. Lack of cost data collected from patient populations remains a significant factor in HEEs where clinical expert opinion is still often substituted. Further research utilizing high-quality effectiveness data and rigorous applied health economic analysis is needed.

Evolutionary sequence comparisons using high-density oligonucleotide arrays

1998 ◽  
Vol 18 (2) ◽  
pp. 155-158 ◽  
Author(s):  
Joseph G. Hacia ◽  
Wojciech Makalowski ◽  
Keith Edgemon ◽  
Michael R. Erdos ◽  
Christiane M. Robbins ◽  
...  
Keyword(s):  
High Density ◽  
Evolutionary Sequence ◽  
Sequence Comparisons ◽  
Oligonucleotide Arrays

scholarly journals Gene Conversion amongst Alu SINE Elements

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 905
Author(s):  
Liliya Doronina ◽  
Olga Reising ◽  
Jürgen Schmitz
Keyword(s):  
Gene Conversion ◽  
Ribosomal Rna ◽  
Homologous Sequence ◽  
Systematic Screening ◽  
Short Interspersed Elements ◽  
Binding Domains ◽  
Allelic Gene ◽  
New Strategy ◽  
Integrative Process ◽  
Clear Cases

The process of non-allelic gene conversion acts on homologous sequences during recombination, replacing parts of one with the other to make them uniform. Such concerted evolution is best described as paralogous ribosomal RNA gene unification that serves to preserve the essential house-keeping functions of the converted genes. Transposed elements (TE), especially Alu short interspersed elements (SINE) that have more than a million copies in primate genomes, are a significant source of homologous units and a verified target of gene conversion. The consequences of such a recombination-based process are diverse, including multiplications of functional TE internal binding domains and, for evolutionists, confusing divergent annotations of orthologous transposable elements in related species. We systematically extracted and compared 68,097 Alu insertions in various primates looking for potential events of TE gene conversion and discovered 98 clear cases of Alu–Alu gene conversion, including 64 cases for which the direction of conversion was identified (e.g., AluS conversion to AluY). Gene conversion also does not necessarily affect the entire homologous sequence, and we detected 69 cases of partial gene conversion that resulted in virtual hybrids of two elements. Phylogenetic screening of gene-converted Alus revealed three clear hotspots of the process in the ancestors of Catarrhini, Hominoidea, and gibbons. In general, our systematic screening of orthologous primate loci for gene-converted TEs provides a new strategy and view of a post-integrative process that changes the identities of such elements.

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