scholarly journals Frequent nonallelic gene conversion on the human lineage and its effect on the divergence of gene duplicates

2017 ◽  
Vol 114 (48) ◽  
pp. 12779-12784 ◽  
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 ◽  
Order Of Magnitude ◽  
Evolution Of Gene Families ◽  
Gene Duplicates

Gene conversion is the copying of a genetic sequence from a “donor” region to an “acceptor.” In nonallelic 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 250 bp and a probability of 2.5×10−7 per 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.

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

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.

scholarly journals Gene Families, Epistasis and the Amino Acid Preferences of Protein Homologs

2019 ◽  
Vol 15 ◽  
pp. 117693431987048
Author(s):  
Evandro Ferrada
Keyword(s):  
Amino Acid ◽  
Genetic Background ◽  
Sequence Divergence ◽  
Gene Families ◽  
Structure And Function ◽  
Sequence Evolution ◽  
Systematic Analysis ◽  
Fitness Effects ◽  
Computational Work ◽  
And Function

In order to preserve structure and function, proteins tend to preferentially conserve amino acids at particular sites along the sequence. Because mutations can affect structure and function, the question arises whether the preference of a protein site for a particular amino acid varies between protein homologs, and to what extent that variation depends on sequence divergence. Answering these questions can help in the development of models of sequence evolution, as well as provide insights on the dependence of the fitness effects of mutations on the genetic background of sequences, a phenomenon known as epistasis. Here, I comment on recent computational work providing a systematic analysis of the extent to which the amino acid preferences of proteins depend on the background mutations of protein homologs.

scholarly journals Gene conversion facilitates the adaptive evolution of self-resistance in highly toxic newts

2021 ◽  
Author(s):  
Kerry L Gendreau ◽  
Angela D Hornsby ◽  
Michael TJ Hague ◽  
Joel W McGlothlin
Keyword(s):  
Gene Conversion ◽  
Gene Families ◽  
Nonsynonymous Substitution ◽  
Extreme Resistance ◽  
Antipredator Defense ◽  
Exon Duplication ◽  
Nonsynonymous Substitution Rate ◽  
Evolution Of Gene Families ◽  
High Concentrations ◽  
Novel Exon

AbstractTarichanewts contain high concentrations of the deadly toxin TTX as an antipredator defense, requiring them to be physiologically resistant to their own toxin. Here, we reconstruct the origins of TTX self-resistance by sequencing the voltage-gated sodium channel (SCNA) gene family, the target of TTX, in newts and related salamanders. We show that extreme resistance in newts consists of a mixture of ancient changes and lineage-specific substitutions and that the nonsynonymous substitution rate is elevated in newts, suggesting positive selection. We also identify a novel exon duplication withinSCN4Aencoding an expressed TTX-binding site. Two resistance-conferring changes within newts appear to have spread via nonallelic gene conversion: in one case, one codon was copied between paralogs, and in the second, multiple substitutions were homogenized between the duplicate exons ofSCN4A. Our results demonstrate that gene conversion can accelerate the coordinated evolution of gene families in response to selection.

scholarly journals Sequence identity in an early chorion multigene family is the result of localized gene conversion.

Genetics ◽  
1991 ◽  
Vol 128 (3) ◽  
pp. 595-606
Author(s):  
B L Hibner ◽  
W D Burke ◽  
T H Eickbush
Keyword(s):  
Nucleotide Sequence ◽  
Gene Conversion ◽  
Nucleotide Sequence Identity ◽  
Early Period ◽  
Gene Families ◽  
Multigene Families ◽  
Coding Regions ◽  
Sequence Identity ◽  
Isolation And Characterization ◽  
Sequence Exchange

Abstract The multigene families that encode the chorion (eggshell) of the silk moth, Bombyx mori, are closely linked on one chromosome. We report here the isolation and characterization of two segments, totaling 102 kb of genomic DNA, containing the genes expressed during the early period of choriogenesis. Most of these early genes can be divided into two multigene families, ErA and ErB, organized into five divergently transcribed ErA/ErB gene pairs. Nucleotide sequence identity in the major coding regions of the ErA genes was 96%, while nucleotide sequence identity for the ErB major coding regions was only 63%. Selection pressure on the encoded proteins cannot explain this difference in the level of sequence conservation between the ErA and ErB gene families, since when only fourfold redundant codon positions are considered, the divergence within the ErA genes is 8%, while the divergence within the ErB genes (corrected for multiple substitutions at the same site) is 110%. The high sequence identity of the ErA major exons can be explained by sequence exchange events similar to gene conversion localized to the major exon of the ErA genes. These gene conversions are correlated with the presence of clustered copies of the nucleotide sequence GGXGGX, encoding paired glycine residues. This sequence has previously been correlated with gradients of gene conversion that extend throughout the coding and noncoding regions of the High-cysteine (Hc) chorion genes of B. mori. We suggest that the difference in the extent of the conversion tracts in these gene families reflects a tendency for these recombination events to become localized over time to the protein encoding regions of the major exons.

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

2010 ◽  
Vol 30 (8) ◽  
pp. 1887-1897 ◽  
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.

High-frequency germ line gene conversion in transgenic mice

1992 ◽  
Vol 12 (6) ◽  
pp. 2545-2552
Author(s):  
J R Murti ◽  
M Bumbulis ◽  
J C Schimenti
Keyword(s):  
Gene Conversion ◽  
Dna Sequences ◽  
High Frequency ◽  
Germ Line ◽  
Gene Families ◽  
Histochemical Staining ◽  
Evolutionary Significance ◽  
Evolutionary Divergence ◽  
Lacz Gene ◽  
Male Gametes

Gene conversion is the nonreciprocal transfer of genetic information between two related genes or DNA sequences. It can influence the evolution of gene families, having the capacity to generate both diversity and homogeneity. The potential evolutionary significance of this process is directly related to its frequency in the germ line. While measurement of meiotic inter- and intrachromosomal gene conversion frequency is routine in fungal systems, it has hitherto been impractical in mammals. We have designed a system for identifying and quantitating germ line gene conversion in mice by analyzing transgenic male gametes for a contrived recombination event. Spermatids which undergo the designed intrachromosomal gene conversion produce functional beta-galactosidase (encoded by the lacZ gene), which is visualized by histochemical staining. We observed a high incidence of lacZ-positive spermatids (approximately 2%), which were produced by a combination of meiotic and mitotic conversion events. These results demonstrate that gene conversion in mice is an active recombinational process leading to nonparental gametic haplotypes. This high frequency of intrachromosomal gene conversion seems incompatible with the evolutionary divergence of newly duplicated genes. Hence, a process may exist to uncouple gene pairs from frequent conversion-mediated homogenization.

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

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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