Gene Conversion and Evolution of Gene Families: An Overview

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.

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

10.1101/2021.03.25.437018 ◽

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.

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Faculty Opinions recommendation of Dosage sensitivity and the evolution of gene families in yeast.

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

10.3410/f.1014360.195904 ◽

2003 ◽

Author(s):

Eugene Koonin

Keyword(s):

Gene Families ◽

Evolution Of Gene Families ◽

Dosage Sensitivity

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Faculty Opinions recommendation of Dosage sensitivity and the evolution of gene families in yeast.

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

10.3410/f.1014360.193365 ◽

2003 ◽

Author(s):

Anne Osbourn

Keyword(s):

Gene Families ◽

Evolution Of Gene Families ◽

Dosage Sensitivity

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

Genetics ◽

10.1093/genetics/128.3.595 ◽

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.

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High-frequency germ line gene conversion in transgenic mice

Molecular and Cellular Biology ◽

10.1128/mcb.12.6.2545-2552.1992 ◽

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.

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treeWidget: a BioJS component to visualise phylogenetic trees

F1000Research ◽

10.12688/f1000research.3-49.v1 ◽

2014 ◽

Vol 3 ◽

pp. 49 ◽

Cited By ~ 1

Author(s):

Fabian Schreiber

Keyword(s):

Phylogenetic Trees ◽

Protein Domains ◽

Gene Families ◽

Sequence Information ◽

Gene Duplications ◽

Link Type ◽

History Of ◽

Conservation Patterns ◽

Evolution Of Gene Families ◽

The Web

Summary: Phylogenetic trees are widely used to represent the evolution of gene families. As the history of gene families can be complex (including lots of gene duplications), its visualisation can become a difficult task. A good/accurate visualisation of phylogenetic trees - especially on the web - allows easier understanding and interpretation of trees to help to reveal the mechanisms that shape the evolution of a specific set of gene/species. Here, I present treeWidget, a modular BioJS component to visualise phylogenetic trees on the web. Through its modularity, treeWidget can be easily customized to allow the display of sequence information, e.g. protein domains and alignment conservation patterns.Availability: http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.7707

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Evolution of Gene Families: A Clue to Some Problems of Neo-Darwinism

Lecture Notes in Biomathematics - Frontiers in Mathematical Biology ◽

10.1007/978-3-642-50124-1_10 ◽

1994 ◽

pp. 174-185

Author(s):

Tomoko Ohta

Keyword(s):

Gene Families ◽

Evolution Of Gene Families

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Evidence for the Contribution of Point Mutations tovlsE Variation and for Apparent Constraints on the Net Accumulation of Sequence Changes in vlsE during Infection with Lyme Disease Spirochetes

Journal of Bacteriology ◽

10.1128/jb.183.20.5855-5861.2001 ◽

2001 ◽

Vol 183 (20) ◽

pp. 5855-5861 ◽

Cited By ~ 25

Author(s):

Shian-Ying Sung ◽

John V. McDowell ◽

Richard T. Marconi

Keyword(s):

Lyme Disease ◽

Gene Conversion ◽

Sequence Variation ◽

Frameshift Mutation ◽

Point Mutations ◽

Gene Families ◽

Nucleotide Polymorphism ◽

Single Nucleotide ◽

Variable Regions

ABSTRACT In the Lyme disease spirochetes, both the ospE andvlsE gene families have been demonstrated to undergo sequence variation during infection. To further investigate the mechanisms associated with the generation of vls variation, single-nucleotide polymorphism and subsequent DNA sequence analyses were performed on the vlsE gene and its paralog, BBJ51, a related gene with a frameshift mutation. These analyses focused on a series of postinfection clonal populations obtained from mice infected with Borrelia burgdorferi B31MIpc or its clonal derivative, B31MIc53. vlsE, but not BBJ51, was found to undergo sequence changes during infection. Consistent with that reported previously (J.-R. Zhang et al., Cell 89:275–285, 1997) many of the sequence changes appear to have arisen through gene conversion events and to be localized to the variable regions of vlsE. However, analysis of the vlsE nucleotide sequences revealed that some sequence changes were the result of point mutations, as these changes did not have potential contributing sources in thevls cassettes. To determine if sequence changes accumulate in vlsE over long-term infection, thevlsE genes of clonal populations recovered after 7 months of infection in mice were analyzed. While new sequence changes developed, a significant number of these changes resulted in the restoration of the vlsE sequence of the original infecting clone. In addition, we noted that some positions within the variable regions (VR) are stable even though the cassettes possess residues that could contribute to sequence variation through gene conversion. These analyses suggest that the total number of amino acid sequence changes that can be maintained by VlsE levels off during infection. In summary, in this report we demonstrate that the development of point mutations serves as a second mechanism by which vlsE sequence variation can be generated and that the capacity for vlsEvariation, while still significant, is less than previously postulated.

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Duplication of chickendefensin7gene generated by gene conversion and homologous recombination

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1616948113 ◽

2016 ◽

Vol 113 (48) ◽

pp. 13815-13820 ◽

Cited By ~ 9

Author(s):

Mi Ok Lee ◽

Susanne Bornelöv ◽

Leif Andersson ◽

Susan J. Lamont ◽

Junfeng Chen ◽

...

Keyword(s):

Homologous Recombination ◽

Copy Number Variation ◽

Gene Conversion ◽

Copy Number ◽

Computational Prediction ◽

Gene Families ◽

Duplication Event ◽

Promoter Regions ◽

Large Gene ◽

Number Variation

Defensins constitute an evolutionary conserved family of cationic antimicrobial peptides that play a key role in host innate immune responses to infection. Defensin genes generally reside in complex genomic regions that are prone to structural variation, and defensin genes exhibit extensive copy number variation in humans and in other species. Copy number variation of defensin genes was examined in inbred lines of Leghorn and Fayoumi chickens, and a duplication ofdefensin7was discovered in the Fayoumi breed. Analysis of junction sequences confirmed the occurrence of a simple tandem duplication ofdefensin7with sequence identity at the junction, suggesting nonallelic homologous recombination betweendefensin7anddefensin6. The duplication event generated two chimeric promoters that are best explained by gene conversion followed by homologous recombination. Expression ofdefensin7was not elevated in animals with two genes despite both genes being transcribed in the tissues examined. Computational prediction of promoter regions revealed the presence of several putative transcription factor binding sites generated by the duplication event. These data provide insight into the evolution and possible function of large gene families and specifically, the defensins.

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