Biomedical subjects

Damon Lisch

Publications and source records attributed to Damon Lisch.

8 recordsLinked to original sources

PubMed2006

Horizontal transfer of a plant transposon.

The majority of well-documented cases of horizontal transfer between higher eukaryotes involve the movement of transposable elements between animals. Surprisingly, although plant genomes often contain vast numbers of these mobile genetic elements, no evidence of horizontal transfer of a nuclear-encoded transposon between plant species has been detected to date. The most mutagenic known plant transposable element system is the Mutator system in maize. Mu-like elements (MULEs) are widespread among plants, and previous analysis has suggested that the distribution of various subgroups of MULEs is patchy, consistent with horizontal transfer. We have sequenced portions of MULE transposons from a number of species of the genus Setaria and compared them to each other and to publicly available databases. A subset of these elements is remarkably similar to a small family of MULEs in rice. A comparison of noncoding and synonymous sequences revealed that the observed similarity is not due to selection at the amino acid level. Given the amount of time separating Setaria and rice, the degree of similarity between these elements excludes the possibility of simple vertical transmission of this class of MULEs. This is the first well-documented example of horizontal transfer of any nuclear-encoded genes between higher plants.

Amino Acid Sequence↗

PubMed2005

The mop1 (mediator of paramutation1) mutant progressively reactivates one of the two genes encoded by the MuDR transposon in maize.

Transposons make up a sizable portion of most genomes, and most organisms have evolved mechanisms to silence them. In maize, silencing of the Mutator family of transposons is associated with methylation of the terminal inverted repeats (TIRs) surrounding the autonomous element and loss of mudrA expression (the transposase) as well as mudrB (a gene involved in insertional activity). We have previously reported that a mutation that suppresses paramutation in maize, mop1, also hypomethylates Mu1 elements and restores somatic activity to silenced MuDR elements. Here, we describe the progressive reactivation of silenced mudrA after several generations in a mop1 background. In mop1 mutants, the TIRA becomes hypomethylated immediately, but mudrA expression and significant somatic reactivation is not observed until silenced MuDR has been exposed to mop1 for several generations. In subsequent generations, individuals that are heterozygous or wild type for the Mop1 allele continue to exhibit hypomethylation at Mu1 and mudrA TIRs as well as somatic activity and high levels of mudrA expression. Thus, mudrA silencing can be progressively and heritably reversed. Conversely, mudrB expression is never restored, its TIR remains methylated, and new insertions of Mu elements are not observed. These data suggest that mudrA and mudrB silencing may be maintained via distinct mechanisms.

Crosses, Genetic↗

PubMed2005

Heritable transposon silencing initiated by a naturally occurring transposon inverted duplication.

It has been suggested that gene silencing evolved as a defense against genomic parasites such as transposons. This idea is based on analysis of mutations that reactivate transposons that are stably silenced: they affect maintenance rather than initiation of silencing. Here we describe the cloning and characterization of a naturally occurring locus able to heritably silence the otherwise highly active MuDR transposon in maize. This locus, Mu killer (Muk), results from the inverted duplication of a partially deleted autonomous MuDR element located at the breakpoint of a genomic deletion. Muk produces a hybrid hairpin transcript that is processed into small RNAs, which are amplified when the target MuDR transcript is present. Muk provides the first example of a naturally occurring transposon derivative capable of initiating the heritable silencing of an active transposon family. Further, transposon-generated inverted duplications may be important for the generation of double-stranded RNAs used in gene silencing.

DNA Transposable Elements↗

PubMed2005

Pack-MULEs: theft on a massive scale.

It has been known for some time that plant transposons can capture and mobilize cellular genes. Recent work by Jiang and coworkers((1)) has revealed that this process has happened on a massive scale. They found that portions of more than 1000 genes in rice have been captured and mobilized by members of the MULE family of transposons. In rice, and perhaps other plants as well, it appears that thousands of genes and portions of genes have been duplicated, transposed and rearranged. These results have fascinating implications for our understanding of the mode and tempo of gene evolution in plants.

Biological Evolution↗

PubMed2003

Mu killer causes the heritable inactivation of the Mutator family of transposable elements in Zea mays.

Mutations in a number of genes responsible for the maintenance of transposon silencing have been reported. However, the initiation of epigenetic silencing of transposable elements is poorly characterized. Here, we report the identification of a single dominant locus, Mu killer (Muk), that acts to silence MuDR, the autonomous regulatory transposon of the Mutator family of transposable elements in maize. Muk results in the methylation of MuDR TIRs and is competent to silence one or several active MuDR elements. Silencing by Muk is not dependent on the position of the MuDR element and occurs gradually during plant development. Transcript levels of the MuDR transposase, mudrA, decrease substantially when Muk is present. The other transcript encoded by MuDR, mudrB, also fails to accumulate in the poly(A) RNA fraction when MuDR and Muk are combined. Additionally, plants undergoing MuDR silencing produce small, mudrA-homologous approximately 26-nt RNAs, suggesting a role for RNA-directed DNA methylation in MuDR silencing. MuDR elements silenced by Muk remain silenced even in plants that do not inherit Muk, suggesting that Muk is required for the initiation of MuDR silencing but not for its maintenance.

DNA Methylation↗

PubMed2002

A mutation that prevents paramutation in maize also reverses Mutator transposon methylation and silencing.

Both paramutation and Mutator (Mu) transposon inactivation involve heritable changes in gene expression without concomitant changes in DNA sequence. The mechanisms by which these shifts in gene activity are achieved are unknown. Here we present evidence that these two phenomena are linked mechanistically. We show that mutation of a gene, modifier of paramutation 1 (mop1), which prevents paramutation at three different loci in maize, can reverse methylation of Mutator elements reliably. In mop1 mutant backgrounds, methylation of nonautonomous Mu elements can be reversed even in the absence of the regulatory MuDR element. Previously silenced MuDR elements are reactivated sporadically after multiple generations of exposure to mop1 mutations. MuDR methylation is separable from MuDR silencing, because removal of methylation does not cause immediate reactivation. The mop1 mutation does not alter the methylation of certain other transposable elements including those just upstream of a paramutable b1 gene. Our results suggest that the mop1 gene acts on a subset of epigenetically regulated sequences in the maize genome and paramutation and Mu element methylation require a common factor, which we hypothesize influences chromatin structure.

Chromatin↗

PubMed2002

Biodiversity (Communications arising): maize transgene results in Mexico are artefacts.

Quist and Chapela's conclusion that the transgenes they claim to have detected in native maize in Oaxaca, Mexico, are predominantly reassorted and inserted into a "diversity of genomic contexts" seems to be based on an artefact arising from the inverse polymerase chain reaction (i-PCR) they used to amplify sequences flanking 35S transgenes from cauliflower mosaic virus (CaMV).

Artifacts↗

PubMed2002

Mutator transposons.

Mutator (Mu) element insertion has become the main way of mutating and cloning maize genes, but we are only beginning to understand how this transposon system is regulated. Mu elements are under tight developmental control and are subject to a form of epigenetic regulation that shares some features with the regulation of paramutable maize genes. Mu-like elements (MULEs) are widespread among angiosperms, and multiple diverged functional variants appear to have coexisted in genomes for long periods. In addition to its utility, the means by which this widespread and highly mutagenic system is held in check should help us to address fundamental issues concerning the stability of genomes.

Amino Acid Sequence↗