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Meddling with Mendel?

Posted by Gareth Ogden, 4 February 2013

Back in 2005, Dr Susan Lolle and her colleagues from Purdue University published a paper on genetic variation in Arabidopsis thaliana in Nature1 that caused quite a stir amongst plant biologists, geneticists and pretty much everyone else in the field of biology. The paper received significant attention from the F1000Prime Faculty, being recommended by 20 Members and becoming the highest scoring paper on the site, as well as subsequently generating some dissent.

A. thaliana is a model organism used in studies of genetic inheritance and plant biology, and a plant that becomes quite familiar to most biology undergraduates in their first years at university. A. thaliana propagates primarily through self fertilisation, and the assumption has always been that plants are genetically uniform. Although this uniformity is useful to the plant biologist and the geneticist, it reduces the genetic diversity of the species. This may not seem like a problem to the non-biologist, but many important agricultural plants are close relatives of A. thaliana and reproduce in the same way, and it brings into question the security of global food sources, as plants can become theoretically less resilient as a consequence of inbreeding.

Arabidopsis thaliana (48°11' N 16°05' E)

That said, Arabidopsis and many agricultural crops have been successfully maintained through inbreeding, which could suggest the existence of underlying mechanisms that counteract the detrimental effects of genetic isolation.

In their 2005 study2, Lolle and colleagues observed frequent reversion of hothead(hth) mutants of A. thaliana, with up to 10% of self-pollinated homozygous mutants found to be carrying a grandparental HTH allele. This anomaly was initially thought to be the result of a template-directed process using cached ancestral RNA, with the instability not limited to the HTH gene, and mutants expressing genome-wide polymorphisms – a theory that turned our traditional understanding of Mendelian inheritance on its head.

Although the data seemed to support the existence of an alternate reserve genome, the paper soon met with significant criticism, with counter theories and calls for more evidence. Contamination3 and out-crossing4 in the experiment were posited, other authors offered theories involving novel genetic phenomena, such as an hth-correcting mechanism dependent on ectopic gene conversion5, a DNA cache that had not yet been discovered6, or even the theory that HTH impairment results in the accumulation of mutagenic compounds, driving the observed mutations at random DNA sites7.

Fast forward to 2013 and Lolle, now at the University of Waterloo is back, and she returns with the support of another research group headed up by Carina Barth formerly at West Virginia University and now with ConRuhr North America. In Lolle’s new paper, entitled “De novo genetic variation revealed in somatic sectors of single Arabidopsis plants8 and published in F1000Research, the group found supporting and complementary evidence for their 2005 study. Their main findings show that Arabidopsis plants are able to produce somatic sectors with varied molecular genotypes. This includes sectors containing genomic insertion sequences generated without a detectable template source, and is consistent with the group’s original theory that the plants have a hidden source of extra-genomic sequence information.

Another article by Barth and colleagues, “The novel Arabidopsis thaliana svt2 suppressor of the ascorbic acid-deficient mutant vtc1-1 exhibits phenotypic and genotypic instability”9, published simultaneously in F1000Research, explores whether novel Arabidopsis svt2 mutants have a mechanism that is able to drive genome fluctuations. The authors observed that mutagenesis of Columbia vtc1-1 mutant seed resulted in the isolation of svt2, with Landsberg-like phenotypic and genotypic characteristics. Additionally, some of the svt-2 lines show transgenerational instability and reverted back to Columbia-like plants in the next generation – a very interesting behaviour indeed for plants that are bred through self-fertilization.

In addition to supporting the original claims made in Lolle’s 2005 work 1 and arguing against the various rebuttals that have been published since then, the combined findings of these two articles could have exciting implications for the field and beyond. The results could alter our basic understanding of genetics, support the development of models to study non-Mendelian inheritance, and provide new insight into the evolution of inbreeding plants. The results are also potentially important to agriculture, and could help us to understand how plants (and, perhaps, other organisms) are able to adapt to environmental stress when ancestral genotypes are better adapted than their progeny.

As is standard for F1000Research articles, the peer review of both of these papers has been conducted post-publication and in the open. To-date, formal reviews have been completed by Andy Pereira (University of Arkansas), Igor Kovalchuk (University of Lethbridge), and David Oppenheimer, (University of Florida), and they can be viewed openly at the bottom of each article online. Both articles have received at least two ‘Approved’ reviews, and will therefore be indexed in the likes of PubMed, Scopus and Embase. All three referees have given full ‘Approved’ statuses for the paper by Lolle’s group while the paper by Barth and colleagues has received a more mixed response with two ‘Approved’ statuses and one ‘Not Approved’ status.

All the reviewers have acknowledged that these papers address a controversial topic, but, particularly in the case of Lolle et al paper, argue in favour of the science and evidence put forward. In his review, Oppenheimer states that the findings obtained by Lolle’s group are unlikely to be the result of contamination “unless the researchers were covered in wt pollen”. He also points out that the inability of other authors 2,3 to reproduce the same results is not an indication that the observed phenomenon doesn’t exist, simply that the other authors were unable to replicate the growth conditions needed to see the effect. Oppenheimer did, however, have a number of concerns with the experimental protocols used in the article by Barth and colleagues, suggesting that the observed anomalies could be the result of seed contamination, and he would like the authors to explicitly state how they guarded against this possibility in order to properly assess the conclusions being drawn.

Both authors will now have the opportunity to address the comments and suggestions raised during the open peer review process and they will be able to modify their articles accordingly, republishing a ‘Version 2′ if they think this is appropriate.

Although it is still too early to assess the full impact of this research, the findings published in these new papers could lead to promising developments for coping with climate change and its potential consequences for global food security, so watch this space.

References

  1. Lolle, Victor, Young et al: Genome-wide non-Mendelian inheritance of extra-genomic information in Arabidopsis. Nature (2005) 434:505-9
  2. Lolle, Victor, Young et al: Genome-wide non-Mendelian inheritance of extra-genomic information in Arabidopsis. Nature (2005) 434:505-9
  3. Peng, Chan, Shah et al: Plant genetics: Increased outcrossing in hothead mutants. Nature (2006) 443, E8
  4. Mercier, Jolivet, Vignard et al: Outcrossing as an explanation of the apparent unconventional genetic behavior of Arabidopsis thaliana hth mutanst. Genetics (2008) 180:2295-2297
  5. Chaudhury A: Plant genetics: Hothead healer and extragenomic information. Nature (2005) 437:E1-E1
  6. Ray A: Plant genetics: RNA cache or genome trash? Nature (2005) 437:E1-E2
  7. Comai and Cartwright: A toxic mutator and selection alternative to the non-Mendelian RNA cache hypothesis for hothead reversion. Plant Cell (2005) (17)11:2856-8
  8. Hopkins MT, Khalid AM, Chang PC et al. (2013) De novo genetic variation revealed in somatic sectors of single Arabidopsis plants [v1; ref status: indexed, http://f1000r.es/kw] F1000Research 2:5 (doi: 10.3410/f1000research.2-5.v1
  9. Kempinski CF, Crowell SV, Smeeth C et al. (2013) The novel Arabidopsis thaliana svt2 suppressor of the ascorbic acid-deficient mutant vtc1-1 exhibits phenotypic and genotypic instability [v1; ref status: indexed, http://f1000r.es/o2] F1000Research 2:6 (doi: 10.3410/f1000research.2-6.v1

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