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Biology subjects

Le, H. P.

Publications and source records attributed to Le, H. P..

2 recordsLinked to original sources

Historical plant embryos as alternative sources of ancient DNA for whole genome sequencing

Natural history and agricultural collections, which contain hundreds of millions of specimens classified in terms of time, space, and taxonomy, are valuable resources for diverse fields of research. Since the first success of ancient DNA (aDNA) isolation in the 1980s, these repositories, including herbaria for plants, have been intensively used to support studies in taxonomy, macroevolution, and genetic responses to anthropogenic activities over the past centuries. Two major challenges of aDNA research are environmental contamination and DNA degradation. For herbarium specimens, aDNA is usually extracted from leaf samples. It is highly fragmented (typically length of 50 to 100 bp) with a higher breakdown rate than that in most bone remains. To optimise the amount of data retrieved and minimise destructive sampling, we isolated DNA from an unconventional plant tissue type - seed embryos. We carried out whole-genome sequencing and compared sequenced DNA quality between embryo and leaf tissue. We evaluated endogenous DNA proportion, median fragment length, damage fraction per site ({lambda}), decay rates, nucleotide misincorporations, and library complexity for three species: cultivated rice Oryza sativa, wild rice O. rufipogon, and wild barley Hordeum spontaneum. In O. sativa, embryos exhibited significantly higher endogenous content and median fragment length than leaves, while in O. rufipogon only median fragment length was higher. The superior DNA preservation was likely due to the protective role of the seed husk, which might play an important role in DNA preservation in plants collected in the tropics. By contrast, in temperate H. spontaneum, tissue type had minimal impact on DNA quality. Despite the minuscule size of the embryos, all derived genomic libraries were highly complex, sufficient for deep whole genome sequencing. These results highlight seed embryos as a promising alternative aDNA source for millions of herbarium specimens, and enable effective genomic analyses of other historical plant collections, such as economic botany and anthropological museum collections.

genomics↗

Strategy for unlimited cycles of scarless oligonucleotide directed gene editing in Chlamydomonas reinhardtii

CRISPR/Cas9 gene editing in the model green alga Chlamydomonas reinhardtii relies on the use of selective marker genes to enrich for non-selectable target mutations. This becomes challenging when many sequential modifications are required in a single cell line, as useful markers are limited. Here we demonstrate a cyclical selection process which only requires a single marker gene to identify an almost infinite sequential series of CRISPR-based target gene modifications. The NIA1 (Nit1, NR; nitrate reductase) gene was this selectable marker. In the forward stage of the cycle, a stop codon was engineered into the NIA1 gene at the CRISPR target location. Cells retaining the wild type NIA1 gene were killed by chlorate, while NIA1 knockout mutants survived. In the reverse phase of the cycle, the stop codon engineered into the NIA1 gene during the forward phase was edited back to the wild type sequence. Using nitrate as the sole nitrogen source, here only the reverted wild type cells survived. By using CRISPR to specifically deactivate and reactivate the NIA1 gene, a marker system was established that flipped back and forth between chlorate- and auxotrophic (nitrate) based selection. This provided a scarless cyclical marker system that enabled an indefinite series of CRISPR edits in other, non-selectable genes. Here, we demonstrate that this Sequential CRISPR via Recycling Endogenous Auxotrophic Markers (SCREAM) technology enables an essentially limitless series of genetic modifications to be introduced to a single cell lineage of C. reinhardtii in a fast and efficient manner to complete complex genetic engineering.

plant biology↗