Author: Lisa Ercolano and Hannah Jones

An engineer from Johns Hopkins University co-led a team that sequenced the genome of Arabidopsis, the world's most widely used model plant species, in unprecedented detail. So far, the region of the genome—including the centromere, the spindle that guides the chromosomes as the organism grows rapidly from one cell to trillions of cells—is still uncharted territory due to its complex structure. Now, for the first time, researchers have revealed the secrets of Arabidopsis centromeres, revealed their evolutionary process, and provided insights into the paradox that has plagued scientists for decades. Their results were published in the journal Science on November 12.

"In this study, we solved the sequence and structure of the centromere of the most studied plant species in genetics: we use it to understand the genetics of rice, corn, wheat, or tomatoes, etc.," Michael Schatz Said that Bloomberg, Distinguished Professor of Computer Science and Biology at Johns Hopkins University, and Ian Henderson, head of the Plant Genetics and Epigenetics Group at the University of Cambridge, co-led the research. "Although this research was conducted in plants, it must have an impact on human genetics and understanding how human cells grow and divide so precisely." The research also includes co-first author Michael Arug, who recently Together with Schatz, he completed his Ph.D. in the Department of Computer Science at the Johns Hopkins Whiting School of Engineering.

Arabidopsis thaliana is adopted as a model plant because of its short generation time, small size, easy growth and self-pollination to produce prolific seeds. Its rapid life cycle and small genome make it ideal for genetics and mapping the key genes that underpin the features of interest. This small flowering plant that is often found on the roadside has brought many discoveries, and in 2000, it became the first plant to sequence its genome-except for its centromere and telomere (the structure of the end of the chromosome) ) And other complex regions of the genome.

Since then, newer long-read sequencing technologies have been developed, and researchers can view genomes of more than 100,000 nucleotide fragments instead of 100 to 200 nucleotide fragments. This is thanks to the introduction of nanopore sequencing, which measures current when nucleic acid passes through a protein nanopore (a hollow structure inserted into the membrane). When DNA passes through the nanopore, different nucleic acid bases change the current in different ways. The generated electrical signal is then decoded to provide a specific DNA sequence.

The combination of these data and advances in algorithms for assembly reads means that solving the "genome puzzle" is suddenly possible, which was impossible before. Crucially, this also means that the genetic makeup of the centromere can now be explored, because of its challenging structure, which has previously proven to be a dead end.

"It's great to be able to see the centromere for the first time and use it to understand their unusual evolutionary patterns," Henderson said.

For decades, researchers have been trying to understand the paradox of how and why centromeric DNA evolves at an alarming rate while remaining stable enough to perform its work during cell division. In contrast, other ancient parts of the cell tend to evolve very slowly. This study revealed a major change in our understanding of this paradox by revealing the genetic and epigenetic topology of the Arabidopsis centromere.

"It’s amazing that all higher organisms use this process, including all the 10 trillion cells in your body, and the trillions of cells in other animal and plant species. Surprisingly, despite the centromere The function is that the DNA sequence of the centromere has been established and maintained for billions of years; it is actually one of the most variable parts of any genome," Schatz said.

The "map" of the study provides new insights into the "repetitive ecosystem" found in the centromere, revealing the architecture of the repetitive array, which has an impact on how they evolve, etc. The author's model shows that centromeres evolve through cycles of sequence repetition and diversification. The research team plans to use these maps as a basis to understand how and why centromeres evolve so rapidly.

Marker Genetics, Michael Schatz, Genome