Centromeres: what, how and why?

Centromeres may not be part of everyday conversation, but they are fundamental to life. These specialised regions of chromosomes are essential for precise cell division, ensuring each new cell receives the correct genetic information. Without them, cells would struggle to divide properly, leading to genetic instability, a root cause of many diseases, including cancer.

Despite their important role, centromeres come in different types and shapes. In most organisms, centromeres are located at a single specific point on each chromosome, known as a monocentric arrangement. However, some organisms, such as certain plants, insects and even some nematodes, have evolved a different strategy. Instead of a single centromere, their chromosomes are holocentric, meaning the centromere spans the entire chromosome. This adaptation allows these chromosomes to tolerate chromosome breaks and fusions, as any part of the chromosome can act as a spindle attachment site during cell division.

Holocentric chromosomes are particularly intriguing because they reflect an alternative evolutionary solution to the essential process of cell division. Thus, our study on the woodrush, Luzula sylvatica, sought to uncover the unique features of these holocentric chromosomes and understand how they may have evolved from the more common monocentric type in the rush family Juncaceae.

What did we find in rushes?

Through our analysis, discovered that L. sylvatica holocentromeres are largely composed of two satellite repeats, which we named as Lusy1 and Lusy2. These repeats are organized into kilobase-scale, CENH3-positive units interspersed within gene-rich regions. We noted also that some centromeric sites lacked these repeats, which indicates a more complex mechanism of evolution, possibly similar to that of neocentromeres, where new centromeres can be formed in repeat-free regions.

Our study places L. sylvatica within the broader context of repeat-based holocentricity observed in other plants, such as Rhynchospora and Chionographis japonica, where satellite DNA are associated to centromeric regions. We further demonstrate that these sequences may play a role in holocentromere function due to their unique ability to adopt a B-DNA conformation. This structural flexibility could facilitate specific binding sites for centromeric proteins like CENH3, stabilizing kinetochore assembly along the chromosome. The stability of the B-DNA conformation under cellular conditions may also favor a dynamic and modular organization that adapts to different chromosomal regions, contributing to the overall flexibility and resilience of the holocentric structure of Luzula sylvatica.

And in a twist of the story, our comparative genomics analysis with a species from the sister genus Juncus revealed a high degree of synteny between the Luzula and Juncus genomes, despite their estimated 60 million years of divergence. We propose that the holocentromeres of L. sylvatica could have evolved through a multistep process involving initial chromosomal fusions followed by the gradual spread of centromeric proteins like CENH3 and the selective invasion of satellite repeats. This evolutionary pathway could resemble the establishment of neocentromeres in some monocentric species, shedding light on an alternative route to achieving holocentricity.

Figure 1: Hypothetical model of the origin of holocentricity in woodrushes. After several fusions of atypical monocentric whole chromosomes (Juncus type) based on repeats, centromeric domains were initially conserved on the larger chromosomes (hypothetical intermediate state), forming polycentric chromosomes. Subsequently, centromeric domain expansion and genome rearrangement gave rise to the holocentric state. Subsequent colonization of Lusy-type satellites allowed the maintenance of functional centromeres. M monocentric, H holocentric. Divergence time was obtained from the Timetree of Life (https://timetree.org/).

In short, this research highlights the extent of flexibility of holocentromeric structures in species with evolutionarily reorganized chromosomes and underscores the role of repetitive sequences in genome stability, adaptation, and evolution. This and future works on understanding these alternative evolutionary strategies for chromosomal stability will enhances our knowledge of life’s resilience and adaptability in a changing world.