Chromosomes have a unique structure. They’re organized into large areas that contain smaller sections, known as topologically associating domains (TADs). Think of TADs as neighborhoods of DNA that group similar sequences together. Inside these neighborhoods, loops form, connecting different parts of the DNA, but this process isn’t random. It requires energy and specific proteins to work.
For example, in complex organisms like humans, a protein called cohesin acts like a lasso, holding the chromatin loop together until it meets another protein, CTCF, which tells it where to stop. This intricate looping system helps regulate gene expression more effectively. One enhancer can influence several genes, while a single gene can be influenced by multiple enhancers, allowing for more complex combinations of genetic activity.
Recent research by Sebé-Pedrós and his team indicates that chromatin looping played a key role in the evolution of multicellular life, distinguishing organisms like cnidarians and ctenophores from simpler, single-celled relatives. These simple eukaryotes include ichthyosporeans, filastereans, and choanoflagellates, which are the closest living relatives of animals.
Using a technique called Micro-C, the researchers mapped how different parts of chromatin are brought together. Micro-C, developed about a decade ago, provides a detailed view of the genome’s three-dimensional organization. This method is particularly valuable for studying species with smaller genomes, as it allows for finer cuts of DNA. The findings reveal that cnidarians and other early multicellular animals have a much more complex genome architecture compared to unicellular organisms—even those with smaller genomes like ctenophores possess thousands of chromatin loops, unlike single-celled organisms.
Tessa Popay from the Salk Institute notes that chromatin looping could be essential for cell specialization in multicellular organisms. Her research shows that this looping might also be crucial for the expression of specific genes linked to cell identity in mammals.
However, scientists still question how cnidarians and ctenophores form these loops. They likely use cohesin proteins similar to mammals, but without CTCF, the exact mechanics remain unclear. Some researchers propose that other proteins may fulfill the same role in these simpler animals.
There’s also uncertainty around the role of enhancers in early metazoans. Some believe enhancers could produce RNA molecules that interact with regulatory systems, similar to what we see in vertebrates today. Yet others, like Sebé-Pedrós, suggest that enhancers in early organisms merely gathered transcription factors, with more structured regulatory systems evolving later.
Experts like Iñaki Ruiz-Trillo emphasize the challenge of understanding the evolution of these organisms, as millions of years have altered their descendants significantly. Genetics played a pivotal role, expanding the genomes of multicellular organisms, even if the number of protein-coding genes remained similar to their unicellular ancestors.
Looking ahead, researchers wish to uncover the “grammar” or rules governing these genetic interactions. There’s a fascinating idea that regulatory innovations may have been hidden within single-celled ancestors, waiting for the right moment to emerge. This raises intriguing questions about the future of evolution: Could new combinations of existing genes lead to even more complex life forms?
For those interested in further research, you can explore studies on genomic regulation from the Weizmann Institute of Science.
