So what’s this all about?
Highlight: A careful examination of the available interspecies comparative data to assess TAD conservation suggests that, while they certainly have some functional conservation, specific TAD structures and locations may not be especially conserved across evolutionary lineages.
Abstract: The notion that topologically associating domains (TADs) are highly conserved across species is prevalent in the field of 3D genomics. However, what exactly is meant by ‘highly conserved’ and what are the actual comparative data that support this notion? To address these questions, we performed a historical review of the relevant literature and retraced numerous citation chains to reveal the primary data that were used as the basis for the widely accepted conclusion that TADs are highly conserved across evolution. A thorough review of the available evidence suggests the answer may be more complex than what is commonly presented.Ittai E. Eres, Yoav Gilad, A TAD Skeptic: Is 3D Genome Topology Conserved?, Trends in Genetics, 2020, ISSN 0168-9525, https://doi.org/10.1016/j.tig.2020.10.009.
One important aspect of 3-D genome structure has to do with the epigenetic modification of proteins called histones that the DNA is wrapped around. A 2011 study showed that a specific type of histone modification had only about a 70% overlap or similarity between humans and chimps.4 Remarkably, another study in 2012 showed that humans had about a 70% similarity for the same feature with mice.5 In other words, humans were as different to mice as they were to chimps for this particular genome conformation metric.
In the Trends in Genetics study, scientists wanted to take a closer look at this evolutionary anomaly to see if it held true for one of the most important features of genome conformation—TAD similarity. They found that in comparing humans and chimps, “only ~43% of TADs conserved [similar] between these species, but across many different parameters (e.g., resolution, window size, genome assembly) and different downstream analysis decisions, no more than 78% of domains and 83% of TAD boundaries were found to be shared between humans and chimpanzees.” This huge evolutionary discrepancy led them to conclude, “In our mind, there is no strong basis for the common and often unchallenged notion that TADs are highly conserved.”Jeffrey P. Tompkins, “3-D Human Genome Radically Different from Chimp” at ICR
Some of us remember when we were 99% chimpanzee… But that is so last decade …
This type of finding makes more sense. If we were really 99% genetically similar to chimpanzees, the logical deduction is that the genome doesn’t tell us much about a life form. Would be nice if it did, right?
Hat tip: Philip Cunningham