I stumbled across a pretty cool press release for a set of papers that compared the genomes of 240 mammal species, including humans. It’s from 2023, so I’m a bit late to the party, but it’s still a pretty amazing set of studies that were all released at the same time.
One of the major tools used by these studies is evolutionary constraint, the fact that functionally important stretches of DNA will be subject to purifying selection which reduces the number of mutations that accumulate over time. These signatures of sequence conservation could be important for a whole range of findings, from understanding specific phenotypes in mammalian species to possible targets for cancer research and human genetic disease in general.
If you venture into the peer reviewed papers linked at the bottom of the press release you can learn more about the specifics, as well as example after example of the types of patterns that we would expect to see from shared mammalian ancestry and evolution. For example:
Of course, I wouldn’t mind hearing from @glipsnort since this appears to be a Broad Institute project, at least in part.
As one who finds himself increasingly late to parties, I took it upon myself to see what else, if anything I have missed, so I asked Chat GPT: "Are there any updates to: “Genomes from 240 mammalian species reveal what makes the human genome unique”?
Response:
As of August 5, 2025, there have been no comparable large-scale follow-up publications (e.g. involving >240 mammal genomes) that significantly expand or revise the original findings:
A web search reveals no major new Zoonomia papers or similarly scaled comparative genomics efforts published after the 2023 Science series.
News coverage and institutional updates around Karolinska and UMass highlight that the 11‑paper Zoonomia series remains the core outputGenomeWeb.
GenomeWeb and related outlets continue to reflect on the 2023 data as the most comprehensive mammalian alignment to date (~4% of all mammals) with no newer datasets surpassing it GenomeWeb.
Broader context: Human Pangenome & related efforts
While the Zoonomia Project focused on mammalian diversity broadly, other initiatives have advanced our understanding of human genomic variation:
The Human Pangenome Reference Consortium (HPRC) released a draft human pangenome in 2023. It includes 47 phased, diploid assemblies from diverse ancestries, capturing an additional ~119 million bases and over 1,100 gene duplications beyond the GRCh38 reference—with improvements in variant discovery and representation of structural diversity GenomeWeb+6UMass Chan Medical School+6NSF - National Science Foundation+6.
That work addresses within-species human variation, while Zoonomia targets between-species comparisons—so they complement each other, but they’re not direct follow-
Skimming through Google Scholar search for “Zoonomia” and “after 2024” turns up several papers that take the findings of the original batch of 2023 papers and try to apply them to human disease, amongst other topics.
My guess is that the database won’t be expanded upon until there is a need, such as the discovery of interesting adaptations in a specific lineage that could be better understood with better coverage than what is in the current Zoonomia database.
Another interesting aspect is the data analysis pipeline that was developed alongside the sequence database. Most notably, the machine learning tools that were developed to better understand gene regulatory networks. I briefly dipped my toe into gene regulation networks, and I can affirm that the human brain just wasn’t made to grok these types of expansive datasets.
Another interesting finding is the detection of both the initial divergence of the placental lineages as supercontinents broke up during the late Cretaceous, and the rapid diversification of placental mammals after the K/Pg extinction event. This is yet another example of multiple lines of evidence (fossils, radiometric dating, tectonic movement, and molecular clocks) correlating with one another.
A lot of good stuff there. I know a number of the authors (including having a couple of ex-members of the project in my evolution reading group), but I can’t say that I’ve ever read the papers in depth. (Partly because I’m an infectious disease guy now and this is no longer my specialty, and partly because I’m moving gradually toward retirement – I leave most keeping up with the literature to the younguns.)
Criticisms:
Completeness of the human genome:
The human genome sequence is not entirely complete, and some parts remain challenging to sequence due to repetitive DNA. This impacts the accuracy and completeness of the comparisons made.
Oversimplification of genome function:
While the study identifies conserved and deleted regions, it may not fully capture the complex interplay between genes, regulatory elements, and the environment in shaping traits.
Potential for misinterpretation of deletions:
The study suggests that some deletions are beneficial, but it’s important to acknowledge that they may also have negative consequences in different contexts or for other traits.
Generalizability and ecological context:
The study primarily focuses on a limited set of mammalian species, and the findings may not be directly generalizable to all mammals or other species.
So peer reviewed or not, that doesnt mean the paper is correct, all it suggests is that it aligns with the presuppositions of the peers
You are so eager to seize on anything to buttress your presuppositions, that you are allowing AI churn to make you look ridiculous. If you do not vet your sources, that’s on you, not Chat GPT.
Don’t bother Adam, because yes, it is all there. Chromosome to Chromosome. All the repetitive DNA and all the challenging sequences. No missing bits. Entirely complete.
And in the past few years, dozens of other species had been sequenced T2T *telomere to telomere", as well.
I have clicked on this link and read the article over and over again. But I cannot find anything answering the promise of the title. It is beginning to look like outright deception. I see absolutely nothing about anything unique discovered in the human genome by this study!!!
I like to accumulate such discoveries because they are very interesting to me. But from this I am not getting anything to add to my list.
sweat cooling system making us the best persistent hunters
cooking our food which made the acquisition of nutrients more efficient giving us more time for other pursuits.
upright locomotion freeing the hands for the development of language followed by adaptations to the use of verbal language freeing up the hands for weapons and tools
The intro of the second of these was the most promising to me…
Human accelerated regions (HARs) are evolutionarily conserved sequences that acquired an unexpectedly high number of nucleotide substitutions in the human genome since divergence from our common ancestor with chimpanzees. Prior work has established that many HARs are gene regulatory enhancers that function during embryonic development, particularly in neurodevelopment, and that most HARs show signatures of positive selection. However, the events that caused the sudden change in selective pressures on HARs remain a mystery.
Not too difficult to speculate since the other developments in my list above are all likely candidates for a positive selection for improved neurodevelopment, but especially the last of them (language and the increased use of tools).
Isn’t the real mystery why there is an unexpectedly high number of nucleotide substitutions? Could that come from a singular genetic mutation of some sort? I remember reading that some parasites can cause genetic mutation. Can viruses do this? With the way they hijack a cell’s reproductive system this seems possible to me, but I would expect you to know better.
Regrettably, the molecular clock claims of matching up with geology are problematic, going back to the original publications. Continents are moving all the time. Sea level is going up and down all the time. Countless other things are going on at the same time. Actual evidence that a molecular date has anything to do with particular environmental events is generally lacking; it’s usually a hand-waving reference to famous geological events.
The exact quality of human and other genome data is a challenge for some types of questions. For example, if you want to ask what the percent similarity in DNA is between humans and chimps, you need to specify exactly how you are calculating similarity. Is it the percent of DNA that has a close match somewhere? How do you count when the chimp has 10 copies of a particular DNA sequence and we have 12? What about when chimps have between 10 and 12 copies and we have 11? So the exact percentage depends on how you measure.
But such quibbling about details of how you measure can’t be honestly used to claim that our DNA is not closely similar to chimps. Evolution is not a steady pattern of every bit of DNA changing at the same rate. When genes are duplicated, different descendants can inherit in complex patterns. A modest number of genes in humans more closely resemble gorilla than chimp. Yet overall, our genome closely resembles that of chimps, with increasing differences as you get to more distantly related organisms. It is inconsistent to make a big deal about the structure of the genome as indicating design while claiming that the similarities between the genomes are not significant.
From my limited understanding of population genetics, that’s the expected signature from positive selection, so I don’t think it is a mystery. I highly doubt a higher mutation rate is needed to explain this. The actual mystery is the environmental conditions that selected for these mutations. Why were they selected for in the human lineage but not the chimp lineage? It could be due to contingent changes that allowed for selection in genes related to neurodevelopment (e.g. the evolution of bipedality), but these types of selection pressures are often difficult to ferret out.
I haven’t seen anything in those papers on baldness, but there is a lot of research on the topic. It’s worth noting that other primates have the same condition (e.g. macaques and chimps). They have discovered many candidate genes, but it appears they haven’t completely figured out the entire genetic map for male pattern baldness, mostly due to it being a condition caused by many different genes (i.e. polygenic). One interesting study:
It can be either. I don’t follow HAR research much anymore since I don’t work on humans, but the last I’d heard, there was good evidence that some HARs were caused by directional selection and that some were caused by an elevated mutation rate, specifically mutations caused by the presence of recombination hotspots in the HAR.
Broader context: Human Pangenome & related efforts