"Genomes from 240 mammalian species reveal what makes the human genome unique"

[T_aquaticus]

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.

Genomes from 240 mammalian species reveal what makes the human genome unique

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.

In another study, Karlsson, Lindblad-Toh, and colleagues used the mammalian genomes to study human traits and diseases. They focused on some of the most conserved single-letter genomic regions uncovered in the first paper and compared them to genetic variants that scientists have previously linked to diseases such as cancer using other methods.

The team found that their annotations of the genome based on evolutionary conservation revealed more connections between genetic variants and their function than the other methods. They also identified mutations that are likely causal in both rare and common diseases including cancer, and showed that using conservation in disease studies could make it easier to find genetic changes that increase risk of disease.

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:

The phyloP scores have three-base periodicity in coding sequence, consistent with the genetic code (62, 63). The Zoonomia phyloP scores are strongly correlated with the codon degeneracy at individual positions. Nondegenerate sites are far more likely to be constrained bases than fourfold degenerate sites (74.1 versus 18.5%).
https://www.science.org/doi/10.1126/science.abn3943

Of course, I wouldn’t mind hearing from @glipsnort since this appears to be a Broad Institute project, at least in part.

[Argon]

In the flip side, the data probably also shows what makes the other 239 mammalian species unique too!

[T_aquaticus]

@Argon

In the flip side, the data probably also shows what makes the other 239 mammalian species unique too!

That is indeed the case. We humans are most curious about ourselves, but they did look at the wider picture of mammalian adaptations.

Zoonomia is the largest comparative genomics resource for mammals produced to date. By aligning genomes for 240 species, we identify bases that, when mutated, are likely to affect fitness and alter disease risk. At least 332 million bases (~10.7%) in the human genome are unusually conserved across species (evolutionarily constrained) relative to neutrally evolving repeats, and 4552 ultraconserved elements are nearly perfectly conserved. Of 101 million significantly constrained single bases, 80% are outside protein-coding exons and half have no functional annotations in the Encyclopedia of DNA Elements (ENCODE) resource. Changes in genes and regulatory elements are associated with exceptional mammalian traits, such as hibernation, that could inform therapeutic development. Earth’s vast and imperiled biodiversity offers distinctive power for identifying genetic variants that affect genome function and organismal phenotypes.
https://www.science.org/doi/10.1126/science.abn3943

They discuss the possible genetic adaptations for smell sensitivity and hibernation which are pretty interesting.

[Terry_Sampson]

@T_aquaticus

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.

• 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 output GenomeWeb.

  • 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-

[T_aquaticus]

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.