ESPE Yearbook of Paediatric Endocrinology

In Brief: The authors of this large international project describe the generation of ‘Zoonomia’, which is a large comparative genomics resource covering 240 different mammalian species. Among their many findings, the authors use this resource to: i) document the vast range of biodiversity on earth, ii) identify 3.6 million genomic sites that are perfectly conserved across species, indicating genes and regulatory regions that are likely essential for mammalian survival, iii) identify genes and regulatory elements that likely underlie species-distinct mammalian traits, such as olfaction, temperature responses, hibernation, immunity and other adaptations to the environment.

Comment: This work documents and celebrates the huge diversity among mammalian species, with important insights into the genes and regulatory regions that are essential across all species, and those that have allowed different species to evolve distinct functions to survival and adapt to different circumstances.

91% of the human genome aligns to at least five other species, and 11% aligns to ≥95% (≥228) of all studied species. These 11% most ‘constrained’ genes are enriched for core molecular processes, such as post-transcriptional regulation (e.g. mRNA processing) and embryonic development (e.g. cell–cell signaling by wnt). By contrast, genes that are most diverse across species are those that regulate interactions with the environment, including innate and adaptive immune responses, skin development, smell, and taste – this finding illustrates the powerful evolutionary processes that enable species to optimally adapt to their environments.

Sometimes, there are important trade-offs. A notable example is absence of the gene CMAH (as occurs in humans and 40 other species, including bats) confers resistance to infection by pathogens that are dependent on the sialic acid metabolite Neu5Gc (e.g. malaria) but increases susceptibility to viruses that bind Neu5Ac, notably severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

A particularly interesting section among the many findings is the mapping of likely genes to distinct mammalian traits. Olfactory abilities vary hugely between species. Rodents have the most olfactory receptor genes. Cetaceans (whales and dolphins) have the fewest. 22 species are deep hibernators – they are able to lower their core body temperature <18 °C for prolonged periods. Efficient degradation of damaged mitochondria appears to allow metabolic depression during hibernation. The authors explain that understanding the processes of hibernation, as well as cellular recovery from cooling and rewarming, could inform healthcare in critical settings, as well as a possible future ‘Sci-fi’ mechanism to enable humans to hibernate during long-distance spaceflight!

Biodiversity is in peril, largely due to human expansion and ‘civilisation’. This paper highlights the importance of studying and protecting biodiversity, which likely has countless lessons to enable new discoveries in human healthcare and survival.