Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Apr 2;41(4):msae075.
doi: 10.1093/molbev/msae075.

Terrestrial Birth and Body Size Tune UCP1 Functionality in Seals

Michael J Gaudry  1 , Jane Khudyakov  2 , Laura Pirard  3 , Cathy Debier  3 , Daniel Crocker  4 , Paul G Crichton  5 , Martin Jastroch  1
Affiliations

Terrestrial Birth and Body Size Tune UCP1 Functionality in Seals

Michael J Gaudry et al. Mol Biol Evol. .

Abstract

The molecular evolution of the mammalian heater protein UCP1 is a powerful biomarker to understand thermoregulatory strategies during species radiation into extreme climates, such as aquatic life with high thermal conductivity. While fully aquatic mammals lost UCP1, most semiaquatic seals display intact UCP1 genes, apart from large elephant seals. Here, we show that UCP1 thermogenic activity of the small-bodied harbor seal is equally potent compared to terrestrial orthologs, emphasizing its importance for neonatal survival on land. In contrast, elephant seal UCP1 does not display thermogenic activity, not even when translating a repaired or a recently highlighted truncated version. Thus, the thermogenic benefits for neonatal survival during terrestrial birth in semiaquatic pinnipeds maintained evolutionary selection pressure on UCP1 function and were only outweighed by extreme body sizes among elephant seals, fully eliminating UCP1-dependent thermogenesis.

Keywords: UCP1; brown adipose tissue; nonshivering thermogenesis; pinniped; pseudogene.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest We disclose no competing interests.

Figures

Fig. 1.
Fig. 1.
UCP1 transcripts from ex vivo northern elephant seal blubber suggest possible UCP1 variants. a) Phylogeny (modified from Berta et al. 2018 and Yuan et al. 2021) highlighting the loss of UCP1 among fully aquatic mammals (sea cow, whale in blue) and large-bodied terrestrial mammals (elephant, horse, pig in red). The pinniped lineage (walrus, sea lion, gray seal, harbor seal, hawaiian monk seal, weddell seal) is highlighted in purple with northern and southern elephant seals in yellow. Animal silhouettes are public domain from phylopic.org under Creative Commons licenses. b) Expression of UCP1 mRNA in blubber tissue slices from weaned northern elephant seal pups (n = 3) treated with cortisol (Cort), epinephrine (Epi), or both. Different letters denote significant differences (P < 0.05). Box boundaries denote maximum and minimum, and mean (internal line). c) UCP1 alignment highlighting the elephant seal UCP1 frameshift mutation (wtES; red), repaired (rpES), and potentially rescuing truncation (trES; red arrow) put forward by Yuan et al. (2022) with highlighted AA residue substitutions relative to harbor seal (HS) and truncated harbor seal (trHS) UCP1 (cyan). d) UCP1 mRNA expression of transiently transfected HEK293 cells (n = 3) with seal and ferret (F) variants, as well an empty vector control (Emp vec). Error bars denote SEM, and UCP1 Ct values are above each bar. e) Representative western blot of HEK293 cells transfected with seal, ferret, and mouse (M) UCP1 variants, as well an empty vector control. f) Western blot of whole cell lysate (cell) versus isolated mitochondrial fraction (mito) from HEK293 cells transfected with trES UCP1 and an empty vector control.
Fig. 2.
Fig. 2.
a) Cross-species comparison of palmitate-induced (100 µM) OCRs of transfected HEK293 cells confirming that elephant seal UCP1 is not thermogenic. OCRs have been corrected for nonmitochondrial respiration. Data are mean ± SEM. N = 3 to 6 from 3 independent runs. Statistical significances are denoted by independent letters in P < 0.05, one-way ANOVA with Tukey's post hoc test (see supplementary fig. S1, Supplementary Material online, for full respirometric traces). UCP1 variants are abbreviated as mouse (M), ferret (F), harbor seal (HS), truncated harbor seal (trHS), wildtype elephant seal (wtES), repaired elephant seal (rpES), and truncated elephant seal (trES), along with the empty vector control (Emp vec). b) Harbor seal versus repaired elephant seal UCP1 homology structure analyses. N-Terminal truncated AAs are indicated with dashed residues. Compromised elephant seal helix 3 and associated substrate binding region and matrix gate interactions are highlighted in red caused by V126-A127 deletion.
Fig. 3.
Fig. 3.
a) Selection pressure analysis of UCP1 coding sequences among pinniped species. Global selection pressures have been calculated for background (black; non-elephant seal) branches with intact UCP1 genes and foreground (yellow; elephant seal) branches displaying inactivating mutations. b) Log-transformed birth weights of eutherian species with intact UCP1 genes versus those that display UCP1 pseudogenes. Black dots correspond to the neighboring animal silhouette in order of size. Animal silhouettes are public domain from phylopic.org under Creative Commons licenses. Box and whisker plots denote the median values (line), 25th to 75th percentiles, and mean (+). The whiskers extend to the maximum and minimum values. An unpaired t-test was performed, and **** denotes P < 0.0001.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Andersen LW, Lydersen C, Frie AK, Rosing-Asvid A, Hauksson E, Kovacs KM. A population on the edge: genetic diversity and population structure of the world's northernmost harbour seals (Phoca vitulina). Biol J Linn Soc. 2011:102(2):420–439. 10.1111/j.1095-8312.2010.01577.x. - DOI
    1. Berta A, Churchill M, Boessenecker RW. The origin and evolutionary biology of pinnipeds: seals, sea lions and walruses. Annu Rev Earth Planet Sci. 2018:46(1):203–228. 10.1146/annurev-earth-082517-010009. - DOI
    1. Blanchet M-A, Vincent C, Womble JN, Steingass SM, Desportes G. Harbour seals: population structure, status and threats in a rapidly changing environment. Oceans 2021:2(1):41–63. 10.3390/oceans2010003. - DOI
    1. Buchfink B, Reuter K, Drost HG. Sensitive protein alignments at tree-of-life scale using DIAMOND. Nat Methods. 2021:18(4):366–368. 10.1038/s41592-021-01101-x. - DOI - PMC - PubMed
    1. Cottrell PE, Jeffries S, Beck B, Ross PS. Growth and development in free-ranging harbor seal (Phoca vitulina) pups from southern British Columbia, Canada. Mar Mammal Sci. 2002:18(3):721–733. 10.1111/j.1748-7692.2002.tb01069.x. - DOI

Publication types

Substances

LinkOut - more resources

-