# Transcriptomic Responses of the Heart and Brain to Anoxia in the Western Painted Turtle

**Authors:** Sarah W. Keenan, Craig A. Hill, Cyriac Kandoth, Leslie T. Buck, Daniel E. Warren

PMC · DOI: 10.1371/journal.pone.0131669 · PLoS ONE · 2015-07-06

## TL;DR

This study explores how the heart and brain of western painted turtles respond at the gene level to anoxia, revealing patterns that help them survive without oxygen for long periods.

## Contribution

The paper provides new insights into the transcriptomic mechanisms enabling anoxia tolerance in turtles, focusing on gene expression patterns in the heart and brain.

## Key findings

- The ventricle showed a significant decrease in total RNA content compared to the telencephalon under anoxia.
- Most genes affected by anoxia were immediate early genes and transcription factors, suggesting a role in metabolic and transcriptional arrest.
- Gene expression changes in the telencephalon correlated with predicted metabolic costs, favoring shorter genes with fewer exons.

## Abstract

Painted turtles are the most anoxia-tolerant tetrapods known, capable of surviving without oxygen for more than four months at 3°C and 30 hours at 20°C. To investigate the transcriptomic basis of this ability, we used RNA-seq to quantify mRNA expression in the painted turtle ventricle and telencephalon after 24 hours of anoxia at 19°C. Reads were obtained from 22,174 different genes, 13,236 of which were compared statistically between treatments for each tissue. Total tissue RNA contents decreased by 16% in telencephalon and 53% in ventricle. The telencephalon and ventricle showed ≥ 2x expression (increased expression) in 19 and 23 genes, respectively, while only four genes in ventricle showed ≤ 0.5x changes (decreased expression). When treatment effects were compared between anoxic and normoxic conditions in the two tissue types, 31 genes were increased (≥ 2x change) and 2 were decreased (≤ 0.5x change). Most of the effected genes were immediate early genes and transcription factors that regulate cellular growth and development; changes that would seem to promote transcriptional, translational, and metabolic arrest. No genes related to ion channels, synaptic transmission, cardiac contractility or excitation-contraction coupling changed. The generalized expression pattern in telencephalon and across tissues, but not in ventricle, correlated with the predicted metabolic cost of transcription, with the shortest genes and those with the fewest exons showing the largest increases in expression.

## Full-text entities

- **Genes:** ddit4.S (DNA damage inducible transcript 4 S homeolog) [NCBI Gene 379481] {aka ddit4, enpr02, redd1}, Timm23 (translocase of inner mitochondrial membrane 23) [NCBI Gene 53600] {aka Tim23}, PPIL3 [NCBI Gene 101948174], Epo (erythropoietin) [NCBI Gene 13856], tert.L (telomerase reverse transcriptase L homeolog) [NCBI Gene 373635] {aka est2, tcs1, telomerase, tert, tert-A, tp2}, Apold1 [NCBI Gene 101933471], jun.L (jun proto-oncogene L homeolog) [NCBI Gene 399400] {aka AP-1, c-Jun, jun}, Tiparp (TCDD-inducible poly(ADP-ribose) polymerase) [NCBI Gene 99929] {aka ARTD14, PARP7}, fos.S (FBJ murine osteosarcoma viral oncogene homolog S homeolog) [NCBI Gene 447201] {aka c-fos, fos, xfos}, bcl2.S (B-cell CLL/lymphoma 2 S homeolog) [NCBI Gene 100271914] {aka bcl-2, bcl2, xBcl-2, xbcl2}, Klf10 (Kruppel-like transcription factor 10) [NCBI Gene 21847] {aka EGR[a], Egral, Gdnfif, TIEG-1, Tieg, Tieg1}, junb.L (jun B proto-oncogene L homeolog) [NCBI Gene 432129] {aka junb}, Clk4 [NCBI Gene 101938022], ets2.L (v-ets avian erythroblastosis virus E26 oncogene homolog 2 L homeolog) [NCBI Gene 397877] {aka ets-2, ets-2b, ets2-a, ets2-b}, KCNH2 (potassium voltage-gated channel subfamily H member 2) [NCBI Gene 3757] {aka ERG-1, ERG1, H-ERG, HERG, HERG1, Kv11.1}, ccn1.S (cellular communication network factor 1 S homeolog) [NCBI Gene 379598] {aka Xcyr61, cyr61, cyr61.S}, Activating transcription factor 3 [NCBI Gene 101939025], CYR61 [NCBI Gene 101942375], FOS (Fos proto-oncogene, AP-1 transcription factor subunit) [NCBI Gene 2353] {aka AP-1, C-FOS, p55}, HES4 (hes family bHLH transcription factor 4) [NCBI Gene 57801] {aka bHLHb42}, Mapk1 (mitogen-activated protein kinase 1) [NCBI Gene 26413] {aka 9030612K14Rik, ERK, Erk2, MAPK2, PRKM2, Prkm1}, Clk3 [NCBI Gene 101944787], nr4a1.L (nuclear receptor subfamily 4 group A member 1 L homeolog) [NCBI Gene 373674] {aka NGFI-B, gfrp1, hmr, n10, nak-1, ngf1b}, Bhlhe40 (basic helix-loop-helix family, member e40) [NCBI Gene 20893] {aka Bhlhb2, C130042M06Rik, CR8, Clast5, Dec1, Sharp2}, btg1.S (B-cell translocation gene 1, anti-proliferative S homeolog) [NCBI Gene 380519] {aka btg1, xbtg1}, Mknk1 (MAP kinase-interacting serine/threonine kinase 1) [NCBI Gene 17346] {aka 2410048M24Rik, Mnk1}, Sik1 (salt inducible kinase 1) [NCBI Gene 17691] {aka Hrt-20, Msk, Sik, Sik-1, Snf1lk}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, dusp1.L (dual specificity phosphatase 1 L homeolog) [NCBI Gene 380262] {aka XCL100, dusp1, dusp1-a}, CCN1 (cellular communication network factor 1) [NCBI Gene 3491] {aka CYR61, GIG1, IBP-10, IGFBP-10, IGFBP10}, Klf2 [NCBI Gene 101931892], Cdo1 (cysteine dioxygenase 1, cytosolic) [NCBI Gene 12583] {aka 1300002L19Rik, Cdo, D18Ucla3}, Nfil3 (nuclear factor, interleukin 3, regulated) [NCBI Gene 18030] {aka E4BP4}, Cish (cytokine inducible SH2-containing protein) [NCBI Gene 12700] {aka CIS-1, CIS1, Cis, F17, F23, SOCS}, klf2.S (KLF transcription factor 2 S homeolog) [NCBI Gene 380122] {aka Xklf2, klf2, lklf}, Srsf5 (serine and arginine-rich splicing factor 5) [NCBI Gene 20384] {aka Sfrs5}, Csrnp1 (cysteine-serine-rich nuclear protein 1) [NCBI Gene 215418] {aka 4931429D10Rik, Axud1, CSRNP-1, URAX1, taip-3}, Depp1 (DEPP1 autophagy regulator) [NCBI Gene 213393] {aka 8430408G22Rik, Depp, Fseg}, Ccnj (cyclin J) [NCBI Gene 240665] {aka D430039C20Rik}, APOLD1 (apolipoprotein L domain containing 1) [NCBI Gene 81575] {aka BDVAS, VERGE}, Clk1 [NCBI Gene 101947555], Il8 [NCBI Gene 101952445]
- **Diseases:** arrest (MESH:D006323), heart ischemia (MESH:D007511), Anoxia (MESH:D000860), lactic acidosis (MESH:D000140), Ventricle (MESH:D002551), anoxic (MESH:D002534), respiratory and metabolic acidosis (MESH:D000142), cancerous (MESH:D009369), metabolic depression (MESH:D008659), inflammation (MESH:D007249)
- **Species:** Emydidae (pond turtles, family) [taxon 8476], Trachemys scripta (pond slider, species) [taxon 34903], Taeniopygia guttata (zebra finch, species) [taxon 59729], Xenopus laevis (African clawed frog, species) [taxon 8355], Chrysemys picta bellii (western painted turtle, subspecies) [taxon 8478], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Chrysemys picta (Painted turtle, species) [taxon 8479]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC4493013/full.md

## References

72 references — full list in the complete paper: https://tomesphere.com/paper/PMC4493013/full.md

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Source: https://tomesphere.com/paper/PMC4493013