A genomics approach reveals insights into the importance of gene losses for mammalian adaptations

Case studies investigating the fate of selected genes have uncovered associations between gene losses and several mammalian phenotypes.

“Case studies investigating the fate of selected genes uncovered associations between gene losses and several mammalian phenotypes14–16.”

• cites [14] Brawand, D., Wahli, W. & Kaessmann, H. Loss of egg yolk genes in mammals and the origin of lactation and placentation. PLoS Biol. 6, e63 (2008). sourceSupported
• cites [15] Meredith, R. W., Zhang, G., Gilbert, M. T., Jarvis, E. D. & Springer, M. S. Evidence for a single loss of mineralized teeth in the common avian ancestor. Science 346, 1254390 (2014). sourceNot checked — no full text of the source
• cites [16] Fang, X. et al. Genome-wide adaptive complexes to underground stresses in blind mole rats Spalax. Nat. Commun. 5, 3966 (2014). sourceSupported

We validated stop codon mutations, splice site mutations, and frameshifting insertions/deletions with unassembled sequencing reads stored in the sequence read archive (SRA) or the NCBI trace archive.

“we validated stop codon mutations, splice site mutations, and frameshifting insertions/deletions with unassembled sequencing reads stored in the sequence read archive (SRA)65 or the NCBI trace archive.”

• cites [65] Kodama, Y., Shumway, M. & Leinonen, R. International Nucleotide Sequence Database Collaboration. The sequence read archive: explosive growth of sequencing data. Nucleic Acids Res. 40, D54–D56 (2012). sourceSupported

The ability of fruit bats to excrete excess dietary water while preserving electrolytes is likely facilitated by the loss of SLC22A12 (URAT1), SLC2A9 (GLUT9), and SLC22A6 (OAT1), three renal transporter genes whose knockout in mice reduces urine osmolality.

“Our results indicate that this ability is likely facilitated by the loss of SLC22A12 (URAT1), SLC2A9 (GLUT9), and SLC22A6 (OAT1), three renal transporter genes whose knockout in mice reduces urine osmolality31,32 (Fig. 4 and Supplementary Note 4).”

• cites [31] Eraly, S. A. et al. Multiple organic anion transporters contribute to net renal excretion of uric acid. Physiol. Genom. 33, 180–192 (2008). sourceNot checked — no full text of the source
• cites [32] Preitner, F. et al. Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy. Proc. Natl Acad. Sci. USA 106, 15501–15506 (2009). sourcePartly supported

  Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured

• AssumptionRests on an assumption: A gene loss that predates or coincides with the evolution of an adaptive phenotype and whose knockout phenotype resembles that phenotype likely contributed to the adaptation.

The loss of FAM3B may contribute to enhanced hepatic insulin sensitivity, as observed in FAM3B knockout mice.

“The loss of FAM3B, encoding a cytokine that is co-secreted with insulin from pancreatic beta-cells39, may contribute to enhanced hepatic insulin sensitivity, as observed in FAM3B knockout mice40.”

• cites [39] Yang, J. et al. Mechanisms of glucose-induced secretion of pancreatic-derived factor (PANDER or FAM3B) in pancreatic beta-cells. Diabetes 54, 3217–3228 (2005). sourceNot checked — no full text of the source
• cites [40] Moak, S. L. et al. Enhanced glucose tolerance in pancreatic-derived factor (PANDER) knockout C57BL/6 mice. Dis. Models Mech. 7, 1307–1315 (2014). sourceSupported

The "less is more" principle likely applies to the loss of genes involved in insulin signaling (FAM3B and FFAR3) and renal function (SLC22A12, SLC22A6, SLC2A9, and RHBG) in fruit bats.

“This “less is more” principle56 likely applies to the loss of genes involved in insulin signaling (FAM3B and FFAR3) and renal function (SLC22A12, SLC22A6, SLC2A9, and RHBG) in fruit bats”

• cites [56] Olson, M. V. When less is more: gene loss as an engine of evolutionary change. Am. J. Hum. Genet. 64, 18–23 (1999). sourceSupported

Placental mammals are separated by an evolutionary distance of ~0.5 or fewer substitutions per neutral site.

“Since placental mammals are separated by an evolutionary distance of ~0.5 or fewer substitutions per neutral site61”

• cites [61] Hiller, M. et al. Computational methods to detect conserved non-genic elements in phylogenetically isolated genomes: application to zebrafish. Nucleic Acids Res. 41, e151 (2013). sourcePartly supported

  The Introduction’s Figure 1 caption identifies human and mouse as a comparatively close pair and describes evolutionary distances in neutral substitutions per site. The Discussion likewise uses the human–mouse distance as a benchmark, but the available text gives neither a value of ~0.5 nor an upper bound for placental mammals generally. (LLM, conf=0.78)

  Experimental — accuracy not yet measured

The loss of FFAR3 may explain why fruit bats secrete substantially more insulin than other mammals.

“The loss of FFAR3, encoding an insulin secretion inhibitor37, may explain why fruit bats secrete substantially more insulin than other mammals38.”

• cites [37] Priyadarshini, M. & Layden, B. T. FFAR3 modulates insulin secretion and global gene expression in mouse islets. Islets 7, e1045182 (2015). sourceSupported
• cites [38] Protzek, A. O. et al. Insulin and glucose sensitivity, insulin secretion and beta-cell distribution in endocrine pancreas of the fruit bat Artibeus lituratus. Comparative biochemistry and physiology. Comp. Biochem. Physiol. A Mol. Integr. Physiol. 157, 142–148 (2010). sourceSupported

Gene loss in humans or human individuals can be adaptive by enhancing protection against pathogenic bacteria or diseases such as plasmodium and HIV infections, and sepsis.

“These studies also revealed that gene loss in humans or human individuals can be adaptive by enhancing protection against pathogenic bacteria or diseases such as plasmodium and HIV infections, and sepsis17–20.”

• cites [17] Liu, R. et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86, 367–377 (1996). sourcePartly supported

  The Abstract and Discussion report that a CKR-5 deletion appears to protect two multiply exposed individuals from HIV-1 infection. The Discussion also describes a loss-of-expression DARC allele that provides resistance to Plasmodium vivax, but treats a selective advantage for the CKR-5 deletion as possible rather than established. The paper does not address protection against pathogenic bacteria or sepsis. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites [18] Singh, S. K., Hora, R., Belrhali, H., Chitnis, C. E. & Sharma, A. Structural basis for Duffy recognition by the malaria parasite Duffy-binding-like domain. Nature 439, 741–744 (2006). sourceNot checked — no full text of the source
• cites [19] Wang, X., Grus, W. E. & Zhang, J. Gene losses during human origins. PLoS Biol. 4, e52 (2006). sourceSupported
• cites [20] Wang, X. et al. Specific inactivation of two immunomodulatory SIGLEC genes during human evolution. Proc. Natl Acad. Sci. USA 109, 9935–9940 (2012). sourcePartly supported

  The paper reports that SIGLEC13 and SIGLEC17 became nonfunctional and proposes that bacterial pathogens may have selected for their loss (p. 1; Timing of SIGLEC Pseudogenization Events During Hominin Evolution, p. 4). It does not establish that the losses enhanced protection, and the cited passages do not support the claim’s specific examples of Plasmodium, HIV, or sepsis. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

The study detected the convergent loss of ACP4, a gene associated with the enamel disorder amelogenesis imperfecta.

“As a novel result, we detected the convergent loss of ACP4 (Fig. 5b and Supplementary Fig. 33), a gene that is associated with the enamel disorder amelogenesis imperfecta46.”

• cites [46] Seymen, F. et al. Recessive mutations in ACPT, encoding testicular acid phosphatase, cause hypoplastic amelogenesis imperfecta. Am. J. Hum. Genet. 99, 1199–1205 (2016). sourceCould not verify

  The supplied passage and searches for ACP4 and ACPT returned only a list of URLs, with no substantive passage or section/page information. Our accessible copy therefore does not establish whether ACP4 is associated with amelogenesis imperfecta. The convergent-loss finding is presented as the citing authors’ own result, not as a finding attributed to this source. (LLM, conf=0.70)

  Experimental — accuracy not yet measured

The loss of FATP6 (SLC27A6) indicates that sugars replace fatty acids as the major energy source in the heart of fruit bats.

“For example, the loss of FATP6 (SLC27A6) that transports fatty acids into cardiac myocytes41 indicates that sugars replace fatty acids as the major energy source in the heart.”

• cites [41] Gimeno, R. E. et al. Characterization of a heart-specific fatty acid transport protein. J. Biol. Chem. 278, 16039–16044 (2003). sourceSupported

Searching for gene losses shared between the fully aquatic cetacean and manatee lineages revealed KLK8, a gene loss that correlates with skin and neuroanatomical differences of aquatic mammals.

“Searching for gene losses shared between the fully aquatic cetacean and manatee lineages revealed KLK8, a gene loss that correlates with skin and neuroanatomical differences of aquatic mammals50.”

• cites [50] Hecker, N., Sharma, V. & Hiller, M. Transition to an aquatic habitat permitted the repeated loss of the pleiotropic KLK8 gene in mammals. Genome Biol. Evol. 9, 3179–3188 (2017). sourceSupported

The loss of RHBG may contribute to the ability of fruit bats to efficiently excrete excess potassium and efficiently reabsorb scarce sodium.

“Since ammonium inhibits potassium secretion and sodium reabsorption33, the loss of the ammonium secreting RHBG may contribute to the ability of fruit bats to efficiently excrete excess potassium and efficiently reabsorb scarce sodium34.”

• cites [33] Weiner, I. D. Roles of renal ammonia metabolism other than in acid-base homeostasis. Pediatr. Nephrol. 32, 933–942 (2017). sourcePartly supported

  The section “Intrarenal roles of ammonia other than acid-base homeostasis” (page not provided) reports that ammonia inhibits collecting-duct potassium secretion and sodium reabsorption, supporting the proposed physiological mechanism. It does not address RHBG loss in fruit bats or show that such loss improves their potassium excretion or sodium reabsorption. (LLM, conf=0.85)

  Experimental — accuracy not yet measured
• cites [34] Studier, E. H. & Wilson, D. E. Natural urine concentrations and composition in neotropical bats. Comp. Biochem. Physiol. A Physiol. 75, 509–515 (1983). sourceNot checked — no full text of the source

• AssumptionRests on an assumption: A gene loss that predates or coincides with the evolution of an adaptive phenotype and whose knockout phenotype resembles that phenotype likely contributed to the adaptation.

MMP12 encodes a potent protease that degrades elastin, the major component of elastic fibers.

“MMP12 encodes a potent protease that degrades elastin, the major component of elastic fibers54.”

• cites [54] Shipley, J. M., Wesselschmidt, R. L., Kobayashi, D. K., Ley, T. J. & Shapiro, S. D. Metalloelastase is required for macrophage-mediated proteolysis and matrix invasion in mice. Proc. Natl Acad. Sci. USA 93, 3942–3946 (1996). sourceSupported

A total of 85-91% of the genes remaining after step 7 had inactivating mutations only in a single exon that is not entirely conserved.

“A total of 85–91% of the genes remaining after step 7 had inactivating mutations only in a single exon that is not entirely conserved (Supplementary Figs. 10 and 11).”

The analysis revealed genes with hair- and epidermis-related functions that are specifically lost in all four cetaceans present in the analysis (dolphin, orca, sperm whale, minke whale).

“Our analysis revealed genes with hair- and epidermis-related functions that are specifically lost in all four cetaceans present in our analysis (dolphin, orca, sperm whale, minke whale) (Fig. 2; all genes, their inactivating mutations and loss date estimations are described in detail in Supplementary Note 1, Supplementary Figs. 14–17, and Supplementary Table 5).”

By requiring that inactivating mutations occur in multiple exons and that less than 60% of the reading frame remains intact, the approach misclassifies ≤0.3% of 13,486 conserved genes as lost.

“By requiring that inactivating mutations occur in multiple exons and that less than 60% of the reading frame remains intact, our approach misclassifies ≤0.3% of 13,486 conserved genes as lost”

The study identified previously known losses of the tooth-specific genes MMP20 and C4orf26 that are essential for enamel formation in four mammals that independently lost tooth enamel.

“As a proof of concept, we searched for genes that are lost in four mammals that independently lost tooth enamel (Fig. 5a) and identified previously known losses of the tooth-specific genes MMP20 and C4orf2615 that are essential for enamel formation (Fig. 5b, Supplementary Note 6, and Supplementary Table 6).”

• cites [15] Meredith, R. W., Zhang, G., Gilbert, M. T., Jarvis, E. D. & Springer, M. S. Evidence for a single loss of mineralized teeth in the common avian ancestor. Science 346, 1254390 (2014). sourceNot checked — no full text of the source

Cetaceans lost the peeling skin syndrome gene TGM5 that cross-links structural corneocyte proteins.

“cetaceans also lost the peeling skin syndrome gene TGM5 that cross-links structural corneocyte proteins.”

Both scaly mammals (armadillo and pangolin) are the only species in the data set that have lost the DDB2 gene.

“Surprisingly, we found that both scaly mammals are the only species in our data set that have lost the DDB2 gene (Fig. 5, Supplementary Note 7, Supplementary Fig. 34, and Supplementary Table 7).”

The series of filters reduced the number of conserved genes with inactivating mutations such that gene loss is incorrectly inferred for ≤0.33% (32-45) of 13,486 genes.

“The series of filters integrated in our approach drastically reduced the number of conserved genes with inactivating mutations such that gene loss is incorrectly inferred for ≤0.33% (32–45) of these 13,486 genes (Fig. 1b and Supplementary Table 1).”

The sperm whale is the only mammal in the data set that has lost the BCO1 gene.

“This likely explains why the sperm whale is the only mammal in our data set that has lost the BCO1 gene, which encodes an enzyme that cleaves beta-carotene into retinal (a form of vitamin A) (Fig. 3, Supplementary Note 3, and Supplementary Fig. 20).”

Inactivation (loss) of ancestral protein-coding genes is one genetic mechanism contributing to phenotypic differences.

“One genetic mechanism contributing to phenotypic differences is the inactivation (loss) of ancestral protein-coding genes10,11.”

• cites [10] Stedman, H. H. et al. Myosin gene mutation correlates with anatomical changes in the human lineage. Nature 428, 415–418 (2004). sourceNot checked — no full text of the source
• cites [11] Albalat, R. & Canestro, C. Evolution by gene loss. Nat. Rev. Genet. 17, 379–391 (2016). sourceNot checked — no full text of the source

The approach was tested on 13,486 human genes conserved in mouse, rat, cow, and dog, which should not exhibit real inactivating mutations.

“We tested our approach on a large set of 13,486 human genes that are conserved in mouse, rat, cow, and dog, and thus should not exhibit real inactivating mutations.”

The loss of BCO1 is probably a consequence of relaxed selection after the sperm whale's dietary specialization evolved.

“Since the loss of BCO1 is unlikely to be causally involved in the evolution of a diet rich in squid, its loss is probably a consequence of relaxed selection after this dietary specialization evolved in the sperm whale.”

• AssumptionRests on an assumption: The timing of gene loss relative to the evolution of an adaptive phenotype can distinguish whether the loss contributed to or was a consequence of the adaptation.

Mice in which GSDMA, DSG4, or DSC1 are knocked out exhibit key aspects of the cetacean skin morphology, in particular a thicker epidermis and loss of hair.

“Mice in which GSDMA, DSG4, or DSC1 are knocked out exhibit key aspects of the cetacean skin morphology, in particular a thicker epidermis and loss of hair.”

Gene losses as a consequence of adaptation can reveal unknown aspects related to the adaptation.

“Importantly, gene losses as a consequence of adaptation can reveal unknown aspects related to the adaptation.”

The loss of AMPD3 likely improves O2 transport in sperm whales.

“the loss of AMPD3 that likely improves O2 transport in sperm whales”

The loss of FFAR3 and FAM3B is likely adaptive by improving metabolic processing of ingested sugar.

“We identified the loss of two genes involved in insulin metabolism and signaling (FFAR3 and FAM3B) that is likely adaptive by improving metabolic processing of ingested sugar (Fig. 4 and Supplementary Note 5).”

• AssumptionRests on an assumption: A gene loss that predates or coincides with the evolution of an adaptive phenotype and whose knockout phenotype resembles that phenotype likely contributed to the adaptation.

Genome alignments are more appropriate for detecting gene loss events than existing gene annotations, since the absence of an annotation for a gene can also be due to incomplete genomic data or other artifacts.

“Genome alignments are more appropriate for detecting gene loss events than existing gene annotations, since the absence of an annotation for a gene can also be due to incomplete genomic data or other artifacts.”

Fruit bats (large and black flying fox) feed predominantly on large amounts of juice extracted from fruits.

“These fruit bats feed predominantly on large amounts of juice extracted from fruits.”

Explosive air exchange is facilitated by extensive elastic tissue in the lungs that permits a greater expansion during inhalation and whose elastic recoil helps to empty the lungs quickly.

“Explosive air exchange is facilitated by extensive elastic tissue in the lungs that permits a greater expansion during inhalation and whose elastic recoil helps to empty the lungs quickly53.”

• cites [53] Piscitelli, M. A., Raverty, S. A., Lillie, M. A. & Shadwick, R. E. A review of cetacean lung morphology and mechanics. J. Morphol. 274, 1425–1440 (2013). sourceNot checked — no full text of the source

The loss of the cardiac fatty acid transporter SLC27A6 suggests that the heart of fruit bats is highly dependent on sugar as the main energy source.

“For example, the loss of the cardiac fatty acid transporter SLC27A6 suggests that the heart of fruit bats is highly dependent on sugar as the main energy source.”

This irreversibility may indicate that gene function diversity is preferentially preserved in generalist species.

“This irreversibility may indicate that gene function diversity is preferentially preserved in generalist species”

The convergent loss of DDB2 in mammals whose sun-exposed, dorsal skin is covered by scales suggests the possibility that scales are sufficient to protect from UV light-induced DNA damage.

“Thus, the convergent loss of DDB2 in mammals whose sun-exposed, dorsal skin is covered by scales suggests the possibility that scales are sufficient to protect from UV light-induced DNA damage.”

Loss of genes with specific functions and restricted expression patterns can contribute to morphological adaptations.

“the loss of epidermis-related genes (DSG4, DSC1, TGM5, and GSDMA) in cetaceans suggests that the loss of genes with specific functions and restricted expression patterns can also contribute to morphological adaptations”

Mutations in an individual exon of an otherwise-conserved gene are not sufficient to infer gene loss.

“This shows that mutations in an individual exon of an otherwise-conserved gene is not sufficient to infer gene loss.”

Cetaceans have no hair to reduce drag while swimming.

“no hair to reduce drag while swimming27”

• cites [27] Spearman, R. I. The epidermal stratum corneum of the whale. J. Anat. 113, 373–381 (1972).Not checked — no full text of the source

Gene loss can be beneficial by providing an evolutionary mechanism for phenotypic adaptations.

“gene loss can be beneficial by providing an evolutionary mechanism for phenotypic adaptations11”

• cites [11] Albalat, R. & Canestro, C. Evolution by gene loss. Nat. Rev. Genet. 17, 379–391 (2016). sourceNot checked — no full text of the source

The loss of MMP12 may contribute to explosive exhalation in aquatic mammals.

“the loss MMP12 that may contribute to explosive exhalation in aquatic mammals”

The loss of MOGAT2 and FABP6 is likely a consequence of the fat-poor frugivorous diet.

“The loss of MOGAT2 and FABP6, two genes involved in intestinal fat digestion, is likely also a consequence of the fat-poor frugivorous diet.”

• AssumptionRests on an assumption: The timing of gene loss relative to the evolution of an adaptive phenotype can distinguish whether the loss contributed to or was a consequence of the adaptation.

The loss of ancestral genes may be a driver for a variety of adaptations in mammals.

“but may also be a driver for a variety of adaptations in mammals”

The simplification of the renal transporter repertoire is an evolutionary mechanism that contributes to the ability of fruit bats to excrete excess dietary water while preserving electrolytes.

“Together, these gene losses suggest that the simplification of the renal transporter repertoire is an evolutionary mechanism that contributes to the ability of fruit bats to excrete excess dietary water while preserving electrolytes.”

A genome-wide search can identify known and novel gene losses that are involved in the independent loss of enamel.

“This shows that a genome-wide search can identify known and novel gene losses that are involved in the independent loss of enamel.”

Gene loss could influence macroevolutionary trajectories by hampering phenotypic reversal in highly adapted specialists.

“gene loss could influence macroevolutionary trajectories by hampering phenotypic reversal in highly adapted specialists”

The loss of AMPD3 could be a novel adaptive mechanism to improve O2 transport from blood to tissue in a long-diving mammal.

“Thus, the loss of AMPD3 could be a novel adaptive mechanism to improve O2 transport from blood to tissue in a long-diving mammal.”

Cetaceans have a much thicker epidermis that enhances physical barrier properties and protects against the greater pressure in their much denser environment.

“a much thicker epidermis that enhances physical barrier properties and protects against the greater pressure in their much denser environment25”

• cites [25] Reeb, D., Best, P. B. & Kidson, S. H. Structure of the integument of southern right whales. Eubalaena Aust. Anat. Rec. 290, 596–613 (2007). sourceNot checked — no full text of the source

Fruit bats' specialized diet consists predominantly of sugars and very little fat and protein.

“The second challenge faced by fruit bats is the nutritional composition of their specialized diet, consisting predominantly of sugars and very little fat and protein36.”

• cites [36] Voigt, C. C., Zubaid, A., Kunz, T. H. & Kingston, T. Sources of assimilated proteins in old and new world phytophagous bats. Biotropica 43, 108–113 (2010). sourceNot checked — no full text of the source

The loss of these three genes suggests that fewer desmosomes and impaired protein cross-links could be a mechanistic explanation for the high shedding rate of stratum corneum cells.

“The loss of these three genes suggests that fewer desmosomes and impaired protein cross-links could be a mechanistic explanation for the high shedding rate of stratum corneum cells.”

Gene loss is a mechanism that has likely contributed to adaptive evolution in several mammals.

“Our results suggest that gene loss is a mechanism that has likely contributed to adaptive evolution in several mammals.”

The loss of AMPD3 is probably adaptive for long-diving sperm whales as a lower affinity facilitates O2 release from hemoglobin to the O2-depleted tissue.

“This is probably adaptive for long-diving sperm whales as a lower affinity facilitates O2 release from hemoglobin to the O2-depleted tissue (Fig. 3 and Supplementary Note 2).”

• AssumptionRests on an assumption: A gene loss that predates or coincides with the evolution of an adaptive phenotype and whose knockout phenotype resembles that phenotype likely contributed to the adaptation.

The loss of ancestral genes is a predictable consequence of phenotypic evolution.

“the loss of ancestral genes is not only a predictable consequence of phenotypic evolution”

Gene loss as a consequence of adaptation is likely the result of relaxed selection to maintain a gene whose function became obsolete.

“Gene loss as a consequence of adaptation is likely the result of relaxed selection to maintain a gene whose function became obsolete.”

The specific loss of the elastin degrading MMP12 suggests a mechanism that could contribute to the extensive elastic lung tissue necessary for explosive exhalation.

“Thus, the specific loss of the elastin degrading MMP12 suggests a mechanism that could contribute to the extensive elastic lung tissue necessary for explosive exhalation.”

• AssumptionRests on an assumption: A gene loss that predates or coincides with the evolution of an adaptive phenotype and whose knockout phenotype resembles that phenotype likely contributed to the adaptation.

For all previously unknown gene losses presented, the loss was further confirmed by validating the gene-inactivating mutations with unassembled sequencing reads from the respective species.

“For all previously unknown gene losses presented here, we further confirmed the loss by validating the gene-inactivating mutations with unassembled sequencing reads from the respective species.”

Armadillo and pangolin independently evolved body armor in the form of scales.

“Next, we searched for gene losses specific to armadillo and pangolin, two mammals that independently evolved body armor in the form of scales.”

By discovering novel associations between convergent gene losses and independently evolved phenotypic adaptations, the study provides additional evidence that gene losses are not only a consequence, but can be a repeated mechanism for similar phenotypic adaptations.

“Overall, by discovering novel associations between convergent gene losses and independently evolved phenotypic adaptations, we provide additional evidence that gene losses are not only a consequence, but can be a repeated mechanism for similar phenotypic adaptations.”

Gene loss is likely irreversible after several inactivating mutations accumulated.

“gene loss is likely irreversible after several inactivating mutations accumulated”

DSG4 and DSC1 encode components of desmosomes that mediate cell adhesion in the upper epidermis.

“DSG4 and DSC1 encode components of desmosomes that mediate cell adhesion in the upper epidermis”

The loss of AQP6 indicates that additional gene losses could be related to kidney adaptations in fruit bats.

“Finally, the loss of poorly characterized kidney genes such as AQP6, the only aquaporin family member that functions as an anion-channel instead of a water channel35, indicates that additional gene losses could be related to kidney adaptations in fruit bats.”

• cites [35] Liu, K. et al. Conversion of aquaporin 6 from an anion channel to a water-selective channel by a single amino acid substitution. Proc. Natl Acad. Sci. USA 102, 2192–2197 (2005). sourceNot checked — no full text of the source

The loss of DDB2 in scaly mammals suggests the possibility that their body armor sufficiently protects the animal against UV light-induced DNA damage.

“Likewise, the loss of DDB2 in scaly mammals suggests the possibility that their body armor sufficiently protects the animal against UV light-induced DNA damage.”

Cetaceans have a high shedding rate of cells in the stratum corneum that maintains a smooth surface and limits microbe colonization.

“a high shedding rate of cells in the stratum corneum that maintains a smooth surface and limits microbe colonization26”

• cites [26] Hicks, B. D., St. Aubin, D. J., Geraci, J. R. & Brown, W. R. Epidermal growth in the bottlenose dolphin Tursiops truncatus. J. Invest. Dermatol. 85, 60–63 (1985). sourceNot checked — no full text of the source