Proteases participate in multiple biological processes (both physiological and pathological), hence playing important roles in mammalian evolution 1 . Given their diverse functions, the analysis of the genomic variants of proteases in different species can yield a wealth of information on diverse molecular paths 2 . They are key in organism homoeostasis maintenance, and for that reason they require a tight regulatory system, which makes them an important evolutionary target among mammals 3;4 . Failures in this system may develop in pathologies 5;6 .
Sperm whale (Physeter macrocephalus, is an aquatic mammal from the Cetacean suborder, (part of the Artiodactyla order, or even-toes ungulates). Sperm whales are part of the Odontoceti infraorder (toothed whales), and present some features of interest such as its great size, an apparently enhanced cancer resistance (in line with Peto’s paradox) 7 and an advance cognitive system 8–11 . Additionally, several aquatic adaptations allow these animals to survive in their environment. This adaptations may include skin modification, an altered blood pressure and coagulation systems, and immunology mutations (which may relate to longevity and other processes) 12 .
Through the analysis of the sperm whales’ genome, we expected to unravel some of this adaptations, in hope that one day this findings could be used to advance in human ageing research.
Genome preparation was performed in the McDonnell Genome Institute (Washington University), through Illumina Sequence from a skin shed sample (adult female) 14 .
Degradome annotation was performed with the BATI pipeline (figure 2). Alignments were performed using in-house software, based on Clustal-o and rendered with postscript. Orthologs from other species were obtained from available databases or annotated with the BATI pipeline from the genomic sequences. These alignments were performed using in-house software (based on Clustal-o) and postscript.
MMP12 (inflammation process 15 ), TPSAB1 (mast cells de-granulation 16 ), and MASP2 (complement system 17 ), present premature stop codons, expected to truncate the function of their proteins. Ingeneralthesealterationsseemtopointtowardsamorelaxinflammatoryresponsewhich has been linked to longevity.
MMP7, a matrix metalloprotease 18 , seems to be truncated. Since the second member of this family (MMP26) is primate-specific, this protease family, which has been involved in metastasis, is absent in bowhead whale. CASP13 is duplicated in sperm whale and participates in the apoptotic process 19 . These alterations might contribute to the particular solution to Peto’s paradox 7;20 in this species.
CAPN12, related to the hair follicle 21 , is missing in all cetaceans. KLK7 and KLK8 (cutaneous homoeostasis, and stratum corneum maintenance 22;23 ) are truncated in a similar way. Overall this changes may explain cetacean skin adaptations to underwater life and the specific changes undergone by sperm whale 24 .
F12, KLKB1, and AMZ2, that might be involved in the regulation blood pressure and coagulation 25;25;26 , aretruncated. TMPRSS11F andTMPRSS11B,relatedtothecoagulationsystem 13 , are also truncated. Altogether this results shows a differently regulated blood homoeostasis system, which should allow the sperm whale to live underwater and dive to great depths.
Peptidases CPA2, CPA3 and CPO are all truncated (both CPA2 and CPO conservedly among cetaceans). And, as expected, contrary to toothless whales, KLK4 and MMP20, dentition-related proteases are present and apparently functional 12;13 . All this alterations may be key to the sperm whale adaptation to the sea, many of them asserted by the fact that the mutation is shared identical or functionally in other whales.