Elephant Genomes Reveal Accelerated Evolution in Mechanisms Underlying Disease Defenses

Abstract

Disease susceptibility and resistance are important factors for the conservation of endangered species, including elephants. We analyzed pathology data from 26 zoos and report that Asian elephants have increased neoplasia and malignancy prevalence compared with African bush elephants. This is consistent with observed higher susceptibility to tuberculosis and elephant endotheliotropic herpesvirus (EEHV) in Asian elephants. To investigate genetic mechanisms underlying disease resistance, including differential responses between species, among other elephant traits, we sequenced multiple elephant genomes. We report a draft assembly for an Asian elephant, and defined 862 and 1,017 conserved potential regulatory elements in Asian and African bush elephants, respectively. In the genomes of both elephant species, conserved elements were significantly enriched with genes differentially expressed between the species. In Asian elephants, these putative regulatory regions were involved in immunity pathways including tumor-necrosis factor, which plays an important role in EEHV response. Genomic sequences of African bush, forest, and Asian elephant genomes revealed extensive sequence conservation at TP53 retrogene loci across three species, which may be related to TP53 functionality in elephant cancer resistance. Positive selection scans revealed outlier genes related to additional elephant traits. Our study suggests that gene regulation plays an important role in the differential inflammatory response of Asian and African elephants, leading to increased infectious disease and cancer susceptibility in Asian elephants. These genomic discoveries can inform future functional and translational studies aimed at identifying effective treatment approaches for ill elephants, which may improve conservation.

Cancer risk across mammals

“…While a few studies aimed to establish cross-species variation in cancer risk 15 , 16 , most estimates and analyses have considerable limitations. These include small cross- or within-species sample sizes 1 , 6 , 17 , lacking information on the age distribution of cancer 15 – 17 , data heterogeneity (for example, biases due to domestication 17 or combining data from multiple taxa 17 , 18 ) or lack of control for phylogenetic relatedness among species 17 . Moreover, the effect of longevity was generally tested using the much-debated metric of maximum reported lifespan 15 – 17 .…”

Aging: What We Can Learn From Elephants

“…Humans have one copy of TP53, whereas savanna, forest, and Asian elephants are estimated to have 19-23, 21-24, and 19-22 TP53 copies, respectively (Tollis et al, 2020). This is compared to estimates of 19-28, and 22-25 TP53 copies in the extinct woolly mammoth and straight-tusked elephant, respectively (Tollis et al, 2020). Other afrotherian species, such as the manatee and rock hyrax, have two copies of TP53, while Bowhead and Minke whales each have one, respectively (Sulak et al, 2016).…”

Understanding Mycobacterium tuberculosis complex in elephants through a One Health approach: a systematic review

“…The global distribution of wild or free-ranging elephants includes 27 countries, 13 in Asia and 14 in Africa [ 7 ]. Three elephant species are recognized, the Asian elephant, the African savanna elephant, and the African forest elephant ( Loxodonta cyclotis ) [ 8 ]. Among the Asian countries, India has the greatest number of elephants and the highest number of human TB cases [ 9 ].…”