Adaptive methylation regulation of p53 pathway in sympatric speciation of blind mole rats, Spalax

Abstract

Epigenetic modifications play significant roles in adaptive evolution. The tumor suppressor p53, well known for controlling cell fate and maintaining genomic stability, is much less known as a master gene in environmental adaptation involving methylation modifications. The blind subterranean mole rat Spalax eherenbergi superspecies in Israel consists of four species that speciated peripatrically. Remarkably, the northern Galilee species Spalax galili (2n = 52) underwent adaptive ecological sympatric speciation, caused by the sharply divergent chalk and basalt ecologies. This was demonstrated by mitochondrial and nuclear genomic evidence. Here we show that the expression patterns of the p53 regulatory pathway diversified between the abutting sympatric populations of S. galili in sharply divergent chalk-basalt ecologies. We identified higher methylation on several sites of the p53 promoter in the population living in chalk soil (chalk population). Site mutagenesis showed that methylation on these sites linked to the transcriptional repression of p53 involving Cut-Like Homeobox 1 (Cux1), paired box 4 (Pax 4), Pax 6, and activator protein 1 (AP-1). Diverse expression levels of p53 between the incipiently sympatrically speciating chalk-basalt abutting populations of S. galili selectively affected cell-cycle arrest but not apoptosis. We hypothesize that methylation modification of p53 has adaptively shifted in supervising its target genes during sympatric speciation of S. galili to cope with the contrasting environmental stresses of the abutting divergent chalk-basalt ecologies.evolution | speciation | ecological stress and adaptation | epigenetics S ympatric speciation without geographic isolation is becoming more convincing with the accumulation of supportive genetic evidence (1-3). As we previously proposed (1, 3), sympatric speciation occurs during the adaptive evolution of the Israeli subterranean blind mole rat Spalax galili (2n = 52) living in the Galilee in northern Israel. Genetic and physiological differences were observed from two abutting populations of S. galili living in sharply divergent soil types (chalk and basalt) including population-specific haplotype mitochondrial (mt) DNA pattern, population-unique SNPs of genome, different activity patterns, and distinct oxygen consumption (1, 3). This is the first demonstration, to our knowledge, of sympatric speciation in subterranean mammals, certainly in the genus Spalax, which usually speciates peripatrically or allopatrically (4).The tumor suppressor gene p53 has been underappreciated for its roles in environmental adaptation. As a sensor of stresses including genotoxic stress and hypoxia (5, 6), p53 is also a master gene of diversity during adaptive evolution (7-11), although this perspective is less studied than its role in cancer suppression. Modifications of p53 in different levels during adaptive evolution confer the animal's selective advantage by regulating adaptive cell fates. Our recent study demonstrated that variation of p53 is important for ada...

Maximizing ecological and evolutionary insight in bisulfite sequencing data sets

“…DNA methylation – the covalent addition of methyl groups to cytosine bases – is a gene regulatory mechanism of well-established importance in development, disease, and the response to environmental conditions 1 – 5 . In addition, shifts in DNA methylation are thought to contribute to the speciation process and the evolution of trait differences between taxa 6 – 8 , in support of the idea that gene regulation plays a key role in evolutionary change. Because of its contribution to phenotypic diversity, interest in DNA methylation from the ecology and evolutionary biology communities is high 4 , 5 , 9 – 16 .…”

Comparative morphometric analysis of lungs of the semifossorial giant pouched rat (Cricetomys gambianus) and the subterranean Nigerian mole rat (Cryptomys foxi)

“…Between the subterranean S. ehrenbergi and the above-ground dwelling rat, Rattus norvegicus, structural and functional differences correlate with the hypoxic stress and the greater vascularization of muscle tissue 29,143,144 . Genetic adaptation to life underground has been determined in S. ehrenbergi [145][146][147] . According to Skinner and Chimimba 112 and Ewer 136 , at night, the omnivorous C. gambianus spends 67% of the time resting, 9.5% active in the burrows and 23.4% active outside: the most active times are between 1900 to 2200 hours and between 0100 to 0500 hours.…”

Transcriptomes Divergence of Ricotia lunaria Between the Two Micro-Climatic Divergent Slopes at “Evolution Canyon” I, Israel

“…As the other models in Evolution Canyon ( Sikorski and Nevo, 2005 ; Nevo, 1995 , 2014 ). Evolution Plateau ( Hadid et al, 2013 ; Li K. et al, 2015 , 2016 ; Zhao et al, 2016 ) and Evolution Slope ( Wang et al, 2018 ), sympatric speciation of R. lunaria at Evolution Canyon I in Mount Carmel could also be tested at Evolution II in western Upper Galilee, which are separated by 40 km from EC I. Future projects of R. lunaria at both EC I and EC II could include intraslope and interslope crosses, investigations on genomics, transcriptomics, epigenomics, and metabolomics, which could shed light on the complexities of sympatric speciation.…”

“…In the EC, major adaptive complexes on the tropical “African” slope [(AS), also called south-facing slope (SFS)] are related to solar radiation, heat, and drought, whereas those on the temperate “European” slope [(ES), also called north-facing slope (NFS)] are related to shade stress for photosynthesis, and interslope species divergence led to the incipient sympatric speciation in a diversity of organisms ( Pavlícek et al, 2003 ; Nevo, 2006 , 2014 ; Kossover et al, 2009 ; Yang et al, 2009 ; Li K. et al, 2016 ). This kind of local adaptation resulted from interslope microclimatic divergence also occurring in other three “Evolution Canyons” in Israel in the Galilee, Golan, and Negev Mountains as well as in the other evolution canyons worldwide ( Nevo, 2012 ), and in the extension of the Evolution Canyon model in Evolution Plateau (upper Galilee Mountains) ( Hadid et al, 2013 ; Li K. et al, 2015 , 2016 ; Zhao et al, 2016 ).…”

“…However, it required the conditions of primary divergence with gene flow between populations, with complete absence of geographic barriers, which could be uncommon in nature. Recently, a plenty of studies on animal and bacteria revealed that the formation of reproductive isolation during the sympatric speciation could be favored by natural selection, such as in sexual selection and resource competence ( Berlocher and Feder, 2002 ; Li K. et al, 2015 , 2016 ; Rosser et al, 2015 ; Dunning et al, 2016 ; Getz et al, 2016 ; Kautt et al, 2016 ; Rodriguez et al, 2016 ; Zhao et al, 2016 ). Up to date, however, there is currently very little evidence to prove that natural selection in plants could induce sympatric speciation, partially due to the fact that flowering time hardly diverged between contiguous populations.…”