Marine mammals provide a valuable model for studying the molecular basis of convergent evolution during secondary aquatic adaptation.Using multiomics data and functional experiments,including CRISPR-Cas9 mouse models ...Marine mammals provide a valuable model for studying the molecular basis of convergent evolution during secondary aquatic adaptation.Using multiomics data and functional experiments,including CRISPR-Cas9 mouse models and luciferase reporter assays,this study explored the molecular mechanisms driving this transition across coding regions,regulatory elements,and genomic architecture.Convergent amino acid substitutions in APPL1P378L and NEIL1E71G were found to promote lipid accumulation and suppress cancer cell proliferation,likely contributing to the evolution of extensive blubber layers and cancer resistance.Convergently evolved conserved non-exonic elements(CNEs)and lineage-specific regulatory variations were shown to influence the activity of nearby genes(e.g.,NKX3-2,SOX9,HAND2),shaping cetacean limb phenotypes.Additionally,convergent shifts in topologically associating domains(TADs)across cetaceans and pinnipeds were implicated in the regulation of ASXL3 and FAM43B expression,playing a role in the formation of thickened blubber layers and mitigating cancer susceptibility.Structural variations within conserved TADs were associated with the expression of neuronal genes,including NUP153 and ID4,potentially driving cognitive and social adaptations.These findings provide novel insights into the molecular foundations of the convergent evolution of secondary aquatic adaptations in mammals.展开更多
基金supported by the National Key Programme of Research and Development,Ministry of Science and Technology(2022YFF1301600)to G.Y.the Key Project of the Na tional Natural Science Foundation of China(32030011)to G.Y.+5 种基金the National Natural Science Foundation of China(32070409,32270453,32270442,32070408,and 32270441)to S.X.,W.R.,L.S.,and R.T.the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),Qinglan Project of Jiangsu Province to S.X.the Specially-Appointed Professor Program of Jiangsu Province to I.S.the Jiangsu Foreign Expert Bureau to I.S.the Jiangsu Provincial Department of Technology(JSSCTD202142)to I.S.the PI Project of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(GML2021GD0805)to G.Y.
文摘Marine mammals provide a valuable model for studying the molecular basis of convergent evolution during secondary aquatic adaptation.Using multiomics data and functional experiments,including CRISPR-Cas9 mouse models and luciferase reporter assays,this study explored the molecular mechanisms driving this transition across coding regions,regulatory elements,and genomic architecture.Convergent amino acid substitutions in APPL1P378L and NEIL1E71G were found to promote lipid accumulation and suppress cancer cell proliferation,likely contributing to the evolution of extensive blubber layers and cancer resistance.Convergently evolved conserved non-exonic elements(CNEs)and lineage-specific regulatory variations were shown to influence the activity of nearby genes(e.g.,NKX3-2,SOX9,HAND2),shaping cetacean limb phenotypes.Additionally,convergent shifts in topologically associating domains(TADs)across cetaceans and pinnipeds were implicated in the regulation of ASXL3 and FAM43B expression,playing a role in the formation of thickened blubber layers and mitigating cancer susceptibility.Structural variations within conserved TADs were associated with the expression of neuronal genes,including NUP153 and ID4,potentially driving cognitive and social adaptations.These findings provide novel insights into the molecular foundations of the convergent evolution of secondary aquatic adaptations in mammals.
