Decipher The Genetic Mechanism Of Temperature Adaptation In Dogs At The Whole Genome Era

The origin and evolution of domesticated animals always be the hot topics for the evolutionary biologists.“The Origin of Species” from Charles Darwin mentioned that domesticated animals are under the natural selection and artificial selection.It is an important part in evolutionary biology to explore the genetic mechanism of environmental adaptive evolution.Within the post genome era,evolutionary biologists try to study the molecular evolution mechanism of environmental adaptation and artificial selection in domesticated animals from multi-level such as the genome,transcriptome and proteome and so on.They expect to uncover the mystery of this Darwin problem.This is important for understanding biological evolution.The dog(Canis familiaris)is the earliest domesticated animals.It originated from once domestication from the gray wolf on the Eurasian continent before 15,000 to 40,000 years,and then spread to all around the world following human migrations.So its migration track recorded the history of human migration.Exploring the migration of dog helps us to understand "where to go".Additionally,different with the long-term evolution of wild animals,domesticated animals quickly adapted to various environment around world in thousands of years.Comparing with other domesticated animals,dogs have the closest relationship with humans and they lived the most similar environment.Studying the environmental adaptive evolution of dogs deepen our understanding of biological evolution.In the first part of this paper,we performed whole-genome sequencing for 15 Nigerian indigenous dogs(NID)and four African golden wolves(AGW)(Canis anthus),and then combined our data with the published data of 29 domesticated dogs and seven Eurasian grey wolves.The results of principal component analysis,phylogenetic tree and population structure analysis all revealed that NID have independent genetic components.That indicate they are a distinct population.The genetic diversity and effective population size of NID are the lowest among the major dog groups.That suggests dogs arrived in Africa later than in Eurasia.Demographic history revealed the ancestors of these dogs migrated into Africa from Eurasia befroe14,000 years and underwent a severe founder effect before population expansion.Admixture analysis further revealed that African dog genomes contain ca.1.88%-3.50% introgression from AGW.Whole-genomic scans identified 50 positively selected genes(PSGs)inked with immunity,angiogenesis,ultraviolet protection,as well as insulin secretion and sensitivity et al.Gene ontology(GO)revealed PSGs were significantly clustered in seven GO terms.Two of the terms are also enriched in the GO analysis used PSGs in African human.That suggested the convergent evolution between African human and dogs.One of the PSGs,adhesion G protein-coupled receptor E1(ADGRE1)has been found to be association with severe malaria resistance in African humans.We used coalescent simulation to exclude the possibility that the selection signal of ADGRE1 gene is due to genetic drift.So we carried further study about ADGRE1.Through the experiment of parasite infection in the mice macrophage cell,we confirmed that the ADGRE1 of dogs be association with phagocytosis of Plasmodium parasites,and increased the expression of type I interferon pathway related gene to against plasmodium infection.A specific non-synonymous mutation of ADGRE1 in African dogs(G655A)enhances its function in the anti-malaria.Besides pathogenic microorganism,temperature plays an important role in species distribution and phenotypic differences.In the second part,we study the adaptive evolution to temperature in dogs.We study the adaptation to the warm environment from southern Chinese dogs.We used three methods to detect the PSGs based on the genome of 12 gray wolves and 32 southern Chinese dogs.Among PSGs,Carnitine Palmitoyltransferase 1A(CPT1A)is the key enzyme in the long-chain fatty-acid oxidation,and have been identified to be related with the cold environment or hat-fat diet in Arctic human populations.Furthermore,a mutation,3'UTR 477 T of CPT1 A,is special in Southern Chinese dogs.And then we explore its Eurasian distribution that its frequency positively related with annual temperature.Furthermore,we confirmed miRNA miR-139 binding at this site and suppressing CPT1 A expression.Additionally,3'UTR 477 T is more affected by miR-139 compare with 477 C.So we infer CPT1 A gene is related with the temperature adaptation of dogs.Then we inferred the selective intensity of 477 T in southern Chinese dogs is 0.0044,and the age of selection was estimated at 7,962 years ago.Around 8,150 years ago,the little ice age ended and global temperatures began to rise.The warm period lasted until 1,500 years ago.Therefore we speculate that the 477 T mutation may be associated with warmer environmental adaptation.In summary,the two parts of this paper focus on the molecular mechanism of the dogs adaptive evolution in the genomic level.That provides a reference for studying the genetic mechanism that domestic animals rapidly adapted to different environments under artificial selection and natural selection.On the one hand,we deeply explored the molecular basis of the adaptation to the tropical environment in African indigenous dogs.For the first time,we discovered the function of ADGRE1 gene in the fight against malaria.This supports the dog as a model for human malaria control and treatment.On the other hand,we found the molecular mechanism of dog adaptation to warm environment.That promotes our understanding of the adaptive evolution of dogs and provides a support and inspiration for better understanding of human evolution.