Font Size: a A A

Positive Selection Drives The Diversification Of Duplicated Genes In Domesticated Small Ruminant Populations

Posted on:2019-03-10Degree:DoctorType:Dissertation
Country:ChinaCandidate:Hafiz Ishfaq AhmadFull Text:PDF
GTID:1363330572984903Subject:Animal Genetics,Breeding and Reproduction
Abstract/Summary:PDF Full Text Request
There were two whole-genome duplications in Vertebrates.The process of gene duplication is widely recognized as an important contributor to the phenotypic diversity of living organisms.Gene duplication produced copies of existing genes,which can diverge from their ancestral states and contribute to the evolution of novel phenotypes.Different processes may drive the long-term retention of duplicate genes.Many duplicated genes lose their function and become pseudogenes;the others have two fates;one maintain the function of their ancestral gene and the other acquires new function.In the small ruminant livestock,there is little known about how the functional genes have been differentiated and how adapted to the domestic environment.So,we study about the adaptive evolution and selection signatures of functional genes,duplicated in small ruminants,to link the genetic variants with the phenotypes to increase the livestock production in limited resources.1.Adaptive evolution of MC1 R gene reveals the evidence for diversifying selection in goatThe duplication of genes and their subsequent functional divergence,leading to the formation of genes families that are evolutionarily related but functionally distinct,is a fundamental process of adaptive evolution.However,the mechanism of selection resulting phenotypic diversifications among indigenous goat populations is not well understood.This study was conducted to focus on the adaptive selection on duplicated genes which may arise during domestication events in indigenous goat to provide evidences for the evolution of local goats driven by positive selection.An experimental distribution of Fst was built based on approximations of Fst for each SNP across five indigenous goats.Evolutionary analyses were inferred under maximum likelihood models,the HyPhy package implemented in the DATAMONKEY Web Server.Furthermore,adaptive selection pressure on specific codons was determined using different codon based maximum likelihood methods.Signature of positive selection in goat MC1 R was explored in individual codons.We found that MC1 R candidate gene show evidence of positive selection.The results of codon selection test displayed positive diversifying selection at the sites were mainly involved in development of genetic variations of coat color in various mammalian species.Detecting signatures of selection can provide new insights into the mechanism of contemporary breeding and artificial selection and further reveal the causal genes associated to the phenotypic variation may have been modulated by domestication events in goats.2.Adaptive evolution of TYRP1 and TYRP2 genes reveals signatures of selection in sheep populations at different altitude environmentGene duplications and functional divergences are important for the formation of novel gene functions.However,little study focused on whether the differentiation of Chinese local goats is caused by positive selection of fixed beneficial mutations(mainly non-synonymous mutations)or by random fixed neutral mutations when the environment changes.This study was designed to investigate the mechanism of altitude adaptive evolution of TYRP genes among Chinese sheep populations.We chose Plateau-type Tibetan sheep,Oura-type Tibetan sheep,Valley-type Tibetan sheep,Ujumqin sheep,Sunite sheep,Tan sheep,Guangling big-tail sheep,Small-tail Han sheep and Hu sheep as material.SNP of TYRP genes in those sheep populations by direct sequencing,association analysis between gene frequency of these loci and altitudes were detected.The difference analysis of the allele frequency was done among the different altitude sheep populations.12 species‘ TYRP1 and TYRP2 genes‘ phylogenetic tree,similarity and selection direction were performed.The selection type of TYRP genes‘ SNP sites were detected by Lositan software among 9 sheep populations.The results demonstrated that there were 21 SNP loci in TYRP1 gene,the association analysis between allele frequency and altitude found that there were 5 SNP sites‘ allele frequencies significantly correlated with altitude(p<0.05;g.11121C>T,r=0.69444;g.11124T>C,r=0.78274;g.26549C>G,r=0.75280;g.26682C>T,r=-0.75537;g.26730C>A,r=-0.71120).One locus‘ allele frequency was significant different between high-altitude and middle-altitude,lowaltitude sheep populations(p<0.05),and 3 loci‘s allele frequency was significant different between high-altitude and low-altitude sheep populations(p<0.05).One locus‘ allele frequency was significant different between high-altitude and middle-altitude sheep populations(p<0.05).There were 14 SNP loci in TYRP2 gene,while there was no variation observed in TYRP2 gene that related with elevation(p>0.05).Positive selection analysis of TYRP genes in 12 species indicated that the TYRP1 gene was under significant positive selection and TYRP2 gene was mainly under purifying selection.The positive selection test results of 35 SNP loci among 9 sheep populations showed that 5 SNP sites were under positive selection in TYRP1 gene,3 SNP sites were under balancing selection in TYRP2 gene.The polymorphism of TYRP1 gene might play an important role in the diverse coat color formation of the different-altitude sheep populations,at the same time,it might play a significant role in the strong ultraviolet adaptability of high-altitude sheep population.TYRP1 and TYRP2 genes of sheep are undergoing adaptive evolution to different altitude environment,which was under positive selection and balancing selection respectively.The positive selection of sheep‘s TYRP1 gene selected and fixed the strong UV adaptability variations directionally,so that the high-altitude sheep could adapt the strong UV environment.We described general features of duplicate evolution,which allow pinpointing the cases with unique trajectories and therefore potentially lineagespecific adaptations.3.Mutational mapping of Tyrp1 gene infer integrating functional evolution for sheep altitude adaptationNovel gene functions and associated phenotypes may arise through mutations that may alter the sequence of the gene product,and/or affect gene expression.Therefore,evolutionary studies may provide new insights into the functional evolution of duplicated genes.Tyrp1 is a duplicated copy of tyrosinase responsible for the enzymatic steps in the conversion of tyrosine to melanin.The aim of this study was to find structural and functional divergence among the wild and mutant Tyrp1 and to explore their role in mammalian evolution.We predicted the two-dimensional and three-dimensional structure of TYRP1 protein of three mutants(S46C,A486 V and A510)in sheep.Then,wild-type and three mutant sheep TYRP1 proteins were expressed in HEK 293 T cells.The effects of these mutants on protein function were analyzed by detecting the activity changes of wild-type TYRP1 and mutant TYRP1.The results show that mammalian Tyrp1 has a greater turnover number for L-DOPA than for L-Tyrosine and 5,6-dihydroxyindole-2-carboxylic acid(DHICA).Thus,enzyme activity,expressed as ?mol of substrate transformed per sec,is higher in assays using L-DOPA as substrate than those using LTyrosine and DHICA.S46 C,A486V and A510 exhibited a lower mono-phenolase activity,respectively.The relative analyses exposed that the alteration of the positively charged serine with polar threonine amino acids affect the dynamic binding position and configurational arrangement of the predicted structures of Tyrp1.Thus,the unstable structures may cause the disruption of normal function of Tyrp1 consequently disturb the pigment synthesis pathways in sheep due to UV radiation exposure at various altitude that might cause adaptive evolution.4.Signatures of positive selection in BMP15 and GDF9 genes modulating ovarian function in mammalsThe mechanism of gene duplication provides a copy evading from the selection pressure on a functional gene locus.Bone morphogenetic proteins(BMPs)and the growth differentiation factors(GDFs)play important roles in ovarian folliculogenesis and essential regulator of processes of numerous granulosa cells.These genes variations are linked to various ovarian phenotypic consequences subject to the species,from infertility to improved prolificacy in sheep,primary ovarian insufficiency in women or associated with minor subfertility in mouse.This study was designed to reveal positive selection driven by aspects related to species-specific adaptations in mammalian evolution.To study the evolving role of BMP15 and GDF9,a phylogenetic analysis was performed.To find out the candidate gene associated with prolificacy in mammals,the nucleotide sequence of BMP15 and GDF9 genes,were recognized under positive selection in various mammalian species.Maximum likelihood approaches exhibited a robust divergence and a prompted evolution as compared to other TGF? family members.Among 32 mammalian species,we identified positive selection signals in the Hominidae clade resulting to 132 D,147E,163 Y,191W,and 236 P amino acid sites of BMP15 and 162 F,188K,206 R,240A,244 L,246H,248 S,251D,253 L,254F and other amino acid sites of GDF9.The positively selected amino acid sites such as Alanine,Leucine,Arginine and Lysine are supposed to be important for signaling.Sites under the positive selection may have important effects for the functioning of the protein.Overall,our results illustrated how gene duplications from different evolutionary periods have contributed to phenotypic divergence of various mammalian species.The analysis of positive selection allows to explore the changes in gene function,which could indicate adaptive evolution and identify candidate genes for phenotypic evaluation.
Keywords/Search Tags:Domestication, Small ruminant livestock, Gene duplication, Gene diversification, Positive selection, Adaptive evolution
PDF Full Text Request
Related items