正选择驱动小反刍家畜重复基因的多样性变化
发布时间：2022-02-24 13:06
脊椎动物共经历了两次全基因复制。现有研究认为,基因复制是生物表型多样化的基础。基因复制提供了新的拷贝,这些拷贝在正选择的作用下形成新的基因。在复制后基因的命运有两种:其中一些失去功能变成伪基因,另一些则被保留下来形成新基因。这些新基因可能维持了原有的功能,也可能获得了新功能。在小反刍家畜中,人们对迄今为止所有的功能基因究竟是如何分化的,又是如何适应家养环境的还知之甚少。因此,我们对小型反刍动物中发生了复制事件的功能基因的选择信号和适应性进化展开研究,以期将遗传变异与表型联系起来,从而在有限的资源条件下提高家畜生产力。1.MC1R基因的适应性进化为山羊种群分化提供了证据基因复制及随后的功能分化是适应性进化的基本过程,它导致了―同源不同功‖的基因家族的形成。目前选择对中国地方山羊群体表型多样性形成的影响机制尚不清楚。因此,本研究探讨了中国地方山羊群体在驯化过程中发生在复制后的功能基因上的适应性选择。为了检测中国地方山羊群体中重要经济性状的基因正选择信号,我们用直接测序法检测了五个中国地方山羊群体中12个与重要经济性状相关的基因,检测到13个SNP位点,根据SNP位点的等位基因频率计算Fst...
【文章来源】：华中农业大学湖北省211工程院校教育部直属院校
【文章页数】：247 页
【学位级别】：博士
【文章目录】：
摘要
ABSTRACT
List of abbreviations
CHAPTER 1 General Introduction
1.1 Animal Domestication
1.2 Molecular Genetics and Evolution
1.3 Evolution of Animal Domestication
1.4 Domestication History:From Traditional Farming to Modern Breeding
1.5 Domestication Driving Diversification
1.6 Tracing Diversifying Selection under Domestication and Migration
1.6.1 DNA markers reveal the complexity of livestock selection signatures
1.6.2 Detecting diversifying selection in genomic data
1.6.3 Gene duplication drives diversification
1.6.4 Rapid molecular evolution at individual loci
1.6.5 Evidence of positive selection in human genome
1.6.6 Mapping signatures of positive selection in livestock
1.6.7 Connecting DNA with diversification and selection
1.7 Tracing Functional Genomic Variation and Selection
1.7.1 Candidate gene approach and genetic association
1.7.2 Genome wide scans of positive selection
1.7.3 Population differentiation index(FST)
1.7.4 Advantageous alleles and selective sweeps
1.7.5 Adaptive evolution in proteins coding genes in mammals
1.7.6 Rapidly evolving proteins
1.7.7 Positive selection favors amino acid replacements
1.7.8 Positive selection and gene expression noise
1.8 Relationship between Gene mutation and Protein structure
1.9 Amino Acid Properties Conserved in Molecular Evolution
1.10 Vertebrate Pigmentation:From underlying Genetics to Diversification
1.10.1 Genes/alleles associated with pigmentation
1.10.2 Genetics of pigment variation
1.10.3 Geographic distribution of UV radiation
1.10.4 Pigmentation as an adaptation to UV radiation
1.10.5 Melanogenesis
1.10.6 Underlying molecular genetics
1.11 Chinese Indigenous Goat and Sheep Populations
1.11.1 Goat populations
1.11.2 Sheep populations
1.12 Scientific Questions
CHAPTER 2 Adaptive evolution of MC1R gene reveals the evidence for diversifying selection in goat
2.1 Introduction
2.2 Materials and Methods
2.2.1 Ethics statement
2.2.2 Animals selection
2.2.3 Sample collection and DNA extraction
2.2.4 Genotyping and polymorphism
2.2.5 Positive selection analysis
2.2.6 Evolutionary analysis of diversifying selection
2.2.7 Protein structure and ligand prediction
2.2.8 Ligand dataset preparation
2.3 Results
2.3.1 Positive selection of MC1R gene by FDIST analysis
2.3.2 Evolutionary analysis of diversifying selection
2.3.3 Evolutionary finger printing of MC1R gene
2.3.4 Consensus sequences of MC1R gene
2.3.5 Epigenetic predictions for MC1R
2.3.6 3D structure predictions and modeling
2.4 Discussion
CHAPTER 3 Adaptive evolution of TYRP1 and TYRP2 genes reveals signatures of selection in sheep populations at different altitude environment
3.1 Introduction
3.2 Materials and Methods
3.2.1 Ethics statement
3.2.2 Experimental animals
3.2.3 DNA extraction and construction of DNA pool
3.2.4 Primer designing and PCR
3.2.5 Sequencing and genotyping
3.2.6 Positive selection analysis
3.2.7 Sequence analysis of selective forces on TYRP genes
3.2.8 Evolutionary analysis of diversifying selection
3.2.9 Phylogenetic analysis
3.2.10 Protein structure prediction
3.2.11 Statistical analysis
3.2.12 Association and population difference analysis between allele frequency and altitude
3.3 Results
3.3.1 Positive selection of TYRP1 and TYRP2 genes by FDIST analysis
4.3.2 Evolutionary evidence of positive selection
3.3.3 Evolutionary analysis of diversifying selection
3.3.4 Phylogenetic analysis
3.3.5 Consensus sequences of TYRP1 and TYRP2 genes
3.3.6 CpG island predictions for TYRP1 and TYRP2 genes
3.3.7 3D structure predictions and modeling
3.4 Discussion
CHAPTER 4 Mutational mapping of Tyrp1 gene infer integrating functional evolution for sheep altitude adaptation
4.1 Introduction
4.2 Materials and Methods
4.2.1 Ethics statement
4.2.2 Experimental animals
4.2.3 Characterization of the sheep TYRP1
4.2.4 Association study between genotypes and pigmentation phenotypes
4.2.5 Gene synthesis and amplification
4.2.6 Plasmid construction
4.2.7 Cell culture and transfection
4.2.8 Protein extraction and western blot analysis
4.2.9 Tyrosinase Enzymatic Assays
4.2.10 Retrieval of sheep tyrosinase sequence and analysis
4.2.11 3D protein modeling and structural analysis of sheep tyrosinase
4.2.12 Conservation of amino acids
4.2.13 Residual mutation analysis of mutated tyrosinase
4.2.14 Prediction of post translation modification sites
4.2.15 Protein stability prediction
4.2.16 Prediction of structural effect of point mutation on TYRP1
4.2.17 Prediction of protein ligand binding site and docking analysis
4.2.18 KEGG enrichment analysis
4.3 Results
4.3.1 Western blot analysis
4.3.2 Enzyme activity assay
4.3.3 Sequence analysis of sheep tyrosinase
4.3.4 Amino acid composition and disordered segment prediction
4.3.5 Structures prediction and assessment of mutated sheep tyrosinase
4.3.5 Structures prediction and docking studies
4.3.6 Analysis of physicochemical characteristics of predicted structures
4.3.7 Cross-correlation analysis of mutated structures
4.3.8 Prediction of structural effects of point mutation on tyrosinase
4.3.9 Prediction of functional effects and structure stability
4.3.10 Prediction of ligand binding sites and interaction of amino acids with ligands
4.3.11 Protein movement analysis
4.3.12 Melanogenesis and Tyrosine metabolism pathway analysis
4.4 Discussion
CHAPTER 5 Signatures of positive selection in BMP15 and GDF9 genes modulating ovarian function in mammals
5.1 Introduction
5.2 Material and Methods
5.2.1 Sequence analysis and data set preparation
5.2.2 Codon based positive selection analysis
5.2.3 Protein-protein interaction network analysis
5.3 Results
5.3.1 Positive Selection on Amino Acid Positions
5.3.2 Consensus sequences of BMP15 and GDF9 genes
5.3.3 Protein-protein interaction network
5.4 Discussion
CHAPTER 6 Conclusions,innovations and future directions
6.1 Conclusions
6.2 Innovations
6.3 Future directions
References
Acknowledgement
List of Publications
Appendices
本文编号：3642784
【文章来源】：华中农业大学湖北省211工程院校教育部直属院校
【文章页数】：247 页
【学位级别】：博士
【文章目录】：
摘要
ABSTRACT
List of abbreviations
CHAPTER 1 General Introduction
1.1 Animal Domestication
1.2 Molecular Genetics and Evolution
1.3 Evolution of Animal Domestication
1.4 Domestication History:From Traditional Farming to Modern Breeding
1.5 Domestication Driving Diversification
1.6 Tracing Diversifying Selection under Domestication and Migration
1.6.1 DNA markers reveal the complexity of livestock selection signatures
1.6.2 Detecting diversifying selection in genomic data
1.6.3 Gene duplication drives diversification
1.6.4 Rapid molecular evolution at individual loci
1.6.5 Evidence of positive selection in human genome
1.6.6 Mapping signatures of positive selection in livestock
1.6.7 Connecting DNA with diversification and selection
1.7 Tracing Functional Genomic Variation and Selection
1.7.1 Candidate gene approach and genetic association
1.7.2 Genome wide scans of positive selection
1.7.3 Population differentiation index(FST)
1.7.4 Advantageous alleles and selective sweeps
1.7.5 Adaptive evolution in proteins coding genes in mammals
1.7.6 Rapidly evolving proteins
1.7.7 Positive selection favors amino acid replacements
1.7.8 Positive selection and gene expression noise
1.8 Relationship between Gene mutation and Protein structure
1.9 Amino Acid Properties Conserved in Molecular Evolution
1.10 Vertebrate Pigmentation:From underlying Genetics to Diversification
1.10.1 Genes/alleles associated with pigmentation
1.10.2 Genetics of pigment variation
1.10.3 Geographic distribution of UV radiation
1.10.4 Pigmentation as an adaptation to UV radiation
1.10.5 Melanogenesis
1.10.6 Underlying molecular genetics
1.11 Chinese Indigenous Goat and Sheep Populations
1.11.1 Goat populations
1.11.2 Sheep populations
1.12 Scientific Questions
CHAPTER 2 Adaptive evolution of MC1R gene reveals the evidence for diversifying selection in goat
2.1 Introduction
2.2 Materials and Methods
2.2.1 Ethics statement
2.2.2 Animals selection
2.2.3 Sample collection and DNA extraction
2.2.4 Genotyping and polymorphism
2.2.5 Positive selection analysis
2.2.6 Evolutionary analysis of diversifying selection
2.2.7 Protein structure and ligand prediction
2.2.8 Ligand dataset preparation
2.3 Results
2.3.1 Positive selection of MC1R gene by FDIST analysis
2.3.2 Evolutionary analysis of diversifying selection
2.3.3 Evolutionary finger printing of MC1R gene
2.3.4 Consensus sequences of MC1R gene
2.3.5 Epigenetic predictions for MC1R
2.3.6 3D structure predictions and modeling
2.4 Discussion
CHAPTER 3 Adaptive evolution of TYRP1 and TYRP2 genes reveals signatures of selection in sheep populations at different altitude environment
3.1 Introduction
3.2 Materials and Methods
3.2.1 Ethics statement
3.2.2 Experimental animals
3.2.3 DNA extraction and construction of DNA pool
3.2.4 Primer designing and PCR
3.2.5 Sequencing and genotyping
3.2.6 Positive selection analysis
3.2.7 Sequence analysis of selective forces on TYRP genes
3.2.8 Evolutionary analysis of diversifying selection
3.2.9 Phylogenetic analysis
3.2.10 Protein structure prediction
3.2.11 Statistical analysis
3.2.12 Association and population difference analysis between allele frequency and altitude
3.3 Results
3.3.1 Positive selection of TYRP1 and TYRP2 genes by FDIST analysis
4.3.2 Evolutionary evidence of positive selection
3.3.3 Evolutionary analysis of diversifying selection
3.3.4 Phylogenetic analysis
3.3.5 Consensus sequences of TYRP1 and TYRP2 genes
3.3.6 CpG island predictions for TYRP1 and TYRP2 genes
3.3.7 3D structure predictions and modeling
3.4 Discussion
CHAPTER 4 Mutational mapping of Tyrp1 gene infer integrating functional evolution for sheep altitude adaptation
4.1 Introduction
4.2 Materials and Methods
4.2.1 Ethics statement
4.2.2 Experimental animals
4.2.3 Characterization of the sheep TYRP1
4.2.4 Association study between genotypes and pigmentation phenotypes
4.2.5 Gene synthesis and amplification
4.2.6 Plasmid construction
4.2.7 Cell culture and transfection
4.2.8 Protein extraction and western blot analysis
4.2.9 Tyrosinase Enzymatic Assays
4.2.10 Retrieval of sheep tyrosinase sequence and analysis
4.2.11 3D protein modeling and structural analysis of sheep tyrosinase
4.2.12 Conservation of amino acids
4.2.13 Residual mutation analysis of mutated tyrosinase
4.2.14 Prediction of post translation modification sites
4.2.15 Protein stability prediction
4.2.16 Prediction of structural effect of point mutation on TYRP1
4.2.17 Prediction of protein ligand binding site and docking analysis
4.2.18 KEGG enrichment analysis
4.3 Results
4.3.1 Western blot analysis
4.3.2 Enzyme activity assay
4.3.3 Sequence analysis of sheep tyrosinase
4.3.4 Amino acid composition and disordered segment prediction
4.3.5 Structures prediction and assessment of mutated sheep tyrosinase
4.3.5 Structures prediction and docking studies
4.3.6 Analysis of physicochemical characteristics of predicted structures
4.3.7 Cross-correlation analysis of mutated structures
4.3.8 Prediction of structural effects of point mutation on tyrosinase
4.3.9 Prediction of functional effects and structure stability
4.3.10 Prediction of ligand binding sites and interaction of amino acids with ligands
4.3.11 Protein movement analysis
4.3.12 Melanogenesis and Tyrosine metabolism pathway analysis
4.4 Discussion
CHAPTER 5 Signatures of positive selection in BMP15 and GDF9 genes modulating ovarian function in mammals
5.1 Introduction
5.2 Material and Methods
5.2.1 Sequence analysis and data set preparation
5.2.2 Codon based positive selection analysis
5.2.3 Protein-protein interaction network analysis
5.3 Results
5.3.1 Positive Selection on Amino Acid Positions
5.3.2 Consensus sequences of BMP15 and GDF9 genes
5.3.3 Protein-protein interaction network
5.4 Discussion
CHAPTER 6 Conclusions,innovations and future directions
6.1 Conclusions
6.2 Innovations
6.3 Future directions
References
Acknowledgement
List of Publications
Appendices
本文编号：3642784
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