正選擇驅(qū)動(dòng)小反芻家畜重復(fù)基因的多樣性變化
發(fā)布時(shí)間：2022-02-24 13:06
脊椎動(dòng)物共經(jīng)歷了兩次全基因復(fù)制�，F(xiàn)有研究認(rèn)為,基因復(fù)制是生物表型多樣化的基礎(chǔ)�；驈�(fù)制提供了新的拷貝,這些拷貝在正選擇的作用下形成新的基因。在復(fù)制后基因的命運(yùn)有兩種:其中一些失去功能變成偽基因,另一些則被保留下來形成新基因。這些新基因可能維持了原有的功能,也可能獲得了新功能。在小反芻家畜中,人們對迄今為止所有的功能基因究竟是如何分化的,又是如何適應(yīng)家養(yǎng)環(huán)境的還知之甚少。因此,我們對小型反芻動(dòng)物中發(fā)生了復(fù)制事件的功能基因的選擇信號(hào)和適應(yīng)性進(jìn)化展開研究,以期將遺傳變異與表型聯(lián)系起來,從而在有限的資源條件下提高家畜生產(chǎn)力。1.MC1R基因的適應(yīng)性進(jìn)化為山羊種群分化提供了證據(jù)基因復(fù)制及隨后的功能分化是適應(yīng)性進(jìn)化的基本過程,它導(dǎo)致了―同源不同功‖的基因家族的形成。目前選擇對中國地方山羊群體表型多樣性形成的影響機(jī)制尚不清楚。因此,本研究探討了中國地方山羊群體在馴化過程中發(fā)生在復(fù)制后的功能基因上的適應(yīng)性選擇。為了檢測中國地方山羊群體中重要經(jīng)濟(jì)性狀的基因正選擇信號(hào),我們用直接測序法檢測了五個(gè)中國地方山羊群體中12個(gè)與重要經(jīng)濟(jì)性狀相關(guān)的基因,檢測到13個(gè)SNP位點(diǎn),根據(jù)SNP位點(diǎn)的等位基因頻率計(jì)算Fst...
【文章來源】：華中農(nóng)業(yè)大學(xué)湖北省211工程院校教育部直屬院校
【文章頁數(shù)】：247 頁
【學(xué)位級別】：博士
【文章目錄】：
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
本文編號(hào)：3642784
【文章來源】：華中農(nóng)業(yè)大學(xué)湖北省211工程院校教育部直屬院校
【文章頁數(shù)】：247 頁
【學(xué)位級別】：博士
【文章目錄】：
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
本文編號(hào)：3642784
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