The regulatory genome constrains protein sequence evolution: implications for the search for disease-associated genes

Development of protein sequence evolution models clearly have far-reaching implications for our understanding of cellular biology, population history, and etiology of the disease. Here we analyze the transcriptome GTEx resources to measure the effects of the transcriptome on the protein sequence evolution within the framework of multi-network. We found substantial variation between the central nervous system tissue expression effect variance on an evolutionary level, with highly variable genes in cortex indicates purifying selection is significantly larger than highly variable genes in subcortical regions (Mann-Whitney U p = 1.4 × 10- 4).

The remaining network cluster in expression observed correlation with the level of evolution, allowing the analysis of the evolution of genes in diverse physiological systems, including the digestive system, reproductive, and immune system. Importantly, the tissue where the gene reaches a maximum variance expression varied significantly (p = 5.55 × 10-284) with an evolutionary level, shows a model of tissue-anchored protein sequence evolution.

Using large-scale reference resource, we show that the model provides a network-based approach transcriptome anchored to predict the main tissue affected by developmental disorders. Using a gradient driven regression tree to model the evolution of the level under various parameters of the model, features selected account for up to 62% of the variation in the rate of evolution and provide additional support to the network model.

Finally, we investigated several methodological implications, including the importance of gene expression imputation models-rate-conscious evolution using genetic data to improve the search for genes related disease in transcriptome-wide association studies. Collectively, this study presents a comprehensive transcriptome analysis based on the various factors that can inhibit the molecular evolution and propose a new framework for the study of gene function and disease mechanisms.

 The regulatory genome constrains protein sequence evolution: implications for the search for disease-associated genes
The regulatory genome constrains protein sequence evolution: implications for the search for disease-associated genes

Optimizing primer used nuclear protein-coding genes in the phylogeny of beetles and their applications in the genus Sasajiscymnus Vandenberg (Coleoptera: Coccinellidae)

Advances in genome biology and the increasing availability of genomic resources allows developing hundreds (NPC) protein-coding nuclear markers, which can be used in phylogenetic studies. However, for lower taxonomic level, it may be more practical to select multiple loci molecules suitable for phylogenetic inference. Unfortunately, the presence of the marker NPC degenerate primers can be a major obstacle, as the amplification success rate is low and they tend to reinforce the nontargeted areas.

In this study, we optimized the five fragments NPC is widely used in phylogenetic beetle (ie, the two parts of carbamoyl-phosphate synthetase: CADXM and CADMC, topoisomerase, winged and PEPCK) by reducing the length of the site and the primary sagged a little target gene. The fifth fragment NPC and 6 other molecules amplified loci to test the monophyly of the genus coccinellid Sasajiscymnus Vandenberg. Analysis of molecular data sets us clearly supported monophyletic genera may Sasajiscymnus but confirmation with extended sampling is required.

Phenol Saturated w/ 10% water for molecular biology (Phenol Liquid w/ 10% water), 90%

83275 100 ml
EUR 6.23
Description: Part A

Phenol, Crystalline

A3651-500G 500G
EUR 179.3
Description: Ultra Pure

Phenol, crystalline

PB4112 500g
EUR 210.34

Acrylamide 3x cryst. for molecular biology, 99.9%

61346 100 Gms
EUR 5.47
Description: Part A

Phenol Equilibrated with 0.1M Citrate Buffer pH 4.5 for molecular biology w/ Stabilizer

47484 100 ml
EUR 7.39
Description: Part A

Phenol:Chloroform:Isoamyl Alcohol (125:24:1) pH 4.5 for molecular biology

17080 100 ml
EUR 19.29
Description: Part A

Phenol:Chloroform:Isoamyl Alcohol (25:24:1) pH 8.0 for molecular biology

69031 100 ml
EUR 10.4
Description: Part A

Phenol:Chloroform:Isoamyl Alcohol (49.5:49.5:1) pH 6.7 for molecular biology

79030 100 ml
EUR 20.18
Description: Part A

Phenol Crystalline pure, 99%

28104 500 Gms
EUR 3.97
Description: Part A

Phenol:Chloroform: Isoamyl Alcohol (49.5:49.5:1) pH 8.0 for molecular biology

36976 100 ml
EUR 21.07
Description: Part A

Phenol Crystalline extrapure AR, 99.5%

14892 500 Gms
EUR 4.45
Description: Part A

Lysozyme (3x cryst) ex. Egg white (Muramidase) for molecular biology, 15000U/mg

45822 1 Gms
EUR 6.3
Description: Part B

Casein, for Molecular Biology

MB279-100G 1 unit
EUR 110.77
Description: Casein, for Molecular Biology

Casein, for Molecular Biology

MB279-500G 1 unit
EUR 387.65
Description: Casein, for Molecular Biology

N,N-Methylene Bisacrylamide 3x cryst. for molecular biology, 99.5%

67320 25 Gms
EUR 3.97
Description: Part A

Sucrose for molecular biology

27580 500 Gms
EUR 4.11
Description: Part A

Urea for molecular biology, 99.5%

21113 500 Gms
EUR 6.5
Description: Part A

Xylene for molecular biology, 99.5%

45122 250 ml
EUR 2.81
Description: Part A

Glycine for molecular biology, 99.5%

64072 100 Gms
EUR 1.64
Description: Part A

Acetone for molecular biology, 99.8%

27498 500 ml
EUR 3.76
Description: Part A

Methanol for molecular biology, 99.5%

96446 500 ml
EUR 6.23
Description: Part A

Carbinol for molecular biology, 99.5%

34883 500 ml
EUR 6.23
Description: Part A

Formamide for molecular biology, 99.5%

30349 500 ml
EUR 5.82
Description: Part A

Imidazole for molecular biology, 99.5%

61510 25 Gms
EUR 5.47
Description: Part A

Chloroform for molecular biology, 99.8%

96764 100 ml
EUR 3.08
Description: Part A

Urea, suitable for molecular biology

GE1210 500g
EUR 53.1

Urea, suitable for molecular biology

GE1210-1 1
EUR 58

Urea, suitable for molecular biology

GE1210-1KG 1 kg
EUR 106.8

Urea, suitable for molecular biology

GE1210-500 500
EUR 33.1

Urea, suitable for molecular biology

GE1210-500G 500 g
EUR 76.8

Triethylamine for molecular biology, 99.5%

55221 500 ml
EUR 4.11
Description: Part A

Ficoll 400® for molecular biology

45460 5 Gms
EUR 15.6
Description: Part B

Agarose UltraPhor for molecular biology

27813 10 Gms
EUR 46.5
Description: Part B

Boric Acid for molecular biology, 99.5%

22311 250 Gms
EUR 4.04
Description: Part A

2-Mercaptoethanol ?For Molecular Biology

MB041-100ML 1 unit
EUR 9.02
Description: 2-Mercaptoethanol ?For Molecular Biology

2-Mercaptoethanol ?For Molecular Biology

MB041-500ML 1 unit
EUR 26.47
Description: 2-Mercaptoethanol ?For Molecular Biology

Triton X-100 for molecular biology

64518 100 ml
EUR 6.02
Description: Part A

MOPS Buffer for molecular biology, 99%

66043 25 Gms
EUR 10.28
Description: Part B

ACES Buffer for molecular biology, 99.5%

27907 5 Gms
EUR 5.4
Description: Part B

Vitamin B12 for molecular biology, 97%

77472 250 Mg
EUR 5.78
Description: Part B

Agarose Low EEO for molecular biology

36601 10 Gms
EUR 5.1
Description: Part B

10X MOPS Buffer for molecular biology

68078 100 ml
EUR 4.5
Description: Part B

CHAPS Buffer for molecular biology, 99.5%

21420 1 Gms
EUR 10.73
Description: Part B

HEPES Buffer for molecular biology, 99.5%

16826 25 Gms
EUR 6.3
Description: Part B

Sodium Azide for molecular biology, 99%

17782 100 Gms
EUR 5.47
Description: Part A

PIPES Buffer for molecular biology, 99%

49159 100 Gms
EUR 26.03
Description: Part B

Phenylmethane Sulphonyl Fluoride (PMSF) for molecular biology, 99%

84375 1 Gms
EUR 7.13
Description: Part B

Agarose High EEO for molecular biology

60645 25 Gms
EUR 13.8
Description: Part B

Jasmonic Acid for molecular biology, 95%

79238 25 Mg
EUR 120.9
Description: Part B

Protamine Sulfate for molecular biology, 90-110%

78349 1 Gms
EUR 22.5
Description: Part B

Oil Red O for molecular biology, 75%

23576 25 Gms
EUR 5.33
Description: Part B

Sodium Chloride for molecular biology, 99.9%

33205 500 Gms
EUR 4.52
Description: Part A

Agarose Medium EEO for molecular biology

10423 10 Gms
EUR 6.75
Description: Part B

Isopropanol (IPA) for molecular biology, 99.8%

38445 100 ml
EUR 1.71
Description: Part A

Acetonitrile (ACN) for molecular biology, 99.9%

62006 250 ml
EUR 4.93
Description: Part A

Ethidium Bromide for molecular biology, 95%

93079 1 Gms
EUR 4.58
Description: Part A

Ammonium Acetate for molecular biology, 98%

37829 100 Gms
EUR 2.12
Description: Part A

Agarose Low Melting for molecular biology

32417 5 Gms
EUR 22.5
Description: Part B

Potassium Acetate for molecular biology, 99.5%

96248 100 Gms
EUR 2.74
Description: Part A

Ammonium Chloride for molecular biology, 99.5%

16992 500 Gms
EUR 4.52
Description: Part A

Ammonium Sulphate for molecular biology, 99.5%

82126 250 Gms
EUR 4.93
Description: Part A

Potassium Chloride for molecular biology, 99.5%

84984 500 Gms
EUR 6.16
Description: Part A

Sodium Bicarbonate for molecular biology, 99.7%

36328 500 Gms
EUR 5.47
Description: Part A

Glycerol (Glycerine) for molecular biology, 99.5%

62417 100 ml
EUR 2.05
Description: Part A

2-Mercaptoethanol for molecular biology, 99%

83759 100 ml
EUR 5.27
Description: Part A

Acriflavine Neutral for molecular biology, 98%

42428 5 Gms
EUR 3.15
Description: Part B

Dichloromethane (DCM) for molecular biology, 99.9%

41512 250 ml
EUR 3.22
Description: Part A

Tetrahydrofuran (THF) for molecular biology, 99.8%

92562 250 ml
EUR 3.28
Description: Part A

Dithioerythritol (DTE) for molecular biology, 99%

53384 1 Gms
EUR 9.53
Description: Part B

Sodium chloride, suitable for molecular biology

GE0307 1kg
EUR 41.33

Sodium chloride, suitable for molecular biology

GE0307-1 1
EUR 45.2

meta-Topolin (mT) for molecular biology, 98%

68913 25 Mg
EUR 17.48
Description: Part B

L-Ascorbic Acid for molecular biology, 99.7%

14116 25 Gms
EUR 1.64
Description: Part A

HEPES Sodium Salt for molecular biology, 99%

32225 25 Gms
EUR 11.85
Description: Part B

Sucrose, GlenBiol, suitable for molecular biology

GC3201-1KG 1 kg
EUR 90

Glycogen ex. Oyster for molecular biology, 85%

49740 1 Gms
EUR 7.5
Description: Part B

D-Sorbitol Powder for molecular biology, 98%

99103 500 Gms
EUR 10.33
Description: Part A

Acetic Acid Glacial for molecular biology, 99.9%

59788 100 ml
EUR 3.56
Description: Part A

Brilliant Blue G-250 for molecular biology

64222 5 Gms
EUR 4.65
Description: Part B

Brilliant Blue R-250 for molecular biology

93473 5 Gms
EUR 4.35
Description: Part B

Propidium Iodide (PI) for molecular biology, 95%

11195 10 Mg
EUR 17.63
Description: Part B

Acriflavine Hydrochloride for molecular biology, 98.5%-105%

35188 5 Gms
EUR 4.05
Description: Part B

Polysorbate 20 (Tween 20) for molecular biology

65296 100 Gms
EUR 10.81
Description: Part A

Tris Buffer Superior for molecular biology, 99.9%

37969 100 Gms
EUR 7.59
Description: Part A

Molecular Biology Grade Water for RT-PCR

ML065-1.5ML 1 unit
EUR 7.82
Description: Molecular Biology Grade Water for RT-PCR

10X TE Buffer pH-8.0 for molecular biology

51782 100 ml
EUR 9.45
Description: Part B

10X TBE Buffer pH-8.3 for molecular biology

83170 200 ml
EUR 4.95
Description: Part B

Tris Buffer AR, ACS for molecular biology, 99.9%

71033 100 Gms
EUR 6.02
Description: Part A

10X TAE Buffer pH-8.3 for molecular biology

71989 100 ml
EUR 4.43
Description: Part B

Acrylamide 40% aq. solution for molecular biology

29787 250 ml
EUR 20.53
Description: Part A

MES Monohydrate Buffer for molecular biology, 99%

26854 25 Gms
EUR 11.03
Description: Part B

Glutathione Reduced (GSH) for molecular biology, 99.5%

11514 1 Gms
EUR 5.55
Description: Part B

DL-Dithiothreitol (DTT) for molecular biology, 98%

17315 1 Gms
EUR 5.18
Description: Part B

Trifluoroacetic Acid (TFA) for molecular biology, 99.9%

40801 100 ml
EUR 22.92
Description: Part A

Ammonium Persulphate (APS) for molecular biology, 99%

65553 25 Gms
EUR 1.64
Description: Part A

Sodium Acetate Anhydrous for molecular biology, 99%

22342 250 Gms
EUR 3.56
Description: Part A

Dimethyl Sulphoxide (DMSO) for molecular biology, 99.8%

24075 100 ml
EUR 6.02
Description: Part A

Sodium Acetate Trihydrate for molecular biology, 99.5%

88035 250 Gms
EUR 2.33
Description: Part A

Cesium Sulphate extrapure for molecular biology, 99.9%

57455 10 Gms
EUR 7.5
Description: Part B

Glutathione Oxidized (GSSG) for molecular biology, 99.5%

22151 250 Mg
EUR 22.5
Description: Part B

Guanidine Thiocyanate (GTC) for molecular biology, 99%

80272 100 Gms
EUR 5.47
Description: Part A

Cesium Chloride ultrapure for molecular biology, 99.9%

32355 25 Gms
EUR 18
Description: Part B

Sucrose, GlenBiol™, suitable for molecular biology

GC3201 1kg
EUR 41.25

Sucrose, GlenBiol™, suitable for molecular biology

GC3201-1 1
EUR 45.1

Pyridine, GlenBiol™, suitable for molecular biology with molecular sieve

GS8780 2500ml
EUR 239.63

Pyridine, GlenBiol™, suitable for molecular biology with molecular sieve

GS8780-2500 2500
EUR 249.8

Calcium Chloride Dihydrate for molecular biology, 99.5%

97080 100 Gms
EUR 2.12
Description: Part A

Diethyl Pyrocarbonate (DEPC) for molecular biology, 99%

46791 5 ml
EUR 9
Description: Part B

Pyridine, GlenBiol™, suitable for molecular biology

GS6659 500ml
EUR 230.38

Pyridine, GlenBiol™, suitable for molecular biology

GS6659-2500 2500
EUR 240.3

Pyridine, GlenBiol™, suitable for molecular biology

GS6659-500 500
EUR 95.8

Formamide, GlenBiol™, suitable for molecular biology

GS9663 100ml
EUR 46.83

Formamide, GlenBiol™, suitable for molecular biology

GS9663-100 100
EUR 48.9

Phenol Crystalline extrapure AR, ACS, ExiPlus, Multi-Compendial, 99.5%

97745 500 Gms
EUR 4.93
Description: Part A

20X SSC Buffer pH 6.9-7.1 for molecular biology

12590 200 ml
EUR 2.48
Description: Part B

Bromocresol Purple Sodium Salt for molecular biology

24836 5 Gms
EUR 2.05
Description: Part A

Guanidine Hydrochloride (GHC) for molecular biology, 99.5%

45539 100 Gms
EUR 4.79
Description: Part A

Polyethylene Glycol 8000 (PEG 8000) for molecular biology

54866 500 Gms
EUR 11.97
Description: Part A

10X Tris Buffered Saline (TBS) for molecular biology

83471 500 ml
EUR 14.7
Description: Part B

Magnesium Acetate Tetrahydrate for molecular biology, 99%

50488 100 Gms
EUR 2.74
Description: Part A

Magnesium Chloride Hexahydrate for molecular biology, 99.5%

91417 250 Gms
EUR 4.45
Description: Part A

Magnesium Sulphate Heptahydrate for molecular biology, 99.5%

74440 500 Gms
EUR 6.16
Description: Part A

Tris Hydrochloride (Tris HCl) for molecular biology, 99%

89781 100 Gms
EUR 9.37
Description: Part A

L-Lysine Monohydrate (base) for molecular biology, 99%

45976 25 Gms
EUR 37.63
Description: Part A

Agarose Low EEO Superior Grade for molecular biology

23287 10 Gms
EUR 6
Description: Part B

OORA00229-1L - Molecular Biology Grade UltraPure Water

OORA00229-1L 1L
EUR 149

OORA00230-1L - Molecular Biology Grade UltraPure Water

OORA00230-1L 1L
EUR 279

DTT (Molecular Biology Grade)

CE131 5 g
EUR 44

DTT (Molecular Biology Grade)

CE132 10 g
EUR 88

DTT (Molecular Biology Grade)

CE133 25 g
EUR 170

NAD (Molecular Biology Grade)

CE196 1 g
EUR 34

NAD (Molecular Biology Grade)

CE197 5 g
EUR 137

NBT (Molecular Biology Grade)

CE209 1 g
EUR 96

NBT (Molecular Biology Grade)

CE210 5 g
EUR 345

10X Tris-Glycine-SDS Buffer for molecular biology

57806 200 ml
EUR 3.6
Description: Part B

N,N-Dimethylformamide (DMF) for molecular biology, 99.9%

24017 100 ml
EUR 3.08
Description: Part A

Cesium Chloride extrapure AR for molecular biology, 99.9%

22966 25 Gms
EUR 14.63
Description: Part B

10X Tris-Tricine-SDS Buffer for molecular biology

37852 500 ml
EUR 9.08
Description: Part B

EDTA Disodium Salt Dihydrate for molecular biology, 99.5%

43272 100 Gms
EUR 2.26
Description: Part A

DMSO, Molecular Biology Grade

40470006-1 100 mL
EUR 108.14

DMSO, Molecular Biology Grade

40470006-2 250 mL
EUR 182.67

DMSO, Molecular Biology Grade

40470006-3 500 mL
EUR 342.49

EGTA, Molecular Biology Grade

40500028-2 50 g
EUR 130.53

EGTA, Molecular Biology Grade

40500028-3 100 g
EUR 217.78

EGTA, Molecular Biology Grade

40500028-4 500 g
EUR 734.55

EGTA, Molecular Biology Grade

40500028-5 1 kg
EUR 1119.67

EGTA, Molecular Biology Grade

40500028-6 2 kg
EUR 2070.09

BCIP (Molecular Biology Grade)

CE108 250 mg Ask for price

BCIP (Molecular Biology Grade)

CE109 1 g
EUR 82

DAPI (Molecular Biology Grade)

CE117 5 mg
EUR 40

DAPI (Molecular Biology Grade)

CE118 25 mg
EUR 133

DAPI (Molecular Biology Grade)

CE119 100 mg
EUR 281

Tris (Molecular Biology Grade)

CE237 500 g
EUR 79

Tris (Molecular Biology Grade)

CE238 1 kg
EUR 135

Tris (Molecular Biology Grade)

CE239 5 kg
EUR 608

Dimethylformamide, GlenBiol™, suitable for molecular biology with molecular sieve

GS3406 2500ml
EUR 111.53

Dimethylformamide, GlenBiol™, suitable for molecular biology with molecular sieve

GS3406-2500 2500
EUR 116.2

Chloroform : Isoamyl Alcohol (24:1) for molecular biology

85563 100 ml
EUR 8.48
Description: Part B

1X Phosphate Buffered Saline (PBS) for molecular biology

95131 100 ml
EUR 3.98
Description: Part B

Saponin ex. Quillaja for molecular biology, 9% Sapogenin

80967 25 Gms
EUR 45
Description: Part B

CHAPS (Molecular Biology Grade)

CE114 1 g Ask for price

CHAPS (Molecular Biology Grade)

CE115 5 g
EUR 97

CHAPS (Molecular Biology Grade)

CE116 25 g
EUR 319

HEPES (Molecular Biology Grade)

CE171 100 g
EUR 40

A fossil-calibrated kronogram produced by BEAST, shows the origin of the genus in the late Cretaceous period (77.87 Myr). In addition, phylogenetic informativeness profile is generated to compare the phylogenetic nature of each gene is more explicit. The results showed that COI provide phylogenetic signal is the strongest among all the genes, but PEPCK, topoisomerase, CADXM and CADMC also relatively informative. Our results provide insight into the evolution of the genus Sasajiscymnus, and also enriches the molecular source of data for further study.