A B C D E F

I H G J K L M

D E F G H I J K L M

translocation

A B C

A B C D E F G

G H I J K L M

inversion

Chromosome-level Mutation

Processes of Gene Rearrangement

A B C D E

A D C B E

B A C D E

A B C E

A B C D

A B C D C D E

interstitial deletion

paracentric inversion

pericentric inversion

duplication

terminal deletion

breakage

A B C D E

Eliminate

A B C D E F

Translocation Centric fusion

W X Y Z

A B C X Y Z

W D E F

Z Y X C D E F

Exchange of Genetic Information

Synteny : Occurence of two or more genes on a chromosome.

Conserved Synteny : Synteny of orthologous genes between species.

Terms for Comparing Gene Order

Ambystoma Linkage Map

E20A120.0

A56.721.2

A32.1937.1

G2M1745.0

A16.951.1

Gapdh63.1

E24C666.7

E5G1171.9

A36.880.1

E17C1187.8

E16A1294.7

E23C595.9

A38.3102.0

cntg26107.8

A20.2 UBC549115.3

E24C10126.3

E20C6153.8

E6G8 E22E10160.6

A40.5172.3

A11.8182.9

A9.9185.7

E7G8188.5

E20G12212.7

A21.8215.2

A19.9217.7

E8C10222.9

E21G9224.0

E20A6235.2

E18E8241.3

E10C9 E10C9

E19C4 E8C1

242.6

E11G12244.8

E13C8247.1

E16E3 G1C5248.3

E19C1260.5

A10.3276.1

A38.2278.9

A55.8286.7

A53.10292.1

E22C12297.8

E13C10313.1

E15E5326.4

E7A6342.4

E20G3352.4

A21.11357.8

A52.16380.3

A20.11388.1

E13E11396.0

E18C5401.0

E12A5 E14G1409.6

E12C9414.4

E16C5419.0

A16.1 A18.6421.6

A53.2429.6

A33.4445.5

E19E4461.4

Hoxc10477.0

E18A10 E18A12487.1

E23G3489.7

E9E7507.9

A24.2510.7

Wnt1516.1

E21G8534.2

cntg116544.6

A40.4561.9

E5C5564.7

E16C6569.3

E12C6570.5

E20C7576.4

E9C4597.8

A55.10609.5

A34.6614.8

A6.1627.2

A12.9647.8

A37.3652.7

A38.4657.9

A32.20666.0

A6.8679.5

A52.4692.6

A4.7700.4

A55.9708.3

A8.10717.3

ETG990729.6

E13E4 NT001CB10734.6

E24E9735.7

E24G7742.4

E13G1747.2

E6C6755.4

E22A7766.5

E13A5772.9

E12C8780.5

E24E3798.9

E11C1 E7C12803.4

E10A4806.9

G2I16815.5

E14C7828.1

E19C7836.7

LG1

E9E90.0

A21.419.4

E10C625.8

E23A728.2

E11E735.3

G1L747.0

E11G7 g1-e1252.2

A8.1255.4

E16G12 A6.758.3

Cspg287.6

E24E1092.4

G1-J2097.0

A6.9102.3

A12.11117.8

E11G8135.7

E14E6146.1

E14C5151.6

E7G11167.5

E6C12168.6

E9G2173.1

A29.10193.0

A9.3 UBC608.1208.5

E20A10226.4

A52.11232.1

Slc4a5235.3

A26.7244.4

E19A9260.3

E26G7264.4

E7C6265.7

E20G10293.2

E10C5 E26G3301.1

E25C12310.8

E23A12314.4

A2.2333.7

A31.3352.0

A28.5364.8

A29.2383.0

E20A2401.8

E23E3404.1

E20A5413.8

E15A11419.8

E17E6453.6

E9E1463.3

E17A10466.9

E25E1472.6

E17E10473.7

E21G10479.6

E15C4487.1

E12C5498.9

A29.4 A36.2516.7

E20A9539.2

E8E9553.9

E13A1558.8

E20G6579.1

E23E12595.2

A31.1622.6

E19E7638.5

A15.3651.6

A12.5654.1

A32.13661.5

G2I21675.7

A39.12684.6

E15A2695.3

E24C11704.1

E14G11720.3

E9E6738.5

A5.9749.5

A21.3757.2

A45.2767.6

LG2

A45.50.0

A45.315.5

E9E322.0

E21C823.4

E23G833.4

E21A450.3

E13A1184.4

Rho111.9

E12A3117.5

E7G12126.9

E10E9129.1

E19A10130.3

E15E6138.8

A1.13149.2

E10E2157.2

E21A3164.1

GNAT1171.6

E20C5182.1

E18C6189.9

E18C7194.7

E8C9197.0

E28A6205.0

E12E6206.1

E17G3217.8

E9G8223.4

E16E8235.2

A5.3238.0

A8.8246.6

A25.8 A40.7255.8

Foxa3258.4

E8A9 E24E4262.2

E23C10264.6

E18G2265.9

E14C12267.1

E16G10269.4

E15G5 E6E2

E9G12 E25C2

E29A6

275.6

E10G4 E12A8

E6G4 Calm3

280.2

E19A4281.4

E17E9 E21A5293.6

E13G5 E7A8

E9G11

294.7

A11.7298.2

A24.5306.4

E6C5 E7G7311.8

E18G5315.3

E18C8321.4

E7G2322.6

ctg325333.2

E18E7 E5E4

E5E6

343.2

A32.17365.1

A34.5383.6

E10G12 E7C10413.2

E6C2420.7

E16G1427.0

E19G10431.7

E7C8438.9

E17G8445.7

E10A8450.1

E22G5 E25G1455.3

A5.8458.0

A18.12473.4

A15.8494.6

A14.7497.1

A9.11499.5

A12.7501.9

A18.8509.5

E18G10527.9

E10A12 E18A3531.7

E15E2546.7

HLP1557.3

Hoxa4 Hoxa9564.9

E6C8589.5

A52.9604.2

A4.10614.6

E17E8643.0

E13E5 E19G3

E20E2

646.5

E12C2647.7

betaTH661.4

A56.8671.3

LG3

E9A20.0

E8A11.2

E5A86.9

E25E312.7

E23A116.2

A27.124.2

A4.636.9

E24A1165.3

E14C8 E19G271.1

E13E776.1

E6C777.3

A32.985.0

A19.10102.8

A20.18107.8

E20C1119.1

A38.9139.1

A54.5146.4

A24.6162.8

UBC274176.2

UBC134180.7

E14A11 E19A2188.1

E8C8190.5

E25A8196.8

E24A12204.3

E14A7211.7

CoxV1b223.7

E12C7224.8

E10G3229.6

E18A4233.2

ETG93235.5

E13E2242.5

E12E12 E8E1243.7

E14G10250.6

E16G9267.7

E16A7287.8

E23E9295.9

E6E5 E8A10301.8

E26G10306.6

E23G7312.4

E9A3330.5

E7C5336.6

E12E11345.4

E11G6362.3

bl005ba01392.9

E5G10398.6

E23C6405.7

E8E5408.1

E17C2413.9

E5E7416.3

A1.1435.4

A25.9443.1

A45.1445.7

A37.1453.0

E15A1469.4

E14G12478.8

E19C8495.3

E12E2 E18C3502.4

E10C1503.6

E10C11519.2

E16A9527.1

cntg66531.8

E16G8538.9

LG4

A11.90.0

A39.1013.1

A57.331.9

E14E1039.7

E12A652.6

E15E1263.3

E12A1181.1

E11G1186.2

A32.696.0

E17E4101.4

E16C7 E9C9112.3

E22E3116.9

E9A6119.5

E5G5123.1

A15.7133.5

A56.9146.7

E11G4155.6

E17C12162.6

E10C3181.8

E20A8198.4

E7A11203.0

E12G1 E12G7207.6

E22G12212.3

E13E6 E14E8213.5

g1-d5217.5

Hoxd11 Hoxd8227.0

E13A7230.4

E23G2231.6

E26A8245.6

E14E2263.1

E26C11281.3

E24C3294.9

A31.8300.5

A30.16305.8

A39.8323.1

LG5

E12G20.0

E24G1110.3

E7C134.3

E9A1145.2

E19E551.5

E24C1257.6

E14A1 G2-L2161.3

E13C783.4

G1-I897.5

E7C4 E24G398.8

E24G999.9

E17C1107.5

A39.5113.2

E14A2119.1

E13G4139.1

E10G8 A52.8155.3

G2F2158.0

E14E3177.5

E17G4186.7

E15E9190.1

A32.14195.4

A50.4210.9

A18.7221.3

G2G14229.4

E23E11241.0

E25G7251.7

E9E11 brachyury258.6

E15A6268.7

E12G12270.0

E8A7292.1

E16C8293.3

E14C3294.4

E13G11 G1D6308.6

LG6

A11.30.0

A17.67.6

A17.1012.6

A39.717.9

E26G925.8

E13A341.4

A25.661.9

A26.375.4

A20.1391.3

E12C496.7

E22C3102.8

E11E11 E12C1

E16E10

113.4

E12G10120.6

A40.2129.0

A9.4136.8

A7.14142.1

A7.10158.0

A25.10160.5

E12A7178.4

E11G2 E17A2

E19G7

186.3

A9.1189.0

E15G9191.7

E21G12207.7

E13C1212.8

E15C8 E22A3216.4

A20.8221.8

E9E10239.7

E18E11260.3

v2p3a5261.5

E16E2263.9

E7G9273.8

E6A11278.8

A27.2284.9

A54.6287.4

A28.3294.9

LG7

E14A80.0

E8A213.9

E7G1015.1

E29C419.7

E14G320.8

E15G1025.7

E12A136.4

A26.439.3

A1.647.0

E16C1260.5

E20C864.1

E19A1165.3

E15E3 E17G2

E19A12 v2p3b1

E24C7

66.5

E16A579.6

E16C385.2

E10A386.5

E10G1087.8

E12E1089.2

E13E891.7

E18C1096.3

pcna106.3

E21E4124.2

E11A8128.0

E7C9148.6

E14C4 E14G7166.2

A37.5174.3

A38.8179.2

A9.13181.9

A14.5201.8

A33.10216.9

E27E7231.2

E12A9 E7A1255.4

E14E1265.2

E7A3270.2

A19.13290.1

LG8

A19.110.0

E27A35.1

E24A122.5

ntf330.9

E17C943.4

Wnt5B58.1

E8E259.3

E30G661.7

E6G1078.4

E6E1286.6

G2-K2105.8

E19C9107.5

E12A4112.6

E9A7119.8

E20G2 E8G1121.0

E17C6125.7

E17C5 E8G11129.2

E23G6136.5

E20G5151.9

E10E3154.3

E19E8155.5

E23G1159.0

E10G2 E12E1

E15C7

166.4

UV170.1

E13C12 E6A12176.4

E18E3191.5

E8C7206.5

A19.17217.5

A55.11220.1

A50.1236.4

A10.6244.4

LG9

E23A100.0

E24C26.4

A28.627.0

A7.1148.2

E20C467.5

E24A675.0

E20C284.6

E20C397.0

E7A7100.5

E5G4105.3

E22A41109.0

E12C3115.0

E5G1117.5

E26G8118.7

E17G11122.2

E12G5124.7

E9E8136.3

E21C6156.9

E7G1174.7

E17A4191.0

E20E4200.2

E25A12222.9

E17G7233.3

A56.6241.0

LG10

A45.60.0

A27.35.0

GNAT2 A16.310.3

E21C721.1

E9C1141.8

G2G2160.4

E11C363.0

E20G1171.5

E17C3 E9C272.6

E9G176.2

E15A980.0

E19E1294.3

E13G895.5

E25E5107.8

E17E411112.6

E10A2 E15G4122.8

E15E10132.9

E6E11136.0

E13E9 G2H18137.2

E11C5139.7

A10.4142.8

Col1A145.7

Dlx3149.6

G1-L11162.4

E18A9167.1

E10C4 ETG1506

Krt17 Krt24

168.2

E13A8171.1

E9A10176.9

Hoxb13178.0

E22G4180.2

E6E7190.4

G2G13192.8

THRAP4194.0

Thra203.4

Rpl19218.5

A18.5229.1

A21.13234.4

LG11

E5A90.0

E9E48.7

A20.1926.0

E6G142.8

E12E351.2

UBC722.161.6

A33.1574.1

E14A695.3

E11E8117.0

E5A5130.6

A33.11147.4

A30.7166.7

A6.6177.4

A4.4185.0

E12G3202.3

E7E3211.4

LG12

A28.70.0

A31.512.8

E10C826.2

A12.431.5

A10.150.3

E20E3A56.164.2

E8G874.1

E23A278.8

A40.697.6

A8.1111.4

E24E1120.3

E13A6138.0

E24A5155.6

A11.2163.3

LG13

E7A50.0

E20E5 E7E9

ctg1459 ETG926

E26A9

31.3

ctg138132.6

A25.1147.2

A26.952.5

UBC14469.9

E17A798.0

E12C11105.0

A34.2118.1

A31.9125.5

LG14

5251 cM (~93%)

Human

Reptile

Salamander

Salamander Genome….BIG!

genome Chom. Chrom. obligatory proportionsize (Gbp) # Arms Map (cM) cM / Mb (A# * 50cM) obligatory cM/arm

Mouse 2.7 20 20 1361 0.5 1000 0.73 68.1

Rat 2.6 21 33 1749 0.7 1050 0.94 53.0

Human 3.0 23 46 3615 1.2 1150 0.64 78.6

Chicken 1.2 38 44 3800 3.2 1900 0.58 86.4

Ambystoma 30.0 14 28 5152 0.2 700 0.27 184.0

Genome-wide recombination is not proportional to chromosome # in Ambystoma

Chromosomal Distribution of Orthologous Genes

Human MouseCount 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Count 1 2 3 4 5 6 7 8 9 10 11 12 13 14chr1 1 1 6 11 0 6 3 0 3 12 5 1 2 0 chr1 2 1 2 1 2 0 0 1 1 5 3 1 1 0chr2 0 1 6 0 5 1 0 2 1 0 0 0 2 0 chr2 5 0 7 1 2 1 3 1 2 0 0 1 1 0chr3 0 0 15 1 1 0 2 5 1 0 1 1 0 0 chr3 3 1 3 7 0 0 0 2 3 6 2 0 0 0chr4 0 3 1 0 0 0 0 0 0 0 0 0 0 0 chr4 0 4 0 1 1 6 3 1 0 2 1 0 0 0chr5 7 5 0 0 0 1 0 0 0 0 0 0 0 0 chr5 2 1 5 0 2 0 0 3 0 0 0 0 0 0chr6 0 3 2 1 0 2 0 0 3 0 1 1 2 0 chr6 4 2 11 1 1 0 0 2 11 0 1 0 0 1chr7 1 0 9 0 3 0 0 2 7 0 2 0 0 1 chr7 5 0 9 8 0 0 0 0 0 0 1 0 0 0chr8 1 3 1 0 0 1 0 2 0 0 0 0 0 0 chr8 3 3 2 4 0 0 0 1 0 2 0 0 0 0chr9 0 7 0 2 0 1 3 0 0 0 0 0 0 0 chr9 5 1 3 0 0 6 2 1 1 1 1 0 1 0chr10 1 0 6 0 0 0 4 3 0 0 0 0 0 0 chr10 3 1 1 4 3 0 3 1 5 0 0 0 1 0chr11 1 0 11 2 0 0 0 1 2 0 1 0 1 0 chr11 12 1 11 3 3 0 0 6 2 0 13 0 2 0chr12 11 1 2 1 1 0 0 4 11 0 1 0 0 0 chr12 2 1 5 1 0 0 0 0 1 0 1 0 0 7chr13 0 0 0 0 0 0 0 0 1 0 0 1 0 0 chr13 0 3 4 3 0 0 0 0 2 0 0 0 1 0chr14 0 0 6 2 0 0 0 0 0 0 1 0 0 6 chr14 2 0 6 1 0 0 2 2 0 0 1 1 0 0chr15 1 1 2 1 0 8 0 0 1 1 0 0 0 0 chr15 7 4 4 0 0 2 0 0 3 0 1 0 0 0chr16 4 0 6 3 0 0 0 0 0 2 1 0 0 0 chr16 1 0 0 0 1 0 0 2 1 0 0 1 0 0chr17 7 1 7 3 2 0 0 2 0 0 12 0 0 0 chr17 2 1 5 2 0 1 0 0 1 0 1 1 1 0chr18 0 5 0 0 0 0 0 0 0 0 1 0 0 0 chr18 0 2 0 0 0 0 0 0 0 0 1 1 0 0chr19 8 0 3 15 1 0 0 1 0 0 0 0 0 0 chr19 0 3 12 2 0 1 0 0 0 0 0 0 0 0chr20 7 1 2 1 0 0 0 1 0 0 0 1 1 0 chrX 0 2 3 0 0 0 0 1 0 0 0 3 1 0chr21 0 0 0 1 3 0 0 0 0 0 0 0 0 0chr22 1 0 2 0 0 0 0 0 4 0 0 0 0 0chrX 0 2 3 0 0 0 0 1 0 0 0 3 1 0chrY 0 0 0 0 0 0 0 0 0 0 0 1 0 0

Chicken RatCount 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Count 1 2 3 4 5 6 7 8 9 10 11 12 13 14chr1 5 2 9 1 0 2 0 2 7 0 2 3 1 0 chr1 5 4 18 8 0 0 0 1 0 0 0 0 2 0chr2 1 8 8 2 0 0 1 1 0 0 3 0 0 0 chr2 2 5 0 4 0 1 0 1 1 5 0 0 0 0chr3 4 0 4 1 0 2 0 0 1 0 0 0 5 0 chr3 3 1 3 0 1 1 2 2 0 0 2 0 1 0chr4 0 4 1 0 0 1 2 0 0 0 0 0 0 0 chr4 4 0 8 1 1 0 1 1 5 0 3 0 0 0chr5 1 0 4 4 0 0 0 1 1 0 0 0 0 6 chr5 2 2 1 0 2 3 1 1 0 1 0 0 0 0chr6 0 0 1 0 0 0 3 1 0 0 1 0 0 0 chr6 2 1 4 0 1 0 0 1 0 0 1 0 1 2chr7 0 0 1 0 7 0 0 0 2 0 0 1 0 0 chr7 3 0 4 4 0 0 0 2 6 0 2 0 0 0chr8 1 1 0 0 0 0 0 0 0 11 0 0 0 0 chr8 4 0 2 3 0 5 1 1 2 1 0 0 0 0chr9 0 0 0 2 4 0 0 3 0 0 0 0 0 0 chr9 0 1 0 0 2 0 0 0 0 0 0 0 0 0chr10 1 0 0 3 0 6 0 0 1 1 0 0 0 0 chr10 10 2 8 2 0 0 0 2 1 0 7 0 0 0chr11 0 1 0 3 0 0 1 0 0 1 0 0 0 0 chr11 2 0 0 1 1 1 0 1 0 0 1 1 0 0chr12 0 0 7 0 0 0 0 0 2 0 1 0 0 0 chr12 0 1 5 0 2 1 0 1 0 1 2 0 0 0chr13 5 0 0 0 0 0 0 1 0 0 0 0 0 0 chr13 1 1 0 0 0 0 0 0 0 3 0 0 0 0chr14 1 0 9 0 0 0 0 0 1 0 0 0 0 1 chr14 0 1 0 0 0 0 0 1 1 0 0 0 0 0chr15 0 0 0 0 0 1 0 1 2 0 0 0 0 0 chr15 2 0 5 1 0 0 1 0 0 0 0 0 0 0chr16 1 0 0 0 0 0 0 0 0 0 0 0 0 0 chr16 2 0 3 1 0 0 1 2 1 0 0 0 0 0chr17 1 0 0 0 0 0 4 0 0 0 0 0 0 0 chr17 2 0 1 1 0 0 0 0 2 0 0 0 0 0chr18 6 1 4 0 0 0 0 0 0 0 0 0 0 0 chr18 2 3 1 1 1 0 0 0 0 0 1 1 0 0chr19 2 0 0 0 4 0 0 3 0 0 0 0 0 0 chr19 0 1 2 1 0 0 0 1 0 1 0 0 0 0chr20 5 1 0 1 0 0 0 0 0 0 1 0 0 0 chr20 0 0 0 0 0 0 0 0 1 0 1 0 1 0chr21 2 0 0 0 0 0 2 0 0 0 0 0 0 0 chrX 0 1 3 0 0 0 0 1 0 0 0 0 1 0chr22 0 0 0 0 0 0 0 1 0 0 0 0 0 0chr23 0 0 0 0 0 4 0 0 0 0 0 0 0 0chr24 1 0 0 1 0 0 0 0 2 0 0 0 0 0chr26 0 0 1 0 0 0 0 0 1 0 2 0 0 0chr27 0 1 0 0 0 0 0 0 0 0 5 0 0 0chr28 1 0 3 3 0 0 0 0 0 0 0 0 0 0chrZ 1 7 0 1 0 1 0 0 0 0 0 0 0 0

HUMAN

CHICKEN

MOUSE

RAT

Salamander Salamander

N = 402Refseq database size = 21,098

N = 338Refseq database size = 16,800

N = 338Refseq database size = 11,348

N = 236Refseq database size = 12,427

Number of Conserved Syntenies

Comparison #a #b

Human 69 28Mouse 82 24Chicken 52 17Rat 58 14

#a based on 2 or more orthologues

#b based on 4 or more orthologues

Spatial Distribution of Orthologous Loci :Segmental Homology

Lg1 Lg2 Lg3 Lg14

Salamander Genome

HUMAN

GENOME(1-23)

white met melanoid

Lg1 Lg2 Lg3 Lg14

Salamander Genome

CHICKEN

GENOME(1-23)

Conserved Synteny based upon 3 or more genes

white met melanoid

Candidate Genes

met

white

sex

melanoid

Cross-Referencing

Primary Mechanism of Duplication : Unequal Crossing Over

Crossing overBetween Daughter

Strands

Addition (duplication)

Deletion

(tandom duplications)

Crossing overBetween Daughter

Strands

Addition

Deletion

Concerted Evolution

• Members of a gene family evolve in concert.

– Mutations are transferred among members of the family (homogenization)

– Mutations are spread to all individuals in the population (fixation).

Fate of Duplicated Loci

(1) Both copies retain original functione.g. rRNA genes

(2) Gain new function through mutation and selectione.g. globin genes

(3) Become functionless pseudogenese.g globin genes

Duplication

Speciation

TD

TS

and are said to be paralogous genes

species1 and species2 are said to be orthologous genes

Species 1 Species 2

All vertebrates but jawless fish have and

Figure 1. Phylogenetic relationship of amphibians (Xenopus and Ambystoma) to other model vertebrate

species and groups of the phylum Chordata.

Million years ago 500 400 300 200 100 0

XenopusAmbystoma

Chicken

PufferfishZebrafish

AmphioxusAgnathans

MouseHumana e

b

c

d

gf

ha = mammalsb = teleostsc = amphibiansd = amniotese = tetrapodsf = gnathostomesg = vertebratesh = chordates

H1: Two independent gene losses

H2: Duplication

Time of duplication may be estimated by observing thephylogenetic distribution of genes

Processed Pseudogene

Creation of a processed pseudogene.

Fate of a Processed Pseudogene

• Functional

Jingwei (see your book, p. 464)Human phosphoglycerate kinase (PGK)

Preproinsulin in some mammals

• Nonfunctional– Examples are known for all gene types

Polyploidization : complete genome duplication