Скачать презентацию Junk DNA Most human genome does not Скачать презентацию Junk DNA Most human genome does not

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Junk DNA Junk DNA

Most human genome does not encode for proteins Most human genome does not encode for proteins

Transposable elements in the human genome Transposable elements in the human genome

Transposable elements Barbara Mc. Clintock 1902 -1992 Nobel Prize in Physiology or Medicine (1983) Transposable elements Barbara Mc. Clintock 1902 -1992 Nobel Prize in Physiology or Medicine (1983)

DNA transposons and retroelements Retroelements DNA transposons DNA transposons and retroelements Retroelements DNA transposons

Transposable elements vs. genes in animal genomes Genes DNA transposons Retroelements Worm 19. 000 Transposable elements vs. genes in animal genomes Genes DNA transposons Retroelements Worm 19. 000 3. 000 600 Fruit fly 14. 000 400 1200 Oikopleura 15. 000 100 600 Fugu 31. 000 8. 000 22. 000 Chicken 23. 000 13. 000 230. 000 Mouse 30. 000 112. 000 2. 800. 000 Human 35. 000 294. 000 2. 900. 000

zebrafish eel sturgeon pike carp tilapia trout molly killifish medaka platyfish Transposable elements can zebrafish eel sturgeon pike carp tilapia trout molly killifish medaka platyfish Transposable elements can be lost without altering host fitness Rex 3 C

Orgel LE, Crick FH (1980) Selfish DNA: the ultimate parasite. Nature 284: 604 -607. Orgel LE, Crick FH (1980) Selfish DNA: the ultimate parasite. Nature 284: 604 -607.

Transposable elements can negatively affect host genes Transposable elements can negatively affect host genes

Transposable elements can cause disease Element Organism Disease Gene Mechanism L 1 L 1 Transposable elements can cause disease Element Organism Disease Gene Mechanism L 1 L 1 Alu Alu SVA L 1 IAP Human Human Mouse Haemophilia A DMD Colon carcinoma Breast cancer Haemophilia B Dent's disease Various Myoclonus Various Factor VIII Dystrophin APC BRCA 2 Factor IX CLCN 5 Various Glrb Various Insertion Insertion Insertion L 1 Alu Alu L 1 Human Human Mouse Glycogen storage dis. Hunter disease Wiskott-Aldrich sdr Lesch-Nyhan sdr Beige-like coat color PHKB IDS WASP HPRT 1 HPRT Lystbg Ectopic recombination (del) Ectopic recombination (dupl) Ectopic recombination (del) Alu Alu Human Ornithine AT def. Sly syndrome Alport syndrome OAT GUSB COL 4 A 3 Exonisation

Anticancer mutagenic insertion in the platyfish Xmrk Txi-1 Anticancer mutagenic insertion in the platyfish Xmrk Txi-1

Proposed and demonstrated functions of transposable elements Gene regulation X chromosome inactivation Telomere maintenance Proposed and demonstrated functions of transposable elements Gene regulation X chromosome inactivation Telomere maintenance (Drosophila) Gene and genome evolution / Genetic diversity …

Transposable elements are drivers of gene evolution About 4% of human genes contain sequences Transposable elements are drivers of gene evolution About 4% of human genes contain sequences derived from transposable elements in their coding region (Nekrutenko and Li 2003) About 25% of human promoter regions contain sequences derived from transposable elements (Jordan et al. 2003)

Comparative genomics of transposable elements in vertebrates Comparative genomics of transposable elements in vertebrates

Comparative genomics of transposable elements in vertebrates Comparative genomics of transposable elements in vertebrates

Transposable elements Transposable elements

Transposable elements in the human genome Transposable elements in the human genome

Many transposable elements have been lost from the mammalian lineage Many transposable elements have been lost from the mammalian lineage

Retrotransposon diversity in the fish lineage Zebrafish Non-LTR retrotransposons Penelope-like Total Fugu Tetraodon Human Retrotransposon diversity in the fish lineage Zebrafish Non-LTR retrotransposons Penelope-like Total Fugu Tetraodon Human 7 clades 6 clades 3 clades 15 clades 8 clades - 1 clade 2 clades - 23 clades 16 clades 3 clades

Ty 3/Gypsy retrotransposons Ty 3/Gypsy retrotransposons

Diversity of Gypsy/Ty 3 LTR retrotransposons in fish genomes Barthez Osvaldo Gypsy Fly Ciona Diversity of Gypsy/Ty 3 LTR retrotransposons in fish genomes Barthez Osvaldo Gypsy Fly Ciona Sea urchin Fly Gmr 1 Atlantic cod Nematode Maggy Fungus Sushi Gmr 1 L Ty 3 Yeast Ciona Trematode Fly Rex 8 Cs. Rn 1 silkworm Ciona Jule Ciona SURL 0. 1 changes nematode sea urchin SURL-like

Gypsy/Ty 3 retrotransposons in the vertebrate lineage Pufferfish Takifugu rubripes Pufferfish Tetraodon nigroviridis Zebrafish Gypsy/Ty 3 retrotransposons in the vertebrate lineage Pufferfish Takifugu rubripes Pufferfish Tetraodon nigroviridis Zebrafish Danio rerio Homo sapiens 8 5 9 0 SURL-like Jule Cs. Rn 1 Sushi Barthez Gmr 1(-like) Rex 8 Osvaldo 20 10 10 140 290 25 55 10 0 fossils 8 25 120 45 15 fossils 0 20 20 10 8 700 85 510 12 25 0 0 fossils 0 0 Total 560 213 1390 0 (fossils) Clades 0: not detected

Sequences related to gag of Sushi in mammalian genomes Sequences related to gag of Sushi in mammalian genomes

Sushi-ichi retrotransposons from fish Pro LTR RT/RNase. H Int LTR pol gag CCHC Poulter Sushi-ichi retrotransposons from fish Pro LTR RT/RNase. H Int LTR pol gag CCHC Poulter et al. 1998

Sushi-ichi pufferfish Pro RT/RNase. H Int LTR 1 kb gag LTR pol CCHC Mart Sushi-ichi pufferfish Pro RT/RNase. H Int LTR 1 kb gag LTR pol CCHC Mart 1 Human Mouse 3’ UTR 5’ UTR Human Mart 2 Mouse Human Mart 3 Mouse Human Mart 4 Mouse Human Mart 5 Mouse Human Mart 6 Mouse Human Mouse Mart 7 Mart 8 (x 3) Human (A-C) Mouse (1 -2 A/B) 1. 5 kb Mart 9 Introns Human Mouse The Mart gene family

Southern blot analysis of mouse Mart genes Southern blot analysis of mouse Mart genes

Sushi Mart 1 The Mart family Mart 2 Mart 3 Mart 4 Mart 5 Sushi Mart 1 The Mart family Mart 2 Mart 3 Mart 4 Mart 5 Mart 6 200 aa Mart 7 Mart 8 Mart 9 Pro Gag CCHC RT/RNase. H Pol Int Chr

Mart genes evolve under purifying (negative) selection Gene KA KS KA /KS Mart 1 Mart genes evolve under purifying (negative) selection Gene KA KS KA /KS Mart 1 0. 18 0. 55 0. 33 Mart 2 0. 13 0. 65 0. 20 Mart 3 0. 22 0. 45 0. 49 Mart 4 0. 23 0. 47 0. 49 Mart 5 0. 06 0. 46 0. 13 Mart 6 0. 03 1. 0 0. 03 Mart 7 0. 18 0. 43 0. 42 Mart 8 0. 21 0. 59 0. 36 Mart 9 0. 06 0. 20 0. 30 Comparisons mouse/human

(Molecular) domestication “domesticated” “wild” (Molecular) domestication “domesticated” “wild”

Why are transposable element proteins interesting for the host? TE proteins can - bind Why are transposable element proteins interesting for the host? TE proteins can - bind nucleic acids - copy nucleic acids - break nucleic acids - join nucleic acids - degrade nucleic acids - process proteins - interact with proteins -…

Sushi-like (Gag) Zf Salamander Fugu Human Chimpanzee Gorilla Dog Cow Mouse Rat Macaque Human Sushi-like (Gag) Zf Salamander Fugu Human Chimpanzee Gorilla Dog Cow Mouse Rat Macaque Human A-C Chimpanzee Dog-1 -4 Cow Pig Mouse-1 100 Fugu Frog Trout Mart 9 Mart 1 Dog Mouse Rat Human Chimpanzee Cow Sheep Galago Chimpanzee Human Dog Mart 7 Frog Mouse-2 a/b Rat 87 100 Opossum Human Chimpanzee Baboon Marmoset Cow Pig Bat Dog Cat Shrew 100 96 100 83 69 100 Rat Mouse 100 Mouse Rat Chimpanzee Human Dog Mart 3 Mart 8 s Rat Human Chimpanzee Orangutan Dog Mouse Rat Human Macaque Chimpanzee Rat Dog Mouse Chimpanzee Human Zf Mart 4 Zf Rat Mouse Dog Mouse Mart 2 Zf Mart 6 Mart 5

Evolution of Mart genes and Sushi retrotransposons in the vertebrate lineage Mart Duplication(s)? Domestication(s) Evolution of Mart genes and Sushi retrotransposons in the vertebrate lineage Mart Duplication(s)? Domestication(s) Retrotransposon loss Mart Marsupials vs. placental mammals 170 myr Mammals vs. birds 310 myr Amniotes vs. amphibians 360 myr Tetrapods vs. ray-finned fish 450 myr Mart Loss? - Sushi-like

Possible evolutionary scenarios leading to molecular domestication Possible evolutionary scenarios leading to molecular domestication

Sushi-like (Gag) Salamander Fugu Mart 9 X Mart 1 autosomal imprinted Cow Sheep Galago Sushi-like (Gag) Salamander Fugu Mart 9 X Mart 1 autosomal imprinted Cow Sheep Galago Chimpanzee Human Dog Fugu Frog X X X Mouse-2 a/b Rat 87 100 Opossum Human Chimpanzee Baboon Marmoset Cow Pig Bat Dog Cat Shrew 100 96 100 83 69 100 Rat Mouse 100 Mouse Rat Chimpanzee Human Dog Mart 3 Rat Mart 2 autosomal imprinted Rat Mouse Human Chimpanzee Orangutan Dog Mouse Rat Human Macaque Chimpanzee Rat Dog Mouse Mart 5 Dog Mouse X X Human Chimpanzee Gorilla Mart 8 s Dog Cow Mouse Rat Macaque Human A-C Chimpanzee Dog-1 -4 Cow Pig Mouse-1 100 Trout Dog Mouse Rat Human Chimpanzee Mart 7 Frog Chimpanzee Human Mart 4 X Mart 6 autosomal X

Two autosomal Mart genes, PEG 10 (Mart 2) and PEG 11/Rtl 1 (Mart 1) Two autosomal Mart genes, PEG 10 (Mart 2) and PEG 11/Rtl 1 (Mart 1) are subject to parental imprinting and paternally expressed. Imprinting of both genes is controlled by differentially methylated regions. Two mi. RNA genes are located in Rtl 1, are transcribed in an antisense orientation to Rtl 1 and expressed exclusively from the maternal chromosome (reciprocal imprinting). RNA interference. Since RNA interference and methylation are considered as defence mechanism against mobile DNA, genome imprinting of gag-related genes might be related to retrotransposon silencing.

Expression of Mart genes in mouse adult tissues Expression of Mart genes in mouse adult tissues

Expression of Mart genes during mouse embryogenesis E 14. 5, RT-PCR Expression of Mart genes during mouse embryogenesis E 14. 5, RT-PCR

Function(s) of Mart proteins in mammals? Immunity against retrotransposons Transcription factors Control of cell Function(s) of Mart proteins in mammals? Immunity against retrotransposons Transcription factors Control of cell proliferation and apoptosis Cell adhesion and migration

Paper function mart Paper function mart

Other Gypsy/Ty 3 gag-derived genes in the human genome Campillos et al. 2006 Other Gypsy/Ty 3 gag-derived genes in the human genome Campillos et al. 2006

Another family of gag-derived neogenes in mammals Another family of gag-derived neogenes in mammals

The Ma family of gag-derived neogenes in mammals Wills et al. 2006 The Ma family of gag-derived neogenes in mammals Wills et al. 2006

The Ma family of gag-derived neogenes in mammals Hsa 14 Hsa 8 Hsa. X The Ma family of gag-derived neogenes in mammals Hsa 14 Hsa 8 Hsa. X Paper Ma Hsa. X Wills et al. 2006

Function(s) of Ma proteins in mammals Apoptosis (Ma 4) ? ? Function(s) of Ma proteins in mammals Apoptosis (Ma 4) ? ?

SCAN transcription factors 59 and 40 genes in human and mouse, respectively Regulation of SCAN transcription factors 59 and 40 genes in human and mouse, respectively Regulation of core body temperature, feeding behaviour and obesity (PW 1/Peg 3) Control of lipid metabolism (ZNF 202) Regulation of hippocampal neuronal cholesterol biosynthesis (NRIF) Muscle stem cell behaviour and muscle atrophy (PW 1/Peg 3) Regulation of pluripotency of embryonic stem cells (ZNF 206) Hematopoiesis (MZF 1) Negative regulator of the hypoxia-inducible factor-1 alpha (Zn. F 197) Roles in apoptosis, cell proliferation (several genes) Subject to parental imprinting: Peg 3/Pw 1 (paternally expressed)

Interactome of Gag-derived proteins in mammals Campillos et al. 2006 Interactome of Gag-derived proteins in mammals Campillos et al. 2006

Gypsy/Ty 3 LTR retrotransposons Pro LTR RT/RNase. H pol gag CCHC Int LTR Gypsy/Ty 3 LTR retrotransposons Pro LTR RT/RNase. H pol gag CCHC Int LTR

LRe. O_3 Osvaldo KIAA_1305 TRANSPOSABLE ELEMENTS MGC 80999 DOMESTIC. ELEMENTS GIN 1_Hydre MGC 80999_Chicken LRe. O_3 Osvaldo KIAA_1305 TRANSPOSABLE ELEMENTS MGC 80999 DOMESTIC. ELEMENTS GIN 1_Hydre MGC 80999_Chicken MGC 80999_Zebrafinch MGC 80999_Xenope. L MGC 80999_Xenope. T MGC 80999_Lizard MGC 80999_Stickleback MGC 80999_Takifugu MGC 80999_Tetraodon MGC 80999_Medaka MGC 80999_Zebrafish MGC 80999_Hydre LRe. O 3_Hydre GIN 1_Stickleback GIN 1_Mchenga LRe. O 3_Xenope. T LRe. O 3_Stickleback LRe. O 3_Zebrafish LRe. O 3_Medaka CCHC 26_Cione ZF_Strongylocentrotus LRe. O 3_Ambystoma LRe. O 3_Strongylocentrotus OSJNBa 0019 D 11_Cione OSJNBa 0011 F 23_Strongylocentrot OSJNBa 0059 D 20_Strongylocentrot OSVALDO_Tribolium OSVALDO_Drosophile OSVALDO_Nasonia OSIGBa 0161 P 06_Zebrafish OSJNBa 0086 B 14_Zebrafish KIAA 1305_Cow KIAA 1305_Horse KIAA 1305_Human KIAA 1305_Chimpanzee KIAA 1305_Mouse KIAA 1305_Rat h. CG 40187_Opossum Chicken Cyprinus Xenope Mouse HERV_K Mu. ERV-L KIAA 1466_Human VIH 1 GIN-1 RETROVIRUS Human Chimpanzee Macaca GIN 1_Mouse GIN 1_Rat GIN 1_Cow GIN 1_Pig GIN 1_Horse GIN 1_Opossum GIN 1_Platypus SEC 23_Platypus GIN 1_Lizard GIN 1_Chicken GIN 1_Zebrafinch DOMESTICATED ELEMENTS Domesticated integrase genes

GIN-1 Mammals, birds and reptiles * * On the Z chromosome in birds - GIN-1 Mammals, birds and reptiles * * On the Z chromosome in birds - Conserved HHCC motif - Conserved DDE motif

MGC 80999 Birds, reptiles, amphibians and fish - Conserved HHCC motif - Non-conserved DDE MGC 80999 Birds, reptiles, amphibians and fish - Conserved HHCC motif - Non-conserved DDE motif

Ancient domestication of an integrase gene in vertebrates MGC 80999 Fish Duplication event Amphibians Ancient domestication of an integrase gene in vertebrates MGC 80999 Fish Duplication event Amphibians Reptiles Birds Mammals Molecular domestication event Fish Amphibians Reptiles Birds Mammals GIN-1

LRe. O_3 Osvaldo KIAA_1305 TRANSPOSABLE ELEMENTS MGC 80999 DOMESTIC. ELEMENTS GIN 1_Hydre MGC 80999_Chicken LRe. O_3 Osvaldo KIAA_1305 TRANSPOSABLE ELEMENTS MGC 80999 DOMESTIC. ELEMENTS GIN 1_Hydre MGC 80999_Chicken MGC 80999_Zebrafinch MGC 80999_Xenope. L MGC 80999_Xenope. T MGC 80999_Lizard MGC 80999_Stickleback MGC 80999_Takifugu MGC 80999_Tetraodon MGC 80999_Medaka MGC 80999_Zebrafish MGC 80999_Hydre LRe. O 3_Hydre GIN 1_Stickleback GIN 1_Mchenga LRe. O 3_Xenope. T LRe. O 3_Stickleback LRe. O 3_Zebrafish LRe. O 3_Medaka CCHC 26_Cione ZF_Strongylocentrotus LRe. O 3_Ambystoma LRe. O 3_Strongylocentrotus OSJNBa 0019 D 11_Cione OSJNBa 0011 F 23_Strongylocentrot OSJNBa 0059 D 20_Strongylocentrot OSVALDO_Tribolium OSVALDO_Drosophile OSVALDO_Nasonia OSIGBa 0161 P 06_Zebrafish OSJNBa 0086 B 14_Zebrafish KIAA 1305_Cow KIAA 1305_Horse KIAA 1305_Human KIAA 1305_Chimpanzee KIAA 1305_Mouse KIAA 1305_Rat h. CG 40187_Opossum Chicken Cyprinus Xenope Mouse HERV_K Mu. ERV-L KIAA 1466_Human VIH 1 GIN-1 RETROVIRUS Human Chimpanzee Macaca GIN 1_Mouse GIN 1_Rat GIN 1_Cow GIN 1_Pig GIN 1_Horse GIN 1_Opossum GIN 1_Platypus SEC 23_Platypus GIN 1_Lizard GIN 1_Chicken GIN 1_Zebrafinch DOMESTICATED ELEMENTS Domesticated integrase genes

Domestication/fusion of a retrovirus integrase domain in mammals KIAA 1305 NFATC 4 KIAA 1305 Domestication/fusion of a retrovirus integrase domain in mammals KIAA 1305 NFATC 4 KIAA 1305 CBLN 3 KIAA 0323 N-ter C-ter Similar to Cterminus of KIAA 0323 Retrovirus integrasederived domain

Domesticated transposable element genes in human genome Domesticated transposable element genes in human genome

Putative and confirmed examples of protein-coding neogenes derived from TEs P Gene (family) Protein Putative and confirmed examples of protein-coding neogenes derived from TEs P Gene (family) Protein properties and functions Ancestral gene Ancestral TE Rag 1 Daysleeper Gary Tram Zbed 4 KIAA 0543 P 52 r. IPK Buster 1 -3 Dref Lin-15 B Cenp-b Pdc 2/Rag 3 Jerky-like KIAA 0461 Tigger-derived Metnase P-derived Phsa/Pgga Piggy. Mac Pgbd 1 -4 Pgbd 5 Harb. I 1 Fhy 3, Far 1 Mustang Gin-1 c-integrase Fob 1 p Telomerase Peg 10/Mart 2 Ldoc 1/Mart 7 Other Mart’s Map-1/Ma 1 Other Ma genes Fv 1 Syncytin-2 Syncytin-A/B Other env’s Iris-like nuclease, V(D)J recombination, adaptive immune system DNA binding protein, gene regulation, plant development unknown binding to inhibitor of interferon-induced protein kinase PKR unknown transcription factor, regulation of DNA replication regulator of vulval development DNA binding protein, centromere function transcription factor, regulation of pyruvate utilization neuron m. RNA-binding protein, mutated in epilepsy syndromes unknown DNA integration, radiation resistance, DNA break repair DNA binding protein unknown Elimination of germ-line sequences from macronucleus unknown transcription factors, sensitivity to far-red light unknown replication terminator protein, r. DNA metabolism ribonucleoprotein, reverse transcriptase, telomere replication cell proliferation, transcription factor? , placenta formation inhibition of NF-kappa. B activation, induction of apoptosis unknown Bax-associating protein, induction of apoptosis neuronal autoantigens in paraneoplastic neurological diseases murine leukemia virus restriction membrane glycoprotein, cell fusion, placenta formation unknown defence against viruses? transposase transposase transposase transposase transposase transposase transposase integrase/tpase RT gag gag gag envelope envelope Organisms Transib DNA transposon h. AT DNA transposon h. AT DNA transposon Pogo DNA transposon Tigger/pogo DNA transposon Mariner DNA transposon Piggy. Bac DNA transposon Piggy. Bac DNA transposon Harbinger DNA transposon Mutator DNA transposon Ty 3/gypsy LTR retrotransposon Maverick/LTR element? retroelement Ty 3/gypsy LTR retrotransposon/retrovirus LTR retrotransposon/retrovirus vertebrate retrovirus vertebrate retrovirus Kanga BEL-like retrovirus vertebrates Arabidopsis cereal grasses mammals mammals Drosophila Caenorhabditis eukaryotes yeast mammals human Drosophila mammals, birds Paramecium human bony vertebrates Arabidopsis flowering plants mammals baker's yeast eukaryotes mammals mammals mouse human mouse mammals Drosophila mosquito

Best-studied examples of protein-coding neogenes derived from TEs P Gene Protein properties and functions Best-studied examples of protein-coding neogenes derived from TEs P Gene Protein properties and functions Ancestral TE Organisms Transib DNA transposon h. AT DNA transposon Pogo DNA transposon Piggy. Bac transposon vertebrates Arabidopsis eukaryotes Paramecium Retroelement eukaryotes vertebrate retrovirus mouse vertebrate retrovirus Kanga BEL-like retrovirus human mouse Drosophila Transposase-derived genes Rag 1 Daysleeper Cenp-b Piggy. Mac nuclease, V(D)J recombination, adaptive immune system DNA binding protein, gene regulation, plant development DNA binding protein, centromere, transposon restriction Elimination of germ-line sequences from macronucleus Reverse transcriptase-derived genes (? ) Telomerase ribonucleoprotein, RT, telomere replication Gag-derived genes Fv 1 murine leukemia virus restriction Envelope-derived genes Syncytin-1 Syncytin-2 Syncytin-A/B Iris membrane glycoprotein, cell fusion, placenta formation defence against viruses?

Somatic V(D)J recombination in immunoglobulin genes L: Leader V: Variable C: Constant J: Joint Somatic V(D)J recombination in immunoglobulin genes L: Leader V: Variable C: Constant J: Joint D: Diversity RSSs recombination signal sequences

Reactions catalyzed by the Rag 1/2 recombinase Transposition V(D)J recombination Triangles: recombination signal sequences Reactions catalyzed by the Rag 1/2 recombinase Transposition V(D)J recombination Triangles: recombination signal sequences (RSSs)

Similarities between Rag 1 and RSS with Transib transposons Kapitonov and Jurka 2005 Similarities between Rag 1 and RSS with Transib transposons Kapitonov and Jurka 2005

Kapitonov and Jurka 2005 Kapitonov and Jurka 2005

Best-studied examples of protein-coding neogenes derived from TEs P Gene Protein properties and functions Best-studied examples of protein-coding neogenes derived from TEs P Gene Protein properties and functions Ancestral TE Organisms Transib DNA transposon h. AT DNA transposon Pogo DNA transposon Piggy. Bac transposon vertebrates Arabidopsis eukaryotes Paramecium Retroelement eukaryotes vertebrate retrovirus mouse vertebrate retrovirus Kanga BEL-like retrovirus human mouse Drosophila Transposase-derived genes Rag 1 Daysleeper Cenp-b Piggy. Mac nuclease, V(D)J recombination, adaptive immune system DNA binding protein, gene regulation, plant development DNA binding protein, centromere, transposon restriction Elimination of germ-line sequences from macronucleus Reverse transcriptase-derived genes (? ) Telomerase ribonucleoprotein, RT, telomere replication Gag-derived genes Fv 1 murine leukemia virus restriction Envelope-derived genes Syncytin-1 Syncytin-2 Syncytin-A/B Iris membrane glycoprotein, cell fusion, placenta formation defence against viruses?

Telomerase is a reverse transcriptase Telomerase is a reverse transcriptase

Telomerase is related to retroelement reverse transcriptases Eickbush 1997 Telomerase is related to retroelement reverse transcriptases Eickbush 1997

Best-studied examples of protein-coding neogenes derived from TEs P Gene Protein properties and functions Best-studied examples of protein-coding neogenes derived from TEs P Gene Protein properties and functions Ancestral TE Organisms Transib DNA transposon h. AT DNA transposon Pogo DNA transposon Piggy. Bac transposon vertebrates Arabidopsis eukaryotes Paramecium Retroelement eukaryotes vertebrate retrovirus mouse vertebrate retrovirus Kanga BEL-like retrovirus human mouse Drosophila Transposase-derived genes Rag 1 Daysleeper Cenp-b Piggy. Mac nuclease, V(D)J recombination, adaptive immune system DNA binding protein, gene regulation, plant development DNA binding protein, centromere, transposon restriction Elimination of germ-line sequences from macronucleus Reverse transcriptase-derived genes (? ) Telomerase ribonucleoprotein, RT, telomere replication Gag-derived genes Fv 1 murine leukemia virus restriction Envelope-derived genes Syncytin-1 Syncytin-2 Syncytin-A/B Iris membrane glycoprotein, cell fusion, placenta formation defence against viruses?

Best-studied examples of protein-coding neogenes derived from TEs P Gene Protein properties and functions Best-studied examples of protein-coding neogenes derived from TEs P Gene Protein properties and functions Ancestral TE Organisms Transib DNA transposon h. AT DNA transposon Pogo DNA transposon vertebrates Arabidopsis eukaryotes Retroelement eukaryotes vertebrate retrovirus mouse vertebrate retrovirus Kanga BEL-like retrovirus human mouse Drosophila Transposase-derived genes Rag 1 Daysleeper Cenp-b nuclease, V(D)J recombination, adaptive immune system DNA binding protein, gene regulation, plant development DNA binding protein, centromere, transposon restriction Reverse transcriptase-derived genes (? ) Telomerase ribonucleoprotein, RT, telomere replication Gag-derived genes Fv 1 murine leukemia virus restriction Envelope-derived genes Syncytin-1 Syncytin-2 Syncytin-A/B Iris membrane glycoprotein, cell fusion, placenta formation defence against viruses?

Molecular domestication and disease - Syncytin-1: Oligodendrocytes death and demyelination in multiple sclerosis - Molecular domestication and disease - Syncytin-1: Oligodendrocytes death and demyelination in multiple sclerosis - Rag 1: DNA translocations in lymphatic tumors - Ma‘s: Targets of auto-immune response in paraneoplastic neurological disorders - Peg 10: Cancer

Conclusions Domesticated TE-derived genes are found in major eukaryotic lineages - Animals, Fungi, Plants Conclusions Domesticated TE-derived genes are found in major eukaryotic lineages - Animals, Fungi, Plants Domesticated genes can be derived from different types of retroelements, DNA transposons and viruses Domesticated genes can be derived from different types of genes - Transposase, RT, Gag, integrase, Env, … RNA genes have been also domesticated from TEs - neural gene BC 200 (Alu-derived)

Co-domesticated features? - Epigenetic regulation (imprinting of Mart genes) - Binding sites (Rag 1 Co-domesticated features? - Epigenetic regulation (imprinting of Mart genes) - Binding sites (Rag 1 recombination signal sequences)

Timing of domestication Dog Pig / Sheep / Cow Horse Rabbit Hamster Iris (Env, Timing of domestication Dog Pig / Sheep / Cow Horse Rabbit Hamster Iris (Env, insects) Mart (Gag, mammals) P-derived (transposase, tetrapods) Rag 1 (transposase, vertebrates) Telomerase (RT, eukaryotes) Minimal date (years ago) 17. 000 10. 000 4. 000 500 80 25. 000 180. 000 300. 000 500. 000 1. 000

Transposable elements are a major source of regulatory and coding sequences for genetic innovation Transposable elements are a major source of regulatory and coding sequences for genetic innovation

Equipe “Génomique Evolutive des Vertébrés“ Institut de Génomique Fonctionnelle de Lyon CNRS/INRA/UCBL/ENSL Domitille Chalopin Equipe “Génomique Evolutive des Vertébrés“ Institut de Génomique Fonctionnelle de Lyon CNRS/INRA/UCBL/ENSL Domitille Chalopin Astrid Böhne Frédéric Brunet Christina Schultheis Amandine Darras Delphine Galiana-Arnoux Jean-Nicolas Volff http: //igfl. ens-lyon. fr/les-equipes/equipe-9

Collaborations Manfred Schartl (University of Würzburg, Germany) Manfred Gessler (University of Würzburg, Germany) Indrajit Collaborations Manfred Schartl (University of Würzburg, Germany) Manfred Gessler (University of Würzburg, Germany) Indrajit Nanda, Michael Schmid (University of Würzburg, Germany) Cécile Fischer, Laurence Bouneau, Sylvie Samain, Jean Weissenbach (Genoscope, Evry, France) Catherine Ozouf-Costaz, Agnés Dettai (Muséum National d’Histoire Naturelle, Paris, France) Daniel Chourrout (SARS Centre, Bergen, Norway) Christoph Winkler (University of Singapore) Yann Guigen (INRA Rennes) Carine Genet (INRA Jouy) Christophe Terzian (Lyon)