The evolution of selfishness HW#5: FASTA sequence Function

Human genome

Klug & Cummings 2000

Transposable elements in bacteria- Insertion Sequence (IS)

Transposable elements in bacteria- Insertion Sequence (IS) replicative transposition Shapiro, J Molecular model for the transposition and replication of bacteriophage Mu and other transposable elements. Proc. Natl. Acad. Sci. USA 76:

Repetitive DNA- Transposable elements

Transposable elements- transposition machinery Retrotransposition

Virus vs. Retrotransposon

Transposition machinery Henry S Levin 2011

A, The overall composition of species-specific insertions in humans and chimpanzees. Note that 97.2% of all insertions in humans and 95.6% of all insertions in chimpanzees are Alu, L1, and SVA insertions. B, The distributions of Alu and L1 subfamilies for humans. C, The distributions of Alu and L1 subfamilies for chimpanzees Mills et al Classes of species specific transposons in human and chimpanzees

Mills et al. 2007

How can we control them?

Why do we need them?

Non-LTR retroelement (Class I) Comprises 17% of the human genome. ORF1 encodes 40KD nucleic acid binding protein. ORF2 encodes for both reverse transcriptase (RT) and endonuclease (EN). Retrotransposon- L1

Coufal et al (hCNS-SCns) human fetal brain stem cells L1 retrotransposition in hCNS-SCns

1,243bp product contains the intron 342bp product indicates intron loss and retrotransposition 1 weight standards 2 hCNS-SCns transfected with JM111/L1RP 3-5, three hCNS-SCns lines transfected with L1RP 6-7, primary astrocytes and fibroblasts transfected with L1RP 8, positive control 9, water Coufal et al PCR of genomic DNA

Coufal et al Time course of L1 retrotransposition

EGFP-positive hCNS-SCns also could be differentiated to cells of both the neuronal and glial lineages EGFP-positive cells can differentiate to neurons EGFP-positive cells can differentiate into glia EGFP-positive cells express Nestin and Sox2 Coufal et al. 2010

L1 retrotransposition in hESC-derived NPCs and some HUES6-derived NPCs are functional L1 5′ UTR is induced upon differentiation. voltage step depolarizations Suprathreshold responses to somatic current injections Spontaneous action potentials Coufal et al hESC human embryonic stem cell

Methylation analysis for the endogenous human L1 5′ UTR Coufal et al. 2010

Methylation analysis for the endogenous human L1 5′ UTR

Multiplex quantitative PCR analyses of L1 copy number in human tissues Coufal et al. 2010

Multiplex quantitative PCR analyses of L1 copy number in human tissues Coufal et al. 2010

So, why do we need them?

A group of terms having similar biological meaning due to sharing similar gene members Clustering options and stringency Every term in the annotation cluster Related term Genes involved in individual term

Genes in the gene group Highly common of annotation Difference of annotation

All genes Genes in one gene term Genes in my list ? P-value