LINE s & SINE s

1. LINEs &SINEs

2. The genome of most eukaryotes contains highly-repetitive interspersed sequences: (1) short-interspersed repetitive elements (SINEs) (2) long-interspersed repetitive elements (LINEs).

3. ~1/2 of the human genome consists of interspersed repetitive sequences.

6. Original definitions: interspersed repeats

7. Current definitions: LINEs = Active or degenerate descendants of transposable elements. SINEs = Non-autonomous transposable elements (lacking the ability to mediate their own transposition) and their degenerate descendents.

9. The reverse transcriptase has LINE specificity, i.e., a reverse transcriptase from one LINE will only recognize the 3’ end of that LINE, and will be less efficient at recognizing and reverse transcribing other LINEs.

10. SINEs are retrosequences that range in length from 75 to 500 bp. SINEs do not possess any reading frame. Thus, their retroposition must be aided by other genetic elements.

11. Primate Alu + Rodent B1 All others SINE 7SL-RNAderived tRNA-derived

12. Alu elements • Length = ~300 bp • Repetitive: > 1,000,000 times in the human genome • Constitute >10% of the human genome • Found mostly in intergenic regions and introns • Propagate in the genome through retroposition (RNA intermediates).

14. Evolution of Alu elements (I)

15. Evolution of Alu elements (II) FAM FLAM FRAM

17. Master-gene model for Alu proliferation in the genome Progeny undergoes multiple independent mutations Replicatively incompetent progeny Master gene A Mutation renders A non-functional & creates new master gene B Mutation renders B non-functional & creates new master gene C

19. Alu elements can be divided into subfamilies The subfamilies are distinguished by ~16 diagnostic positions.

20. diagnostic positions

21. Alu elements are found only in primates.  All the millions of Alu elements have accumulated in a mere ~65 million years.

22. Alu elements can be sorted into distinct families according to shared patterns of variation.  At any given point in time, only one or several Alu “master copies” are capable of transposing.

23. Early in primate evolution, Alu transposition rate was approximately one new jump in every live birth. Today, it is about one new jump in every 200 live births.

24. PV92, a human-specific Alu insertion on chromosome 16 There are two alleles: with (+) or without (–) the Alu transposable element. There are three genotypes (++, + –, ––). The + and – alleles can be separated by size using gel electrophoresis.

25. tRNA derived SINEs

26. a tRNA-derived SINE twin SINE 500 per haploid genome Culex pipiens

27. Norihiro Okada et al.

28. Bombyx mori

30. 3 predictions: 1. Where there’s a SINE, there’s a LINE! 2. Once a LINE partner becomes inactive, the SINE partner will lose its ability to retrotranspose. 3.A LINE partner should have a longer evolutionary history and, hence, a broader phylogenetic distribution than its SINE partner.

32. GENETIC AND EVOLUTIONARY EFFECTS OF TRANSPOSITION 1. Duplicative transposition increases genome size. Lily Edible frog Sunflower

33. 2. Bacterial transposons often carry genes that confer antibiotic or other forms of resistance. Plasmids can carry such transposons from cell to cell, so that resistance can spread throughout a population or an ecosystem.

35. A figure used by Barbara McClintock at her Nobel Prize (1983) Lecture

36. 3. Gene expression may be altered by the presence of a transposable element. a. An insertion may obliterate the reading frame (phenotypic effects). b. A transposable element may contain regulatory elements (effects on transcription of nearby genes). c. Transposable elements may contain splice sites (effects on RNA processing even if the element is in an intron).

38. Caused by the insertion of a transposable element.

39. Transposable elements in Antirrhinum majus

40. nivea recurrens cinnamic acid chalcone eriodictyol dihydroquercetin cyanidin

41. nivea incolorata pallida cinnamic acid chalcone eriodictyol dihydroquercetin cyanidin

43. rugosus

46. 4. Transposable elements promote gross genomic rearrangements a. directly (moving a DNA sequence from one genomic location to another). b. indirectly (as a result of transposition, two sequences become similar to one another so that unequal crossing-over between them is possible).

49. An unequal crossing-over event facilitated by the presence of multiple Alu sequences in the introns flanking exon 5 of the low-density-lipoprotein-receptor gene, has given rise to a mutant gene lacking exon 5 (FH-626a). Patients homozygous for this deletions have hypercholesterolemia.

50. 5. Insertion of transposable elements into some members of a multigene family but not others will reduce the rate and limit the extent of gene conversion between the members of the family and, therefore, increase the rate of divergence between duplicate genes.