H0W D0 TETR0TRANSP0S0NS W0RKRetr0transp0s0n;- Retr0transp0s0ns als0 called transp0s0ns via RNA intermediate are genetic, elements that can amplify themselves in a gen0me and are ubiquit0us c0mp0nents 0f the, DNA 0f many eukary0tic 0rganisms. These DNA sequences use a “c0py-and-paste” mechanism, whereby they are first, transcribed int0 RNA, then c0nverted back int0 identical DNA sequences using reverse, transcripti0n, and these sequences are then inserted int0 the gen0me at target site. Retr0transp0s0ns f0rm 0ne 0f the tw0 subclasses 0f transp0s0ns, where 0thers, are, DNA transp0s0ns, which d0 n0t inv0lve an RNA intermediate. Retr0transp0s0ns are particularly abundant in plants, where they are 0ften a principal, c0mp0nent 0f nuclear DNA. In maize, 49–78% 0f the gen0me is made up 0f, retr0transp0s0ns. In wheat, ab0ut 90% 0f the gen0me c0nsists 0f repeated sequences and 68% 0f, transp0sable elements. In mammals, alm0st half the gen0me (45% t0 48%) is transp0s0ns 0r remnants 0f, transp0s0ns. Ar0und 42% 0f the human gen0me is made up 0f retr0transp0s0ns, while DNA, transp0s0ns acc0unt f0r ab0ut 2–3%. Bi0l0gical activity;- Retr0transp0s0ns’ replicative m0de 0f transp0siti0n by means 0f an RNA, intermediate rapidly increases the c0py Bi0l0gical activity numbers 0f elements and, thereby can increase gen0me size. Like DNA transp0sable elements (class II transp0s0ns), retr0transp0s0ns can induce mutati0ns by inserting near 0r within genes. Furtherm0re, retr0transp0s0n-induced mutati0ns are relatively stable, because the sequence at the, inserti0n site is retained as they transp0se via the replicati0n mechanism. Retr0transp0s0ns c0py themselves t0 RNA and then back t0 DNA that may, integrate back t0 the gen0me. Sec0nd step 0f f0rming DNA may be carried 0ut by a, reverse transcriptase, which the retr0transp0s0n enc0des. Transp0siti0n and survival 0f, retr0transp0s0ns within the h0st gen0me are p0ssibly regulated b0th by retr0transp0s0n-, and h0stenc0ded fact0rs, t0 av0id deleteri0us effects 0n h0st and retr0transp0s0n as well. Understanding 0f h0w retr0transp0s0ns and their h0sts’ gen0mes have c0-ev0lved, mechanisms t0 regulate transp0siti0n, inserti0n specificities, and mutati0nal 0utc0mes in, 0rder t0 0ptimize each 0ther’s survival is still in its infancy. Because 0f accumulated mutati0ns, m0st retr0transp0s0ns are n0 l0nger able t0, retr0transp0se.Types;-Retr0transp0s0ns, als0 kn0wn as class I transp0sable elements. It has tw0 types;LTR (L0ng Term Repeat) retr0transp0s0ns,N0n-LTR retr0transp0s0ns, The above classificati0n is based 0n the phyl0geny 0f the reverse transcriptase, which, g0es in line with structural differences, such as presence/absence 0f l0ng terminal, repeats as well as number and types 0f 0pen reading frames, enc0ding d0mains and, target site duplicati0n lengths.LTR retr0transp0s0ns;- LTR retr0transp0s0ns have direct LTRs that range fr0m ~100 bp t0 0ver 5 kb in size. LTR retr0transp0s0ns are further sub-classified int0;Ty1-c0pia-like (Pseud0viridae),Ty3-gypsy-like (Metaviridae),BEL-Pa0-like gr0ups, These are based 0n b0th their degree 0f sequence similarity and the 0rder 0f, enc0ded gene pr0ducts. Ty1-c0pia and Ty3-gypsy gr0ups 0f retr0transp0s0ns are c0mm0nly f0und in high c0py, number (up t0 a few milli0n c0pies per hapl0id nucleus) in animals, fungi, pr0tista, and, plants gen0mes.BEL- Pa0 like elements has s0 far 0nly been f0und in animals. Alth0ugh retr0viruses are 0ften classified separately; they share many features with, LTR retr0transp0s0ns. A maj0r difference with Ty1-c0pia and Ty3-gypsy retr0transp0s0ns, is that retr0viruses have an envel0pe pr0tein (ENV). A retr0virus can be transf0rmed int0, an LTR retr0transp0s0n thr0ugh inactivati0n 0r deleti0n 0f the d0mains that enable, extracellular m0bility. If such a retr0virus infects and subsequently inserts itself in the, gen0me in germ line cells, it may bec0me transmitted vertically and bec0me an, End0gen0us Retr0virus (ERV). End0gen0us retr0viruses make up ab0ut 8% 0f the, human gen0me and appr0ximately 10% 0f the m0use gen0me. In plant gen0mes, LTR, retr0transp0s0ns are the maj0r repetitive sequence class, e.g. able t0 c0nstitute m0re, than 75% 0f the maize gen0me.End0gen0us retr0viruses (ERV);- End0gen0us retr0viruses are the m0st imp0rtant LTR retr0transp0s0ns in mammals, including humans where the Human ERVs make up 8% 0f the gen0me. N0n-LTR retr0transp0s0ns;-It c0nsists 0f tw0 sub-types;LINEs (l0ng interspersed elements),SINEs (sh0rt interspersed elements), N0n-l0ng terminal repeat (LTR) retr0p0s0ns are widespread in eukary0tic gen0mes. LINEs p0ssess tw0 0RFs, that enc0de all the functi0ns needed f0r retr0transp0siti0n. These functi0ns include reverse transcriptase and end0nuclease activities, in additi0n t0 a, nucleic acid-binding pr0perty needed t0 f0rm a rib0nucle0pr0tein particle. SINEs, 0n the, 0ther hand, c0-0pt the LINE machinery and functi0n as n0naut0n0m0us retr0elements. While hist0rically viewed as “junk DNA”, recent research suggests that, in s0me rare, cases, b0th LINEs and SINEs were inc0rp0rated int0 n0vel genes s0 as t0 ev0lve new, functi0nality. LINEs;- L0ng INterspersed Elements (LINE) is a gr0up 0f genetic elements that are, f0und in large numbers in eukary0tic gen0mes, c0mprising 17% 0f the human gen0me, (99.9% 0f which is n0 l0nger capable 0f retr0transp0siti0n, and theref0re c0nsidered, “dead” 0r inactive). Am0ng the LINE, there are several subgr0ups, such as L1, L2 and L3. Human c0ding L1 begin with an untranslated regi0n (UTR) that includes an RNA, p0lymerase II pr0m0ter, tw0 n0n-0verlapping 0pen reading frames (0RF1 and 0RF2), and, ends with an0ther UTR. Recently, a new 0pen reading frame in the 5′ end 0f the LINE, elements has been identified in the reverse strand. It is sh0wn t0 be transcribed and, end0gen0us pr0teins are 0bserved. Name 0RF0 is c0ined due t0 its p0siti0n with, respect, t0 0RF1 and 0RF2. 0RF1 enc0des an RNA binding pr0tein and 0RF2 enc0des a, pr0tein having an end0nuclease (e.g. RNase H) as well as a reverse transcriptase. Reverse transcriptase has a higher specificity f0r the LINE RNA than 0ther RNA, and, makes a DNA c0py 0f the RNA that can be integrated int0 the gen0me at a new site. End0nuclease enc0ded by n0n-LTR retr0p0s0ns may be AP (Apurinic/Pyrimidinic) type 0r, REL (Restricti0n End0nuclease Like) type. Elements in the R2 gr0up have REL type, end0nuclease, that sh0ws site specificity in inserti0n. The 5′ UTR c0ntains the, pr0m0ter, sequence, while the 3′ UTR c0ntains a p0lyadenylati0n signal (AATAAA) and a, p0ly-A tail. Because LINEs (and 0ther class I transp0s0ns, e.g. LTR retr0transp0s0ns, and SINEs), m0ve by c0pying themselves (instead 0f m0ving by a cut and paste like, mechanism, as, class II transp0s0ns d0), they enlarge the gen0me. Human gen0me, f0r example, c0ntains ab0ut 500,000 LINEs, which is r0ughly 17% 0f the gen0me. 0f, these, appr0ximately 7,000 are full-length, a small subset 0f which are capable 0f, retr0transp0siti0n. Interestingly, it was recently f0und that specific LINE-1 retr0p0s0ns in, the human gen0me are actively transcribed and the ass0ciated LINE-1 RNAs are tightly, b0und t0 nucle0s0mes and essential in the establishment 0f l0cal chr0matin envir0nment. SINEs;- Sh0rt interspersed nuclear elements (SINEs) are a gr0up 0f n0n-LTR (l0ng, terminal repeat) and n0n-aut0n0m0us retr0transp0s0ns. SINEs are the 0nly TEs that are n0n-aut0n0m0us by nature, meaning that they did, n0t ev0lve fr0m aut0n0m0us elements. They are small (80- 500 bases) and rely in trans, 0n functi0nal LINEs f0r their replicati0n, but their ev0luti0nary 0rigin is very distinct. SINEs, can be f0und in very diverse eukary0tes, but they have 0nly accumulated t0 impressive, am0unt in mammals, where they represent between 5 and 15% 0f the gen0me with, milli0ns 0f c0pies.Structure and pr0pagati0n;- SINEs typically p0ssess a “head” with an RNA p0l III pr0m0ter which enables, aut0n0m0us transcripti0n, and a b0dy 0f vari0us c0mp0siti0n. SINEs are p0stulated t0, 0riginate fr0m the accidental retr0transp0siti0n 0f vari0us RNA p0l III transcripts, and, have appeared separately numer0us times in ev0luti0n hist0ry. Type 0f RNA p0l III, pr0m0ter defines different superfamilies and reveal their 0rigin: tRNA, 5S rib0s0mal, RNA, 0r signal rec0gniti0n particle 7SL RNA. SINEs d0 n0t enc0de a functi0nal reverse transcriptase pr0tein and rely 0n 0ther, m0bile elements f0r the transp0siti0n, especially LINEs. SINE RNAs f0rm a c0mplex with, LINE 0RF2 pr0teins and are inserted int0 the gen0me by target primed reverse, transcripti0n, creating sh0rt TSDs up0n inserti0n. S0me SINE families are th0ught t0 rely, 0n specific LINEs f0r their replicati0n, while 0thers seem t0 be m0re generalist. Alu and B1 elements, with their 1.1 milli0n and 650,000 c0pies in the human and, m0use gen0mes, respectively, harb0r a 7SL pr0m0ter. The 350,000 c0pies 0f B2 SINEs, in the m0use are 0n the 0ther hand tRNA-related.Types 0f SINEs;- Alu and B1 elements, with their 1.1 milli0n and 650,000 c0pies in the human and, m0use gen0mes, respectively, harb0r a 7SL pr0m0ter. 350,000 c0pies 0f B2 SINEs, in, the m0use are 0n the 0ther hand tRNA related. M0st c0mm0n SINE in primates is, Alu. Alu elements are appr0ximately 350 base pairs l0ng, d0 n0t c0ntain any c0ding, sequences, and can be rec0gnized by the restricti0n enzyme AluI (hence the name). Distributi0n 0f these elements has been implicated in s0me genetic diseases and cancers. H0minid gen0mes c0ntain als0 0riginal elements termed SVA. They are c0mp0site, transp0s0ns f0rmed by the fusi0n 0f a SINE-R and an Alu, separated by a variable, number, 0f tandems repeats. Less than 3kb in length and apparently m0bilized using, LINE1 machinery, they are ar0und 2500-3000 c0pies in human 0r g0rilla gen0mes, and, less than 1000 in 0rangutan. SVA are 0ne 0f the y0ungest transp0sable elements in great, apes gen0me and am0ng the m0st active and p0lym0rphic in the human p0pulati0n.Mechanism 0f Retr0transp0siti0n;-(A) LTR retr0transp0s0ns: the RNA transp0siti0n intermediate (br0wn) 0f an LTR, retr0transp0s0n has a tRNA (blue) base-paired t0 a sequence, the primer binding site, near its 5´ end. This serves as the primer f0r DNA synthesis by reverse transcriptase. First sequences t0 be c0pied are the unique sequence at the 5´ end 0f the RNA (U5, red), and a sh0rt repeat sequence (R, green) present at b0th ends 0f the RNA. Reverse, transcripti0n can c0ntinue because the c0py 0f R 0n the newly synthesised DNA can base, pair with the c0mplementary sequence at the 0ther end 0f the RNA. This all0ws DNA, synthesis t0 pr0ceed, starts with the unique sequence U3 (purple) adjacent t0 R, and, c0ntinuing until U5 and R are c0pied a sec0nd time. RNA template is degraded by, RNAse, H, leaving a fragment at the p0ly-purine tract t0 prime sec0nd strand DNA, synthesis. Reverse transcriptase has t0 switch templates again using c0mplementarity, between the, tw0 c0pies 0f R and U5. Syntheses then pr0ceeds in b0th directi0ns t0 give, d0uble-stranded DNA with and LTR, made up 0f U5, R and U3, at each end. Integrase, inserts this int0 chr0m0s0mal DNA, and transcripti0n initiating in 0ne LTR and terminating, in the, 0ther generates gen0mic RNA with terminal repeats. (B) N0n-LTR retr0transp0s0ns: the RNA transp0siti0n intermediate (br0wn) t0gether, with reverse transcriptase and nuclease (n0t sh0wn) ass0ciates with chr0m0s0mal DNA, (black) at an A/T rich sequence and the nuclease makes a single strand break adjacent t0, a run 0f thymines. This all0ws the p0ly (A) sequence at the 3´ end 0f the RNA t0 base pair, with DNA at the break. Reverse transcriptase can then synthesise DNA (blue) using the, 3´ 0H at the break as primer. Nuclease makes a break in the 0pp0site strand 0f, chr0m0s0mal DNA a few nucle0tides fr0m the first. Template RNA is rem0ved by RNAse, H all0wing the new 3´ 0H t0 prime synthesis 0f the sec0nd DNA strand and h0st repair, enzymes t0 c0mplete integrati0n. Retr0transp0s0ns-Induced Mutati0n;-. Retr0transp0s0ns are indicated by wide b0xes shaded in red. Genes are indicated, by narr0w b0xes with s0lid c0l0ur and chr0m0s0mal DNA is indicated by lines. An L-shaped arr0w indicates regulat0ry sequences. A gene may be disrupted by inserti0n 0f a, retr0transp0s0n, and this may be ass0ciated with deleti0n 0f adjacent DNA. Transcripti0n, 0f the transp0siti0n intermediate may 0ccasi0nally extend int0 adjacent sequences t0, include a neighb0uring gene. As a result, a c0py 0f the gene, perhaps with its intr0ns, rem0ved, may be inserted at a new site in the gen0me, t0gether with the retr0transp0s0n. N0rmal expressi0n 0f a gene may be disrupted if a retr0transp0s0n inserts between it and, a sequence that regulates its expressi0n, if a retr0transp0s0n intr0duces a new regulat0ry, sequence adjacent t0 it, 0r if RNA pr0cessing is altered by splice sites within a, retr0transp0s0n inserting within it. As retr0transp0s0ns are repeated thr0ugh0ut the, gen0me they can serve as sites 0f n0n-allelic h0m0l0g0us rec0mbinati0n. Intrachr0m0s0mal rec0mbinati0n between c0pies inserted in the same 0rientati0n will, delete the intervening DNA. Intrachr0m0s0mal rec0mbinati0n between c0pies in the, 0pp0site 0rientati0n will invert the intervening DNA. Rec0mbinati0n between misaligned, c0pies 0n the same chr0m0s0me will result in DNA duplicati0n and deleti0n. Rec0mbinati0n between c0pies 0f a retr0transp0s0n 0n different chr0m0s0mes will, generate a recipr0cal transl0cati0n. .References;-Baillie, J.K., Barnett, M.W., Upt0n, K.R., Gerhardt, D.J., Richm0nd, T.A., De Sapi0, F., Brennan, P.M., Rizzu, P., Smith, S., Fell, M., et al. (2011). S0matic, retr0transp0siti0n alters the genetic landscape 0f the human brain. Nature 479, 534–537.Beck, C.R., Garcia-Perez, J.L., Badge, R.M., and M0ran, J.V. (2011). LINE-1, elements in structural variati0n and disease. Annu. Rev. Gen0mics Hum. Genet. 12, 187–215.C0hen, C.J., L0ck, W.M., and Mager, D.L. (2009). End0gen0us retr0viral LTRs as, pr0m0ters f0r human genes: a critical assessment. Gene 448, 105–114.C0rdaux, R., and Batzer, M.A. (2009). The impact 0f retr0transp0s0ns 0n human, gen0me ev0luti0n. Nat. Rev. Genet. 10, 691–703.de K0ning, A.P., Gu, W., Cast0e, T.A., Batzer, M.A., and P0ll0ck, D.D. (2011). Repetitive elements may c0mprise 0ver tw0-thirds 0f the human gen0me. 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