Renealmia occidentalis (Swartz) Sweet

The.Human.Genome.Project,.which.sequenced.the.entire.genome,.revealed.that.genes.are.only.the.

“tip.of.the.iceberg.”.The.vast.majority.of.the.genome.is.not.made.up.of.genes.at.all.[Ridley.1999].

but.by.other.material.known.as.introns.(non–protein-coding.DNA.sequences.that.occur.in.packets.

between. and. among. the. genes).. The. “average”. protein. contains. about. 333. AAs,. so. 1,000. DNA.

bases.are.required.to.code.each.protein,.or.a.total.of.about.1,000.×.30,000.genes.=.3.×.10⁷.bases.are.

required..However,.it.is.estimated.that.the.entire.human.genome.has.a.total.of.about 3.gigabases.(3.1.

×.10⁹),.so.it.appears.that.only.about.1%.of.the.human.genome.is.protein-coding.genes;.about.99%.

table .

amino acid coding by nucleotides (codons)

u c a g

U Phenylalanine Serine Tyrosine Cysteine U C

Leucine Stop Stop A

Stop Tryptophan G

C Leucine Proline Histidine Arginine U C

Glutamine A

G A Isoleucine Threonine Asparagine Serine U C

Lysine Arginine A

Methionine G

G Valine Alanine Aspartic.acid Glycine U C

Glutamic.acid A

G

is.non–protein-coding.DNA,.either.codes.RNAs.or.has.poorly.understood.or.unknown.regulatory.

functions,.or.even.no.function.at.all..Scientists.once.referred.to.introns.as.“junk.DNA,”.but.recent.

discoveries.have.indicated.that.this.is.far.from.the.case.[Gibbs.2003].

Introns.may.also.be.defined.as.sections.of.DNA.that.will.be.spliced.out.after.transcription.but.

before.the.mRNA.is.used..Introns.are.common.in.all.eukaryotic.RNAs.but.are.rare.in.prokaryotes.

[Lynch.2002]..In.contrast.to.introns.are.exons,.the.regions.of.a.gene.that.remain.in.spliced.(edited).

mRNA.[McClean.1998]..They.code.for.proteins.[Traut.1988].

Any.intron.bases.lying.within.a.mammalian.gene.are.transcribed.into.the.premessenger RNA.

(pmRNA).for.the.gene.and.then.are.“edited”.out.of.the.gene.sequence.in.the.pmRNA.before.protein.

synthesis.occurs..The.editing.is.done.in.a.complex.eight-step.process.by.a.set.of.five.nuclear.“care-taker”.RNA.molecules.known.collectively.as.a.spliceosome. The.spliceosome.is.composed.of.five.

subunits.called.small nuclear ribonuclear proteins.(snRNP).[MCB.411.2000]..This.is.a.wonderful.

and.indispensable.molecular.machine.as.far.as.proteins.are.concerned,.because.our.genome.is.99%.

irrelevant.in.terms.of.polypeptide.(protein).coding..(The.details.of.how.the.spliceosome.works.are.

beyond.the.scope.of.this.text.)

With. what. is. now. evident. as. short-sightedness. and. hubris,. scientists. once. referred. to. intron.

DNA.as.“junk”.DNA.[Ohno.1972]..It.now.turns.out.that.introns.can.contain.cis-regulatory elements.

(base.sequences).that.determine.which.(and.when).master.control.genes.are.activated,.thus.provid-ing. a. clue. to. how. embryonic. development. takes. place.. As. discussed. throughout. this. text,. many.

introns.have.other.epigenetic.functions..Introns.can.also.contain.RNA.coding.sequences.

table .

amino acids coded by Dna codons (Replace t with u for mRna codons)

aa name abbreviation one-letter abbreviation Dna codons for each aa

Tryptophan Trp W TGG

Methionine Met M ATG*

Aspartic.acid Asp D GAC, GAT

Glutamic.acid Glu E GAA, GAG

Cysteine Cys C TGC, TGT

Histidine His H CAC, CAT

Asparagine Asp N AAC, AAT

Lysine Lys K AAA, AAG

Phenylalanine Phe F TTC, TTT

Glutamine Gln Q CAA, CAG

Tyrosine Tyr Y TAC, TAT

Isoleucine Ile I ATA, ATC, ATT

Alanine Ala A GCA, GCC, GCG, GCT

Glycine Gly G GGA, GGC, GGG, GGT

Proline Pro P CCA, CCC, CCG, CCT

Arginine Arg R CGA, CGC, CGG, CGT

Threonine Thy T ACA, ACC, ACG, AGT

Valine Val V GTA, GTC, GTG, GTT

Leucine Leu L TTA, TTG, CTA, CTC, CTG, CTT

Serine Ser. S TCA, TCC, TCG, TCT, AGC, AGT

Start ATG*

Stop,.release TAA, TAG, TGA

The Basis of Genetic Inheritance 

It. is. our. opinion. that. about. 99%. of. our. DNA. is. not. noise. or. junk,. just. because. it. does. not.

directly.code.proteins..One.wonder.of.life.lies.in.its.many.biochemical.regulatory.mechanisms..The.

elaboration.of.the.cis-regulatory DNA base sequences.in.introns.promises.to.be.a.major.challenge.

in.genomics.in.the.next.decade..Evidently,.the.Human.Genome.Project.will.continue.for.some.time.

as.scientists.clarify.the.complex.molecular.mechanisms.of.genetic.regulation.and.developmental.

timing.associated.with.introns.

There.are.many.hypotheses.of.how.introns.arose.and.why.they.persist.in.the.eukaryotic.genome..

For.example,.it.is.widely.believed.that.introns.once.served.as.spacers.between.the.sections.of.DNA.

that.coded.for.specific,.comparatively.simple.proteins..During.the.evolution.of.complex.proteins,.

regions.of.the.genetic.code.may.have.been.shuffled.to.generate.new.sequences.[Bidwai.1999].

It.is.also.believed.that.many.introns.were.originally.ancient.genes.that.have.since.lost.their.pro-tein-coding.ability.and.their.original.function.[Koonin.2006],.although.they.can.now.retain.certain.

epigenetic.functions.[Fedorov.&.Fedorova.2004].

A.known.source.of.introns.is.retrotransposons, which.constitute.up.to.half.of.the.human.genome.

[Deininger.&.Batzer.2002]..About.8%.of.the.human.genome.is.made.up.of.a.type.of.retrotransposon.

known.as.Human Endogenous Retroviruses.(HERVs).[Polavarapu.et.al..2006].

Transposons and retrotransposons:. An. important. example. of. an. intron. is. the. transposon,. a.

class. of. genetic. “parasite”. that. includes. retroviruses. [Economist. 2005].. Transposons. are. mobile.

genetic. elements. that. can. move. from. chromosome. to. chromosome.. When. they. skip. the. normal.

genetic.flow.of.information.through.transcription.and.use.reverse.transcriptase.to.copy.and.splice.

themselves.directly.into.DNA,.they.are.known.as.retrotransposons.[Salk.Institute.2005].

The.most.common.form.of.retrotransposon.is.called.LINE-1..This.is.a.“paragraph”.of.DNA,.

between.1,000.and.6,000.bases.long,.that.includes.the.code.for.reverse.transcriptase..There.are.as.

many.as.100,000.unique.copies.of.LINE-1.sequences.in.each.copy.of.your.DNA,.and.many.of.them.

are.repeated.[Salk.Institute.2005].

Recent.research.shows.that.transposons.may.be.a.“major.creative.force.in.the.evolution.of.mam-malian.gene.regulation”.[Mikkelsen.et.al..2007]..Over.99%.of.the.genes.of.Monodelphus domestica.

(a.small.South.American.opossum).are.also.found.in.humans.[NIH.2007]..Opossums.belong.to.the.

infraclass.Metatheria,.the.marsupial.branch.of.the.mammalian.class,.in.contrast.with.Eutheria,.the.

placental.mammals..Eutheria.and.Metatheria.split.between.125.and.144.MYA.[Ogburn.&.Brogdon.

2004]..The.comparison.of.opossum.and.eutherian.genes.shows.that.“true.innovation.in.protein-coding.genes.seems.to.be.relatively.rare”.[Mikkelsen.et.al..2007]..In.other.words,.the.differences.

between.opossums.and.humans,.from.the.point.at.which.they.diverged.from.the.common.ancestors,.

are.due.almost.entirely.to.noncoding.regions,.or.introns..Specifically,.the.differences.are.due.to.the.

activity.of.transposons.[Mikkelsen.et.al..2007].

Because.they.move.around.the.genome.so.much,.retrotransposons.often.“jump”.into.the.middle.

of.normal.genes,.damaging.or.mutating.them..This.sounds.serious,.but.the.good.news.is.that.ret-rotransposons.are.naturally.suppressed.in.the.human.genome.through.methylation..This.may,.in.

fact,.be.one.reason.that.methylation.evolved.[Ridley.1999]..Some.researchers.believe.that.transpo-sons.played.a.key.role.in.the.evolution.of.complexity.in.eukaryotes.[Bowen.&.Jordan.2002].

Retroviruses.transcribe.RNA.into.DNA.(the.inverse.of.the.“normal”.process).using.a.spe-cial.enzyme.called.reverse.transcriptase..Interestingly,.the.gene.for.reverse transcriptase.is.the.

most.common.gene.in.the.human.genome,.even.though.it.serves.no.function.in.the.human.body..

Reverse.transcriptase.was.“planted”.in.human.DNA.by.retroviruses.as.a.way.to.enter.the.genome..

It.is.as.if.a.computer.hacker.planted.a.“back.door”.that.would.allow.unauthorized.entry.to.another.

person’s.computer.

The.resulting.DNA.is.inserted.into.a.host.cell’s.DNA.using.an.enzyme.called.integrase.and.

is.reproduced.along.with.the.rest.of.the.cell’s.genome..The.viral.DNA.in.the.daughter.cell.then.

makes.an.RNA.copy.of.itself.that.is.covered.in.a.protein.shell.and.leaves.the.cell.to.infect.new.cells.

[Columbia.University.Press.2003].

Some.retroviruses.can.jump.between.species..These.are.known.as.exogenous.retroviruses..Ret-roviruses,.especially.exogenous.retroviruses,.sometimes.destroy.the.cells.whose.DNA.they.alter,.as.

with.HIV,.the.virus.that.causes.AIDS..Retroviruses.can.also.cause.cells.to.become.cancerous,.as.

with.the.viruses.that.cause.some.leukemias.[Columbia.University.Press.2003].

Because.reverse.transcription.lacks.the.usual.“proofreading”.of.DNA.transcription.[Kimball.

2007a],.retroviruses.mutate.frequently.[Drake.1993]..This.allows.the.virus.to.develop.resistance.to.

antiviral.pharmaceuticals.quickly.and.is.one.of.the.main.reasons.why.an.effective.vaccine.for.HIV.

has.not.been.developed.yet.[Coffin.et.al..1997].

Retroviruses.commonly.carry.three.genes.that.encode.proteins.found.in.the.mature.virus:

gag (Group-specific.antigen).codes.for.core.and.structural.proteins.of.the.virus pol (Polymerase).codes.for.reverse transcriptase, protease, and.integrase enzymes eEnv (Envelope).codes.for.the.proteins.used.to.coat.the.retrovirus.[Cann.1999]

RNA.is.considered.more.ancient.than.DNA.[Jeffares.&.Poole.2006]..Some.researchers.speculate.

that.the.processes.used.by.retroviruses.(RNA.to.DNA.to.RNA.to.protein).may.be.the.key.to.the.

evolution.of.DNA;.at.some.time.in.the.distant.past,.retroviruses.may.have.evolved.to.create.DNA.

from.RNA.templates.[Biocrawler.2006].

Intron functions..As.mentioned.earlier,.it.was.once.believed.that.introns.had.no.function,.but.

research.has.increasingly.revealed.significant.roles.played.by.introns.

Some introns.can.promote.the.expression.of.a.neighboring.gene..Introns.are.not.required.

for.gene.expression,.however,.because.several.genes.that.lack.introns.express.themselves.

normally.[DeSouza.1999].

Some introns.contain.genes.for.small.nuclear.RNA,.which.is.important.for.the.translation.

of.messenger.RNA,.an.intermediary.between.DNA.and.proteins.[Ibid].

Nuclear introns.can.also.be.important.in.a.process.called.alternative splicing,.which.can.

produce.multiple.types.of.messenger.RNA.from.a.single.gene.[Ibid].

Some introns.play.a.role.in.the.formation.of.cancer.[Zheng.2006];.some.serve.as.tumor.

suppressors.[Berggen.et.al..2000].

Yet.another.class.of.introns.codes.for.microRNAs (miRNAs)..miRNAs.are.short,.noncoding.RNAs.

that.appear.to.play.a.role.in.suppressing.the.expression.of.certain.proteins.and.may.regulate.the.

formation.of.shape.and.size.in.development..Recent.studies.have.indicated.that.miRNAs.can.also.

activate.gene.expression.at.different.times.in.the.cell.cycle.[Vasudevan.et.al..2007]..miRNAs.exert.

their.effects.by.interacting.with.mRNAs..There.are.over.150.miRNAs.in.humans.alone..It.is.still.

uncertain.what.their.exact.roles.are,.but.they.probably.have.a.role.in.regulating.embryological.devel-opment..It.has.been.shown.that.the.levels.of.certain.miRNAs.are.precisely.regulated.in.mice.as.their.

brains.grow.[Gibbs.2003]..This.is.a.tantalizing.hint.of.the.research.yet.to.come.on.these.interesting.

nucleic.acid.molecules.

The.bottom.line.is.that.genes,.although.an.important.part.of.the.genome,.are.not.the.last.word..

A.great.deal.of.work.remains.to.be.done.on.understanding.introns.as.well.as.exons.

In document Renealmia (página 106-126)