Часть 1 (1120999), страница 83
Текст из файла (страница 83)
Hence, many duplication events are likely to be followed by lossof-function mutations in one or the other gene. This cycle would functionallyrestore the one-gene state that preceded the duplication. Indeed, there are manyexamplesin contemporary genomeswhere one copy of a duplicated gene can beseen to have become irreversibly inactivated by multiple mutations. Over time,the sequence similarity between such a pseudogene and the functional genewhose duplication produced it would be expected to be eroded by the accumulation of many mutations in the pseudogene-the homologous relationshipeventually becoming undetectable.An alternative fate for gene duplications is for both copies to remain functional, while diverging in their sequence and pattern of expression,thus takingon different roles.
This process of "duplication and divergence" almost certainlyexplains the presence of large families of geneswith related functions in biologically complex organisms, and it is thought to play a critical role in the evolutionof increasedbiological complexity. An examination of many different eucaryoticgenomes suggeststhat the probability that any particular gene will undergo aduplication event that spreadsto most or all individuals in a speciesis approximately l% every million years.\.Vhole-genome duplications offer particularly dramatic examples of theduplication-divergence cycle.
A whole-genome duplication can occur quitesimply: all that is required is one round of genome replication in a germline celllineage without a corresponding cell division. Initially, the chromosome numbersimply doubles. Such abrupt increases in the ploidy of an organism are common, particularly in fungi and plants. After a whole-genome duplication, allgenes exist as duplicate copies. However, unless the duplication event occurredso recently that there has been little time for subsequent alterations in genomestructure, the results of a series of segmental duplications-occurring at different times-are very hard to distinguish from the end product of a wholegenome duplication.
In mammals, for example,the role of whole-genome duplications versus a series of piecemeal duplications of DNA segments is quiteuncertain. Nevertheless, it is clear that a great deal of gene duplication hasocurred in the distant past.Analysis of the genome of the zebrafish, in which either a whole-genomeduplication or a seriesof more local duplications occurred hundreds of millionsof years ago, has cast some light on the process of gene duplication and divergence.Although many duplicates ofzebrafish genes appear to have been lost bymutation, a significant fraction-perhaps as many as 30-50%-have divergedfunctionally while both copies have remained active.
In many cases,the mostobvious functional difference between the duplicated genes is that they areexpressedin different tissues or at different stagesof development (see Figure22-46). One attractive theory to explain such an end result imagines that different, mildly deleterious mutations occur quickly in both copies of a duplicatedgene set. For example, one copy might lose expressionin a particular tissue as aresult of a regulatory mutation, while the other copy losesexpressionin a secondtissue.
Following such an occurrence, both gene copies would be required toprovide the full range of functions that were once supplied by a single gene;hence, both copies would now be protected from loss through inactivatingmutations. Over a longer period, each copy could then undergo further changesthrough which it could acquire new, specializedfeatures.IIIhumanwormflvm o r et h a n 2 0 0worm genes30 more genesFigure4-85 A phylogenetictree basedon the inferred protein sequencesfor allnuclearhormone receptorsencoded inthe genomesof human (H.
saqiens),anematodeworm (C.elegansl,and a fruitTrianglesrepresentfly (D.melanogoster).proteinsubfamiliesthat haveexpandedlineages;within individualevolutionarythethe width of thesetrianglesindicatesnumberof genesencodingmembersofColoredverticalbarsthesesubfamilies.representa singlegene.Thereis nosimplepatternto the historicalthat haveand divergencesduplicationscreatedthe genefamiliesencodingnuclearreceptorsin the threeThefamilyoforganisms.contemporarynuclearhormonereceptorsis describedin Figure15-14.Theseproteinsfunctionin cellsignalingand generegulation.(Adaptedfrom InternationalHumanNotu/eConsortium,GenomeSequencing2001.With permissionfrom409:860-921,Ltd.)MacmillanPublishers256Chapter4: DNA,Chromosomes,and GenomesFigure4-86 A comparisonof the structureof one-chainand four-chainglobins.Thefour-chainglobinshownis hemoglobin,whichis a complexoftwo o-globinand two p-globinchains.Theone-chainglobinin someprimitivevertebratesformsa dimerthat dissociateswhen it bindsoxygen,representingan intermediatein the evolutionof the four-chainqlobin.s i n g l e - c h a ignl o b i n b i n d so n e o x y g e nm o l e c u l eTheEvolutionof the GlobinGeneFamilyShowsHowDNADuplicationsContributeto the Evolutionof OrganismsThe globin gene family provides an especially good example of how DNA duplication generatesnew proteins, becauseits evolutionary history has been workedout particularlywell.
The unmistakable similarities in amino acid sequence andstructure among the present-day globins indicate that they all must derive froma common ancestral gene, even though some are now encoded by widely separated genes in the mammalian genome.We can reconstruct some of the past events that produced the various t),pesof oxygen-carrying hemoglobin molecules by considering the different forms ofthe protein in organisms at different positions on the phylogenetic tree of life.
Amolecule like hemoglobin was necessaryto allow multicellular animals to growto a large size,since large animals could no longer rely on the simple diffusion ofoxygen through the body surface to oxygenate their tissues adequately. Consequently, hemoglobin-like molecules are found in all vertebrates and in manyinvertebrates.
The most primitive oxygen-carrying molecule in animals is aglobin polypeptide chain of about 150 amino acids, which is found in manymarine worms, insects, and primitive fish. The hemoglobin molecule in morecomplex vertebrates, however, is composed of two kinds of globin chains. Itappears that about 500 million years ago, during the continuing evolution offish, a series of gene mutations and duplications occurred.
These events established two slightly different globin genes,coding for the cr- and B-globin chains,in the genome of each individual. In modern vertebrates, each hemoglobinmolecule is a complex of two cr chains and two B chains (Figure 4-86). The fouroxygen-binding sites in the u2B2 molecule interact, allowing a cooperativeallosteric change in the molecule as it binds and releasesoxygen,which enableshemoglobin to take up and releaseoxygen more efficiently than the single-chainversion.Still later, during the evolution of mammals, the B-chain gene apparentlyunderwent duplication and mutation to give rise to a second B-like chain thatis synthesized specifically in the fetus.
The resulting hemoglobin molecule hasa higher affinity for oxygen than adult hemoglobin and thus helps in the transfer of oxygen from the mother to the fetus. The gene for the new B-like chainsubsequently duplicated and mutated again to produce two new genes, e andT, the s chain being produced earlier in development (to form cr2e2)than thefetal y chain, which forms cx2y2.A duplication of the adult B-chain geneoccurred still later, during primate evolution, to give rise to a 6-globin geneand thus to a minor form of hemoglobin (crz6z)that is found only in adult primates (Figure 4-87).Each of these duplicated genes has been modified by point mutations thataffect the properties of the final hemoglobin molecule, as well as by changes inregulatory regions that determine the timing and level of expressionof the gene.As a result, each globin is made in different amounts at different times of humandevelopment (seeFigure 7-648).The end result of the gene duplication processesthat have given rise to thediversity of globin chains is seen clearly in the human genes that arose fromoxygenb i n d i n gs i t eon hemeE V O L U T I OON FASECONDGLOBINC H A I NB YG E N ED U P L I C A T I O NFOLLOWEBDYMUTATIONf o u r - c h a i ng l o b i n b i n d sf o u ro x y g e nm o l e c u l e si n ac o o p e r a u v em a n n e rcnromoS0metovanouSc genescnromosome1'l.F^Att6pw100ooF rooFigure4-87 An evolutionaryschemefor the globin chainsthat carryoxygenin the blood of animals.The schemeemphasizesthe p-likeglobingenefamily.A relativelyrecentgeneduplicationof the y-chaingeneproducedf and /, whicharefetalp-likechainsof identicalfunction.Thelocationof the globingenesin the humangenomeis shownat the top ofthe figure(seealsoFigure7-64).E= )uuEtranslocationseparatingrxand p geness i n gl e - c h aniglobin257HOW GENOMESEVOLVEthe original B gene, which are arranged as a series of homologous DNAsequences located within 50,000 nucleotide pairs of one another.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
