B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 87
Текст из файла (страница 87)
In many cases, the most obvious functional difference between the duplicated genes is that they are expressed in different tissuesor at different stages of development. One attractive theory to explain such an endresult imagines that different, mildly deleterious mutations occur quickly in bothcopies of a duplicated gene set. For example, one copy might lose expression ina particular tissue as a result of a regulatory mutation, while the other copy losesexpression in a second tissue.
Following such an occurrence, both gene copieswould be required to provide the full range of functions that were once suppliedby a single gene; hence, both copies would now be protected from loss throughinactivating mutations. Over a longer period, each copy could then undergo further changes through which it could acquire new, specialized features.single-chain globin bindsone oxygen moleculeoxygenbinding siteon hemeEVOLUTION OF ASECOND GLOBINCHAIN BYGENE DUPLICATIONFOLLOWED BYMUTATIONββThe Evolution of the Globin Gene Family Shows How DNADuplications Contribute to the Evolution of Organismsααfour-chain globin binds fouroxygen molecules in acooperative mannerchromosome16chromosome11variouseg G gAa genesMBoC6 m4.86/4.74d100millions of years agoThe globin gene family provides an especially good example of how DNA duplication generates new proteins, because its evolutionary history has been workedout particularly well.
The unmistakable similarities in amino acid sequence andstructure among the present-day globins indicate that they all must derive from acommon ancestral gene, even though some are now encoded by widely separatedgenes in the mammalian genome.We can reconstruct some of the past events that produced the various typesof oxygen-carrying hemoglobin molecules by considering the different forms ofthe protein in organisms at different positions on the tree of life. A molecule likehemoglobin was necessary to allow multicellular animals to grow to a large size,since large animals cannot simply rely on the diffusion of oxygen through thebody surface to oxygenate their tissues adequately. But oxygen plays a vital part inthe life of nearly all living organisms, and oxygen-binding proteins homologous tohemoglobin can be recognized even in plants, fungi, and bacteria.
In animals, themost primitive oxygen-carrying molecule is a globin polypeptide chain of about150 amino acids that is found in many marine worms, insects, and primitive fish.The hemoglobin molecule in more complex vertebrates, however, is composed oftwo kinds of globin chains. It appears that about 500 million years ago, during thecontinuing evolution of fish, a series of gene mutations and duplications occurred.These events established two slightly different globin genes in the genome of eachindividual, coding for α- and β-globin chains that associate to form a hemoglobinmolecule consisting of two α chains and two β chains (Figure 4–75).
The four oxygen-binding sites in the α2β2 molecule interact, allowing a cooperative allostericchange in the molecule as it binds and releases oxygen, which enables hemoglobin to take up and release oxygen more efficiently than the single-chain version.Still later, during the evolution of mammals, the β-chain gene apparentlyunderwent duplication and mutation to give rise to a second β-like chain thatis synthesized specifically in the fetus.
The resulting hemoglobin molecule has ahigher affinity for oxygen than adult hemoglobin and thus helps in the transferof oxygen from the mother to the fetus. The gene for the new β-like chain subsequently duplicated and mutated again to produce two new genes, ε and γ, the εchain being produced earlier in development (to form α2ε2) than the fetal γ chain,which forms α2γ2.
A duplication of the adult β-chain gene occurred still later,during primate evolution, to give rise to a δ-globin gene and thus to a minor formof hemoglobin (α2δ2) that is found only in adult primates (Figure 4–76).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 expression of the gene.badultbfetalb300a500translocationseparating aand b genesbsingle-chainglobin700Figure 4–76 An evolutionary schemefor the globin chains that carry oxygenin the blood of animals.
The schemeemphasizes the β-like globin gene family.A relatively recent gene duplication of theγ-chain gene produced γG and γA, whichare fetal β-like chains of identical function.The location of the globin genes in thehuman genome is shown at the top ofthe figure.230Chapter 4: DNA, Chromosomes, and GenomesAs a result, each globin is made in different amounts at different times of humandevelopment.The history of these gene duplications is reflected in the arrangement of hemoglobin genes in the genome. In the human genome, the genes that arose from theoriginal β gene are arranged as a series of homologous DNA sequences locatedwithin 50,000 nucleotide pairs of one another on a single chromosome.
A similarcluster of human α-globin genes is located on a separate chromosome. Not onlyother mammals, but birds too have their α- and β-globin gene clusters on separate chromosomes. In the frog Xenopus, however, they are together, suggestingthat a chromosome translocation event in the lineage of birds and mammals separated the two gene clusters about 300 million years ago, soon after our ancestorsdiverged from amphibians (see Figure 4–76).There are several duplicated globin DNA sequences in the α- and β-globingene clusters that are not functional genes but pseudogenes. These have a closesequence similarity to the functional genes but have been disabled by mutations that prevent their expression as functional proteins.
The existence of suchpseudogenes makes it clear that, as expected, not every DNA duplication leads toa new functional gene.Genes Encoding New Proteins Can Be Created by theRecombination of ExonsThe role of DNA duplication in evolution is not confined to the expansion ofgene families. It can also act on a smaller scale to create single genes by stringing together short duplicated segments of DNA. The proteins encoded by genesgenerated in this way can be recognized by the presence of repeating similar protein domains, which are covalently linked to one another in series.
The immunoglobulins (Figure 4–77), for example, as well as most fibrous proteins (such ascollagens) are encoded by genes that have evolved by repeated duplications of aprimordial DNA sequence.In genes that have evolved in this way, as well as in many other genes, eachseparate exon often encodes an individual protein folding unit, or domain. It isbelieved that the organization of DNA coding sequences as a series of such exonsseparated by long introns has greatly facilitated the evolution of new proteins.
Theduplications necessary to form a single gene coding for a protein with repeatingdomains, for example, can easily occur by breaking and rejoining the DNA anywhere in the long introns on either side of an exon; without introns there would beonly a few sites in the original gene at which a recombinational exchange betweenDNA molecules could duplicate the domain and not disrupt it. By enabling theduplication to occur by recombination at many potential sites rather than just afew, introns increase the probability of a favorable duplication event.More generally, we know from genome sequences that the various parts ofgenes—both their individual exons and their regulatory elements—have servedas modular elements that have been duplicated and moved about the genometo create the great diversity of living things.
Thus, for example, many present-dayproteins are formed as a patchwork of domains from different origins, reflectingtheir complex evolutionary history (see Figure 3–17).Neutral Mutations Often Spread to Become Fixed in a Population,with a Probability That Depends on Population Sizeheavy chainH 2NH2NNH2NH2In comparisons between two species that have diverged from one another by millions of years, it makes little difference which individuals from each species areFigure 4–77 Schematic view of an antibody (immunoglobulin) molecule.This molecule is a complex of two identical heavy chains and two identicallight chains.
Each heavy chain contains four similar, covalently linkeddomains, while each light chain contains two such domains. Each domainis encoded by a separate exon, and all of the exons are thought to haveevolved by the serial duplication of a single ancestral exon.light chainHOOCCOOHHOW GENOMES EVOLVEcompared. For example, typical human and chimpanzee DNA sequences differfrom one another by about 1%. In contrast, when the same region of the genomeis sampled from two randomly chosen humans, the differences are typically about0.1%. For more distantly related organisms, the interspecies differences outshineintraspecies variation even more dramatically.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
