B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 86
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Each deletion removes anaverage of 95 nucleotides of DNA sequence. Only one of these deletions affects aprotein-coding region: the rest are thought to alter regions that affect how nearbygenes are expressed, an expectation that has been experimentally confirmedin a few cases. A large proportion of the presumed regulatory regions identifiedin this way lie near genes that affect neural function and/or near genes involved insteroid signaling, suggesting that changes in the nervous system and in immuneor reproductive functions have played an especially important role in humanevolution.HOW GENOMES EVOLVE227Mutations in the DNA Sequences That Control Gene ExpressionHave Driven Many of the Evolutionary Changes in VertebratesThe vast hoard of genomic sequence data now being accumulated can be exploredin many other ways to reveal events that happened even hundreds of millions ofyears ago.
For example, one can attempt to trace the origins of the regulatory elements in DNA that have played critical parts in vertebrate evolution. One suchstudy began with the identification of nearly 3 million noncoding sequences, averaging 28 base pairs in length, that have been conserved in recent vertebrate evolution while being absent in more ancient ancestors. Each of these special non-coding sequences is likely to represent a functional innovation peculiar to a particularbranch of the vertebrate family tree, and most of them are thought to consist ofregulatory DNA that governs the expression of a neighboring gene. Given fullgenome sequences, one can identify the genes that lie closest and thus appearmost likely to have fallen under the sway of these novel regulatory elements.
Bycomparing many different species, with known divergence times, one can alsoestimate when each such regulatory element came into existence as a conservedfeature. The findings suggest remarkable evolutionary differences between thevarious functional classes of genes (Figure 4–74). Conserved regulatory elementsthat originated early in vertebrate evolution—that is, more than about 300 millionyears ago, which is when the mammalian lineage split from the lineage leading tobirds and reptiles—seem to be mostly associated with genes that code for transcription regulator proteins and for proteins with roles in organizing embryonicdevelopment.
Then came an era when the regulatory DNA innovations arose nextto genes coding for receptors for extracellular signals. Finally, over the course ofthe past 100 million years, the regulatory innovations seem to have been concentrated in the neighborhood of genes coding for proteins (such as protein kinases)that function to modify other proteins post-translationally.Many questions remain to be answered about these phenomena and whatthey mean. One possible interpretation is that the logic—the circuit diagram—ofthe gene regulatory network in vertebrates was established early, and that morerecent evolutionary change has mainly occurred through the tuning of quantitative parameters.
This could help to explain why, among the mammals, for example, the basic body plan—the topology of the tissues and organs—has been largelyconserved.Gene Duplication Also Provides an Important Source of GeneticNovelty During EvolutionEvolution depends on the creation of new genes, as well as on the modificationof those that already exist.
How does this occur? When we compare organismsthat seem very different—a primate with a rodent, for example, or a mouse witha fish—we rarely encounter genes in the one species that have no homolog in thereception ofextracellular signalsHUMANMOUSECOWPLATYPUSCHICKENFROGdevelopment andtranscriptionregulationFISHpost-translationalproteinmodification500400300200100millions of years before present0Figure 4–74 The types of changesin gene regulation inferred to havepredominated during the evolution ofour vertebrate ancestors.
To producethe information summarized in this plot,wherever possible the type of generegulated by each conserved noncodingsequence was inferred from the identity ofits closest protein-coding gene. The fixationtime for each conserved sequence wasthen used to derive the conclusions shown.(Based on C.B. Lowe et al., Science333:1019–1024, 2011. With permissionfrom AAAS.)228Chapter 4: DNA, Chromosomes, and Genomesother. Genes without homologous counterparts are relatively scarce even whenwe compare such divergent organisms as a mammal and a worm.
On the otherhand, we frequently find gene families that have different numbers of members indifferent species. To create such families, genes have been repeatedly duplicated,and the copies have then diverged to take on new functions that often vary fromone species to another.Gene duplication occurs at high rates in all evolutionary lineages, contributingto the vigorous process of DNA addition discussed previously. In a detailed studyof spontaneous duplications in yeast, duplications of 50,000 to 250,000 nucleotidepairs were commonly observed, most of which were tandemly repeated. Theseappeared to result from DNA replication errors that led to the inexact repair ofdouble-strand chromosome breaks.
A comparison of the human and chimpanzeegenomes reveals that, since the time that these two organisms diverged, such segmental duplications have added about 5 million nucleotide pairs to each genomeevery million years, with an average duplication size being about 50,000 nucleotide pairs (although there are some duplications five times larger). In fact, if onecounts nucleotides, duplication events have created more differences betweenour two species than have single-nucleotide substitutions.Duplicated Genes DivergeWhat is the fate of newly duplicated genes? In most cases, there is presumed tobe little or no selection—at least initially—to maintain the duplicated state sinceeither copy can provide an equivalent function. Hence, many duplication eventsare likely to be followed by loss-of-function mutations in one or the other gene.This cycle would functionally restore the one-gene state that preceded the duplication.
Indeed, there are many examples in contemporary genomes where one copyof a duplicated gene can be seen to have become irreversibly inactivated by multiple mutations. Over time, the sequence similarity between such a pseudogeneand the functional gene whose duplication produced it would be expected to beeroded by the accumulation of many mutations in the pseudogene—the homologous relationship eventually 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 genes with related functions in biologically complex organisms, and it is thought to play a critical role in the evolutionof increased biological complexity.
An examination of many different eukaryoticgenomes suggests that the probability that any particular gene will undergo aduplication event that spreads to most or all individuals in a species is approximately 1 percent every million years.Whole-genome duplications offer particularly dramatic examples of the duplication–divergence cycle. A whole-genome duplication can occur quite simply: allthat is required is one round of genome replication in a germ-line cell lineagewithout a corresponding cell division. Initially, the chromosome number simplydoubles.
Such abrupt increases in the ploidy of an organism are common, particularly in fungi and plants. After a whole-genome duplication, all genes existas duplicate copies. However, unless the duplication event occurred so recentlythat there has been little time for subsequent alterations in genome structure,the results of a series of segmental duplications—occurring at different times—are hard to distinguish from the end product of a whole-genome duplication. Inmammals, for example, the role of whole-genome duplications versus a series ofpiecemeal duplications of DNA segments is quite uncertain. Nevertheless, it isclear that a great deal of gene duplication has occurred in the distant past.Analysis of the genome of the zebrafish, in which at least one whole-genomeduplication is thought to have occurred hundreds of millions of years ago, has castsome light on the process of gene duplication and divergence.
Although manyduplicates of zebrafish genes appear to have been lost by mutation, a significantfraction—perhaps as many as 30–50%—have diverged functionally while bothHOW GENOMES EVOLVE229Figure 4–75 A comparison of the structure of one-chain and four-chainglobins. The four-chain globin shown is hemoglobin, which is a complex oftwo α-globin and two β-globin chains. The one-chain globin present in someprimitive vertebrates represents an intermediate in the evolution of the four-chainglobin. With oxygen bound it exists as a monomer; without oxygen it dimerizes.copies have remained active.
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