B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 82
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The sequencing of the genomes of thousands of organisms is revolutionizing our view of the process of evolution, uncovering an astonishing wealth of information about not only family relationshipsamong organisms, but also about the molecular mechanisms by which evolutionhas proceeded.It is perhaps not surprising that genes with similar functions can be found ina diverse range of living things.
But the great revelation of the past 30 years hasbeen the extent to which the actual nucleotide sequences of many genes havebeen conserved. Homologous genes—that is, genes that are similar in both theirnucleotide sequence and function because of a common ancestry—can often berecognized across vast phylogenetic distances. Unmistakable homologs of manyhuman genes are present in organisms as diverse as nematode worms, fruit flies,yeasts, and even bacteria. In many cases, the resemblance is so close that, forexample, the protein-coding portion of a yeast gene can be substituted with itshuman homolog—even though humans and yeast are separated by more than abillion years of evolutionary history.As emphasized in Chapter 3, the recognition of sequence similarity hasbecome a major tool for inferring gene and protein function.
Although a sequencematch does not guarantee similarity in function, it has proved to be an excellentclue. Thus, it is often possible to predict the function of genes in humans for whichno biochemical or genetic information is available simply by comparing theirHOW GENOMES EVOLVEnucleotide sequences with the sequences of genes that have been characterizedin other more readily studied organisms.In general, the sequences of individual genes are much more tightly conserved than is overall genome structure.
Features of genome organization suchas genome size, number of chromosomes, order of genes along chromosomes,abundance and size of introns, and amount of repetitive DNA are found to differgreatly when comparing distant organisms, as does the number of genes that eachorganism contains.Genome Comparisons Reveal Functional DNA Sequences by theirConservation Throughout EvolutionA first obstacle in interpreting the sequence of the 3.2 billion nucleotide pairs inthe human genome is the fact that much of it is probably functionally unimportant.
The regions of the genome that code for the amino acid sequences of proteins(the exons) are typically found in short segments (average size about 145 nucleotide pairs), small islands in a sea of DNA whose exact nucleotide sequence isthought to be mostly of little consequence. This arrangement makes it difficultto identify all the exons in a stretch of DNA, and it is often hard too to determineexactly where a gene begins and ends.One very important approach to deciphering our genome is to search for DNAsequences that are closely similar between different species, on the principlethat DNA sequences that have a function are much more likely to be conservedthan those without a function.
For example, humans and mice are thought tohave diverged from a common mammalian ancestor about 80 × 106 years ago,which is long enough for the majority of nucleotides in their genomes to havebeen changed by random mutational events. Consequently, the only regions thatwill have remained closely similar in the two genomes are those in which mutations would have impaired function and put the animals carrying them at a disadvantage, resulting in their elimination from the population by natural selection.Such closely similar pieces of DNA sequence are known as conserved regions.
Inaddition to revealing those DNA sequences that encode functionally importantexons and RNA molecules, these conserved regions will include regulatory DNAsequences as well as DNA sequences with functions that are not yet known. Incontrast, most nonconserved regions will reflect DNA whose sequence is muchless likely to be critical for function.The power of this method can be increased by including in such comparisonsthe genomes of large numbers of species whose genomes have been sequenced,such as rat, chicken, fish, dog, and chimpanzee, as well as mouse and human.By revealing in this way the results of a very long natural “experiment,” lastingfor hundreds of millions of years, such comparative DNA sequencing studieshave highlighted the most interesting regions in our genome.
The comparisonsreveal that roughly 5% of the human genome consists of “multispecies conservedsequences.” To our great surprise, only about one-third of these sequences codefor proteins (see Table 4–1, p. 184). Many of the remaining conserved sequencesconsist of DNA containing clusters of protein-binding sites that are involved ingene regulation, while others produce RNA molecules that are not translatedinto protein but are important for other known purposes.
But, even in the mostintensively studied species, the function of the majority of these highly conservedsequences remains unknown. This remarkable discovery has led scientists to conclude that we understand much less about the cell biology of vertebrates than wehad thought.
Certainly, there are enormous opportunities for new discoveries,and we should expect many more surprises ahead.Genome Alterations Are Caused by Failures of the NormalMechanisms for Copying and Maintaining DNA, as well as byTransposable DNA ElementsEvolution depends on accidents and mistakes followed by nonrandom survival.Most of the genetic changes that occur result simply from failures in the normal217218Chapter 4: DNA, Chromosomes, and Genomesmechanisms by which genomes are copied or repaired when damaged, althoughthe movement of transposable DNA elements (discussed below) also plays animportant part.
As we will explain in Chapter 5, the mechanisms that maintainDNA sequences are remarkably precise—but they are not perfect. DNA sequencesare inherited with such extraordinary fidelity that typically, along a given line ofdescent, only about one nucleotide pair in a thousand is randomly changed in thegerm line every million years. Even so, in a population of 10,000 diploid individuals, every possible nucleotide substitution will have been “tried out” on about 20occasions in the course of a million years—a short span of time in relation to theevolution of species.Errors in DNA replication, DNA recombination, or DNA repair can lead eitherto simple local changes in DNA sequence—so-called point mutations such as thesubstitution of one base pair for another—or to large-scale genome rearrangements such as deletions, duplications, inversions, and translocations of DNA fromone chromosome to another.
In addition to these failures of the genetic machinery, genomes contain mobile DNA elements that are an important source ofgenomic change (see Table 5–3, p. 267). These transposable DNA elements (transposons) are parasitic DNA sequences that can spread within the genomes theycolonize. In the process, they often disrupt the function or alter the regulationof existing genes. On occasion, they have created altogether novel genes throughfusions between transposon sequences and segments of existing genes. Over longperiods of evolutionary time, DNA transposition events have profoundly affectedgenomes, so much so that nearly half of the DNA in the human genome consistsof recognizable relics of past transposition events (Figure 4–62).
Even more of ourgenome is thought to have been derived from transpositions that occurred so longago (>108 years) that the sequences can no longer be traced to transposons.The Genome Sequences of Two Species Differ in Proportion to theLength of Time Since They Have Separately EvolvedThe differences between the genomes of species alive today have accumulatedover more than 3 billion years. Although we lack a direct record of changes overtime, scientists can reconstruct the process of genome evolution from detailedcomparisons of the genomes of contemporary organisms.The basic organizing framework for comparative genomics is the phylogenetic tree. A simple example is the tree describing the divergence of humans fromthe great apes (Figure 4–63).
The primary support for this tree comes from comparisons of gene or protein sequences. For example, comparisons between thesequences of human genes or proteins and those of the great apes typically revealthe fewest differences between human and chimpanzee and the most betweenhuman and orangutan.For closely related organisms such as humans and chimpanzees, it is relativelyeasy to reconstruct the gene sequences of the extinct, last common ancestor of thetwo species (Figure 4–64). The close similarity between human and chimpanzeegenes is mainly due to the short time that has been available for the accumulationof mutations in the two diverging lineages, rather than to functional constraintspercentage010203040LINEsSINEsretroviral-like elementsDNA-only transposon “fossils”TRANSPOSONSsimple sequence repeatssegmental duplicationsREPEATED SEQUENCES5060708090intronsprotein-coding regionsGENESnonrepetitive DNA that isneither in introns nor codonsUNIQUE SEQUENCES100Figure 4–62 A representation of thenucleotide sequence content of thesequenced human genome.
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