B. Alberts, A. Johnson, J. Lewis и др. - Molecular Biology of The Cell (6th edition) (1120996), страница 84
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Figure 4–67 illustrates how segments of the different mouse chromosomes map onto the human chromosome set. For much more distantly relatedvertebrates, such as chicken and human, the number of breakage-and-rejoiningevents has been much greater and the regions of synteny are much shorter; inaddition, they are often hard to discern because of the divergence of the DNAsequences that they contain.An unexpected conclusion from a detailed comparison of the complete mouseand human genome sequences, confirmed by subsequent comparisons betweenthe genomes of other vertebrates, is that small blocks of DNA sequence are beingdeleted from and added to genomes at a surprisingly rapid rate. Thus, if weassume that our common ancestor had a genome of human size (about 3.2 billionnucleotide pairs), mice would have lost a total of about 45% of that genome fromaccumulated deletions during the past 80 million years, while humans wouldhave lost about 25%.
However, substantial sequence gains from many small chromosome duplications and from the multiplication of transposons have compensated for these deletions. As a result, our genome size is thought to be practicallyunchanged from that of the last common ancestor of humans and mice, while themouse genome is smaller by only about 0.3 billion nucleotides.Figure 4–66 A phylogenetic tree showingthe evolutionary relationships of somepresent-day mammals. The length ofeach line is proportional to the number of“neutral substitutions”—that is, nucleotidechanges at sites where there is assumedto be no purifying selection. (Adapted fromG.M.
Cooper et al., Genome Res.15:901–913, 2005. With permission fromCold Spring Harbor Laboratory Press.)Chapter 4: DNA, Chromosomes, and Genomes222Figure 4–67 Synteny between humanand mouse chromosomes. In thisdiagram, the human chromosome setis shown above, with each part of eachchromosome colored according to themouse chromosome with which it issyntenic. The color coding used for eachmouse chromosome is shown below.Heterochromatic highly repetitive regions(such as centromeres) that are difficult tosequence cannot be mapped in this way;these are colored black. (Adapted fromE.E. Eichler and D. Sankoff, Science301:793–797, 2003.
With permissionfrom AAAS.)1234mousechromosomeindex5 67813429 10 11 12 13 14 15 16 17 18 19 20 21 22 X56789 10 11 12 13 14 15 16 17 18 19 XGood evidence for the loss of DNA sequences in small blocks during evolutioncan be obtained from a detailed comparison of regions of synteny in the humanand mouse genomes. The comparative shrinkage of the mouse genome can beMBoC6 m4.601/4.66clearly seen from such comparisons,with the net loss of sequences scatteredthroughout the long stretches of DNA that are otherwise homologous (Figure4–68).DNA is added to genomes both by the spontaneous duplication of chromosomal segments that are typically tens of thousands of nucleotide pairs long(as will be discussed shortly) and by insertion of new copies of active transposons.Most transposition events are duplicative, because the original copy of thetransposon stays where it was when a copy inserts at the new site; see, for example, Figure 5–63.
Comparison of the DNA sequences derived from transposonsin the human and the mouse readily reveals some of the sequence additions(Figure 4–69).It remains a mystery why all mammals have maintained genome sizes ofroughly 3 billion nucleotide pairs that contain nearly identical sets of genes,even though only approximately 150 million nucleotide pairs appear to be undersequence-specific functional constraints.The Size of a Vertebrate Genome Reflects the Relative Rates ofDNA Addition and DNA Loss in a LineageIn more distantly related vertebrates, genome size can vary considerably, apparently without a drastic effect on the organism or its number of genes. Thus, thechicken genome, at one billion nucleotide pairs, is only about one-third the sizehuman chromosome 14mouse chromosome 12200,000 basesFigure 4–68 Comparison of a syntenicportion of mouse and human genomes.About 90% of the two genomes can bealigned in this way.
Note that while thereis an identical order of the matched indexsequences (red marks), there has been anet loss of DNA in the mouse lineage thatis interspersed throughout the entire region.This type of net loss is typical for all suchregions, and it accounts for the fact that themouse genome contains 14% less DNA thandoes the human genome. (Adapted fromMouse Genome Sequencing Consortium,Nature 420:520–562, 2002.
With permissionfrom Macmillan Publishers Ltd.)HOW GENOMES EVOLVE223human β-globin gene clusterγGεγAδβmouse β-globin gene clusterεγβmajorβminor10,000nucleotide pairsof the mammalian genome. An extreme example is the puffer fish, Fugu rubripes(Figure 4–70), which has a tiny genome for a vertebrate (0.4 billion nucleotidepairs compared to 1 billion or more for many other fish).
The small size of the FuguMBoC6m4.80/4.68genome is largely dueto thesmall size of its introns. Specifically, Fugu introns, aswell as other noncoding segments of the Fugu genome, lack the repetitive DNAthat makes up a large portion of the genomes of most well-studied vertebrates.Nevertheless, the positions of the Fugu introns between the exons of each geneare almost the same as in mammalian genomes (Figure 4–71).While initially a mystery, we now have a simple explanation for such large differences in genome size between similar organisms: because all vertebrates experience a continuous process of DNA loss and DNA addition, the size of a genomemerely depends on the balance between these opposing processes acting overmillions of years.
Suppose, for example, that in the lineage leading to Fugu, therate of DNA addition happened to slow greatly. Over long periods of time, thiswould result in a major “cleansing” from this fish genome of those DNA sequenceswhose loss could be tolerated. The result is an unusually compact genome, relatively free of junk and clutter, but retaining through purifying selection the vertebrate DNA sequences that are functionally important. This makes Fugu, withits 400 million nucleotide pairs of DNA, a valuable resource for genome researchaimed at understanding humans.Figure 4–69 A comparison of theβ-globin gene cluster in the humanand mouse genomes, showing thelocations of transposable elements.
Thisstretch of the human genome contains fivefunctional β-globin-like genes (orange);the comparable region from the mousegenome has only four. The positions ofthe human Alu sequences are indicatedby green circles, and the human L1sequences by red circles. The mousegenome contains different but relatedtransposable elements: the positions ofB1 elements (which are related to thehuman Alu sequences) are indicated byblue triangles, and the positions of themouse L1 elements (which are related tothe human L1 sequences) are indicatedby orange triangles.
The absence oftransposable elements from the globinstructural genes can be attributed topurifying selection, which would haveeliminated any insertion that compromisedgene function. (Courtesy of Ross Hardisonand Webb Miller.)We Can Infer the Sequence of Some Ancient GenomesThe genomes of ancestral organisms can be inferred, but most can never bedirectly observed. DNA is very stable compared with most organic molecules,but it is not perfectly stable, and its progressive degradation, even under the bestcircumstances, means that it is virtually impossible to extract sequence information from fossils that are more than a million years old. Although a modernorganism such as the horseshoe crab looks remarkably similar to fossil ancestorsthat lived 200 million years ago, there is every reason to believe that the horseshoe-crab genome has been changing during all that time in much the same wayas in other evolutionary lineages, and at a similar rate.
Selection must have maintained key functional properties of the horseshoe-crab genome to account for themorphological stability of the lineage. However, comparisons between differentpresent-day organisms show that the fraction of the genome subject to purifyingselection is small; hence, it is fair to assume that the genome of the modern horseshoe crab, while preserving features critical for function, must differ greatly fromthat of its extinct ancestors, known to us only through the fossil record.It is possible to get direct sequence information by examining DNA samplesfrom ancient materials if these are not too old.
In recent years, technical advanceshave allowed DNA sequencing from exceptionally well-preserved bone fragmentsthat date from more than 100,000 years ago. Although any DNA this old will beimperfectly preserved, a sequence of the Neanderthal genome has been reconstructed from many millions of short DNA sequences, revealing—among otherthings—that our human ancestors interbred with Neanderthals in Europe andFigure 4–70 The puffer fish, Fugurubripes.
(Courtesy of Byrappa Venkatesh.)224Chapter 4: DNA, Chromosomes, and Genomeshuman geneFugu gene0.0100.0thousands of nucleotide pairs180.0that modern humans have inherited specific genes from them (Figure 4–72). Theaverage difference in DNA sequence between humans and Neanderthals showsthat our two lineages diverged somewhere between 270,000 and 440,000 yearsago, well before the time that humans are believed to have migrated out of Africa.But what about decipheringthem4.82/4.70genomes of much older ancestors, those forMBoC6which no useful DNA samples can be isolated? For organisms that are as closelyrelated as human and chimpanzee, we saw that this may not be difficult: referenceto the gorilla sequence can be used to sort out which of the few sequence differences between human and chimpanzee are inherited from our common ancestorsome 6 million years ago (see Figure 4–64).
And for an ancestor that has produceda large number of different organisms alive today, the DNA sequences of manyspecies can be compared simultaneously to unscramble much of the ancestralsequence, allowing scientists to derive DNA sequences much farther back in time.For example, from the genome sequences currently being obtained for dozens ofmodern placental mammals, it should be possible to infer much of the genomesequence of their 100 million-year-old common ancestor—the precursor of species as diverse as dog, mouse, rabbit, armadillo, and human (see Figure 4–66).Multispecies Sequence Comparisons Identify Conserved DNASequences of Unknown FunctionThe mass of DNA sequence now in databases (hundreds of billions of nucleotidepairs) provides a rich resource that scientists can mine for many purposes.
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