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The maintenance and modification of these regulatory processes and their influence on genome evolution requires further investigation. Integrating genome-wide maps of CREs, TF binding, and expression with recent advances in techniques for determining in vivo chromatin conformation of DNA [ 36 ] may provide a promising framework for modeling the influence of gene regulation on genome evolution.

A recent study of chromatin looping in multiple human and mouse tissues found significant conservation of gene activity within local topological domains across cells and species [ 37 ]. These results suggest that, as is true for proteins, the 3D structure of regulatory neighborhoods maybe more deeply conserved and important for function than the sequence-level conservation of individual CREs.

Integrating data about genome structure and CREs across many individuals will likely lead to better models of regulatory sequence evolution and how selection acts on gene expression across evolutionary time and tissues. The human body contains hundreds of different cell types with diverse forms and functions, yet each cell contains essentially the same genome. The past decade has seen increasing appreciation for the role of DNA and histone modifications, such as methylation and acetylation, in the diverse gene expression programs observed across different cell types within complex organisms [ 38 — 40 ].

These modifications can be influenced by environmental factors [ 41 ] and in some cases inherited across generations, though the extent of trans-generational inheritance in humans is still unclear [ 42 ]. In spite of extensive work linking these modifications to nearly all processes of development, aging, and disease [ 39 , 43 — 45 ], the influence of these modifications on patterns of genome sequence evolution has received comparatively little attention.

For example, the extent to which the potential for chemical modification places constraint on DNA sequence patterns, e. Several recent studies have explored the degree of conservation of DNA and histone modifications across humans and closely related species [ 31 , 33 , 34 , 46 — 48 ]; changes to the modification status of orthologous regions are common between closely related species and, for DNA methylation, there is a positive correlation between sequence variation and promoter methylation changes.

However, even in the presence of deep sequence conservation, many sites show differential modification. Much work remains to model the evolution of these modifications between individuals and species and to identify associated sequence constraints or lack thereof. Understanding the evolution of these modifications may help resolve debates about whether specific modifications are causal or are the result of other processes like TF binding and transcription [ 49 ].

The majority of human phenotypes of clinical and evolutionary interest are specified by multiple loci across the human genome. Developing models that account for relationships between multiple genetic variants and phenotypes will be critical to fully dissecting the evolution and complex genetic architecture of most human traits.

For example, pleiotropy—when a locus influences multiple independent traits—is found throughout the human genome; however, there is still considerable uncertainty about its prevalence and influence on genome evolution [ 50 — 53 ]. Similarly, epistasis—a non-additive interaction between genetic variants—is common in model organisms, but its influence on human traits has been controversial due to a number of technical and biological factors that can confound current tests for interactions between variants [ 54 , 55 ].

Genome evolution

Each of these areas is in need of new statistical approaches that update existing models to make full use of the wealth of genotype and phenotype data that have become available in the last five years. There is considerable variation in the rate and pattern of substitution along the human genome. Failure to account for these biases can confound tests for selection, complicate demographic inference, and weaken power in association tests [ 7 ]. One of the most potentially influential mutational biases is a recombination-associated process called GC-biased gene conversion gBGC.

The action of gBGC is widespread in human populations and across diverse species [ 58 — 60 ]. Genome-wide modeling of gBGC has demonstrated differences in its strength across the human and chimpanzee lineages [ 59 ] and between different human populations [ 61 , 62 ]. The evolution and effects of gBGC are intimately tied to the dynamics of recombination, which vary considerably in rate along the genome within human populations and between closely related species [ 63 ].

Recombination patterns influence many drivers of genome evolution, including the efficacy of selection, mutation rates, and the accumulation of deleterious mutations [ 64 , 65 ]. In humans, the fast evolving PRDM9 protein directs recombination to specific hotspots based on the occurrence of a GC-rich motif [ 66 ]. Using modern and archaic genome sequences, modeling suggests that gBGC degrades the PRDM9 motif over time and that this may drive the rapid turnover of the recombination landscape in human populations [ 67 ].

Recent direct estimates from trios indicate that the human germline mutation rate is only half of what is expected from phylogenetic estimates [ 68 ], and analysis of whole genome sequence data suggests the evolution of population-specific mutation rates since the divergence of Europeans and Asians [ 69 ]. These results underscore the need for further study of the dynamics and causes of human mutation rate variation across evolutionary time and genomic space. We need to develop high-resolution maps of mutation rates in different populations, better models of how it interacts with selection and recombination, and most importantly, a deeper understanding of its effects on organismal fitness.

The initial comparison of the draft human and chimpanzee genomes identified approximately 35 million single nucleotide polymorphisms SNPs , 5 million small insertions and deletions indels , and hundreds of larger structural variants SVs. Indels and large SVs account for far more nucleotide differences between the human and chimpanzee genomes than SNPs [ 70 ] and have restructured the genomes of great apes [ 71 ]. Recent work on de novo rates of indels and SVs in human populations found that structural changes are much more rare and occur at lower frequency than SNPs; nonetheless, they influence an average of 4.

Indels and large SVs including copy number variants, inversions, and other genomic rearrangements are more likely to cause disease and have been hypothesized to have a greater influence on recent human evolution than SNPs [ 73 , 74 ]. Indeed, many human- and population-specific SVs have been tied to human-specific phenotypes [ 75 ], e. It has also been suggested that de novo creation of new genes is more common than previously appreciated; tens of new human-specific genes have been detected, with particular enrichment for expression in the brain and testes [ 77 , 78 ].

In spite of the potential importance of indels, large SVs, and new genes to phenotypic differences between human individuals and between closely related species, they have received considerably less attention in evolutionary modeling and testing for association with disease than SNPs.

Developing appropriate models for the evolution of indels and SVs faces several challenges including the difficulty of accurately identifying them in short read sequencing data, the diversity of mechanisms that generate them, and their highly heterogeneous mutation rates and distributions along the genome [ 72 , 79 ].

Nevertheless, it is essential to develop evolutionary models akin to those in common use for testing hypotheses about patterns of single nucleotide variant evolution and association with disease for indels and SVs. Sufficiently accurate maps of these events across hundreds of humans are now becoming available [ 79 , 80 ]; these data should facilitate the development of new modeling approaches. Sequencing the genomes of thousands of humans, several archaic humans, and our closest great ape relatives has revealed thousands of loci in the human genome that have experienced accelerated evolution on the human lineage and hundreds more with signatures of recent positive selection [ 81 — 83 ].

These loci hold the promise of explaining much of human-specific biology, and many hypotheses have been proposed about their effects [ 75 ]. However, beyond a handful of successes that involved detailed experimental validation [ 76 , 84 — 88 ], connecting these mutations to effects on human phenotypes has been difficult. The first obstacle comes from the fact that the vast majority of these regions are non-coding and have minimal functional annotation. Furthermore, most human-specific traits have complex genetic architectures in which many coding and non-coding loci influence the phenotype [ 89 ].

Finally, appropriate model systems in which to test potential effects of mutations are not available for many phenotypes, and it is challenging to test variants in a high throughput manner in available systems. Algorithmic and experimental innovations paired with increases in available phenotype and functional genomic data will significantly increase the pace with which human-specific variants can be characterized.

For example, algorithms that integrate diverse functional, evolutionary, and DNA sequence data have shown that many human accelerated regions are developmental gene regulatory enhancers, with particular enrichment for brain activity [ 81 , 88 , 90 ]. As our understanding of how non-coding mutations influence gene expression and function improves [ 91 ], so will the accuracy and specificity of hypotheses about the effects of these regions on human-specific phenotypes.

Over the past ten years, genome-wide association studies GWAS have identified hundreds of variants associated with complex diseases [ 92 , 93 ]. These studies provide insight into the functions encoded in specific regions of the genome that can inform evolutionary questions. However, the majority of human- and population-specific variants have not been associated with functions. The recent integration of large databases of electronic health records EHRs linked to patient genotypes [ 94 ] provides a new approach to this problem. Thousands of phenotypes can be algorithmically derived from EHRs and then simultaneously tested for association with the loci of interest across thousands of individuals in a phenome-wide association study PheWAS [ 95 ].

As EHR databases grow and sequencing decreases in price, the PheWAS approach will enable efficient testing of hypotheses about the effects of mutations of evolutionary interest.

Evolution in the Post Genomic Age

Finally, new technologies, including directed stem cell differentiation, massively parallel reporter assays [ 96 ], and CRISPR gene editing [ 97 ], will facilitate faster exploration of the mechanisms driving phenotypic associations in models that closely resemble the in vivo human context. Understanding how evolutionary processes produced the human species and how developmental programs are encoded in the human genome is of great importance to basic and clinical science.

The Evolution of the Genome - Google Книги

The evolutionary history of the human genome is directly relevant to our ability to anticipate and treat human disease [ 1 ]. In this review, we have highlighted several research areas that have potential to significantly deepen our knowledge of human genome evolution over the next few years, but our list is not exhaustive. Many other areas, including the evolutionary study of human—microbe interactions [ 98 , 99 ] and experimental evolution [ ], are poised for breakthroughs.

We are also eager to see how recent technical advances in long-read genome sequencing and single cell analysis will change our understanding of evolutionary processes. Ultimately, continued analysis of the human genome in an evolutionary framework will further reveal the genetic origins of human-specific biology and improve our understanding of the etiology of human disease.

This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

National Center for Biotechnology Information , U. Curr Opin Genet Dev. Author manuscript; available in PMC Dec 1. Simonti 1 and John A. The publisher's final edited version of this article is available at Curr Opin Genet Dev. See other articles in PMC that cite the published article. Abstract Human genomes hold a record of the evolutionary forces that have shaped our species.

Introduction Understanding the evolution of the human genome is a tantalizing goal. Open in a separate window. How do gene regulatory processes influence human genome evolution? How do chemical modifications to DNA and histones constrain human genome evolution?

How should interactions between multiple genetic variants and phenotypes be modeled? What are the causes and effects of mutational biases along the human genome? What are appropriate models for the evolution and functional impact of structural variation? How can we efficiently connect human-specific genomic changes to phenotypes? Conclusion Understanding how evolutionary processes produced the human species and how developmental programs are encoded in the human genome is of great importance to basic and clinical science.

Integrating genomics into evolutionary medicine. Principles of evolutionary medicine. Oxford University Press; Fu W, Akey JM. Selection and Adaptation in the Human Genome. Annual Review of Genomics and Human Genetics. Classic selective sweeps were rare in recent human evolution. On the unfounded enthusiasm for soft selective sweeps. Great ape genetic diversity and population history.

These data revealed radical fluctuations in effective population size and genetic diversity and provide a broader context in which to interpret human evolution. Estimating the mutation load in human genomes. Bayesian inference of ancient human demography from individual genome sequences. Li H, Durbin R.

Inference of human population history from individual whole-genome sequences. Am J Hum Genet. Rare and common variants: Identification of a large set of rare complete human knockouts. Genome sequence of a 45,year-old modern human from western Siberia. It provides insights into the timing of Neanderthal interbreeding and estimates of the human mutation rate.

The complete genome sequence of a Neanderthal from the Altai Mountains. Ancient humans and the origin of modern humans.


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Evidence for archaic adaptive introgression in humans. The genomic landscape of Neanderthal ancestry in present-day humans. Vernot B, Akey JM. Genetics of human evolution: The genetics of human origins. Siepel A, Arbiza L. Cis-regulatory elements and human evolution. Evolution of transcription factor binding in metazoans [mdash] mechanisms and functional implications. Illuminating the Dark Road from Association to Function.

By comparing the sequences of individual members of a family using the techniques described in Chapter 16 it is usually possible to trace the individual gene duplications involved in evolution of the family from a single progenitor gene that existed in an ancestral genome Figure There are several mechanisms by which these gene duplications could have occurred: Unequal crossing-over is a recombination event initiated by similar nucleotide sequences that are not at identical places in a pair of homologous chromosomes.

As shown in Figure Unequal sister chromatid exchange occurs by the same mechanism as unequal crossing-over, but involves a pair of chromatids from a single chromosome see Figure DNA amplification is sometimes used in this context to describe gene duplication in bacteria and other haploid organisms Romero and Palacios, , in which duplications can arise by unequal recombination between the two daughter DNA molecules in a replication bubble Figure Replication slippage see Figure Gene duplications during the evolution of the human globin gene families.

Comparisons of their nucleotide sequences enable the evolutionary relationships between the globin genes to be deduced, using the molecular phylogenetics techniques described in more Models for gene duplication by A unequal crossing-over between homologous chromosomes, B unequal sister chromatid exchange, and C during replication of a bacterial genome. In each case, recombination occurs between two different copies of a short more The initial result of gene duplication is two identical genes.

As mentioned above with regard to genome duplication, selective constraints will ensure that one of these genes retains its original nucleotide sequence, or something very similar to it, so that it can continue to provide the protein function that was originally supplied by the single gene copy before the duplication took place.

The second copy is probably not subject to the same selective pressures and so can accumulate mutations at random. Evidence shows that the majority of new genes that arise by duplication acquire deleterious mutations that inactivate them so that they become pseudogenes Wagner, Occasionally, the mutations that accumulate within a gene copy do not lead to inactivation of the gene, but instead result in a new gene function that is useful to the organism.


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  • We have already seen that gene duplication in the globin gene families led to the evolution of new globin proteins that are used by the organism at different stages in its development see Figure 2. Further back, about million years ago, this ancestral globin gene itself arose by gene duplication, its sister duplicate evolving to give the modern gene for myoglobin, a muscle protein whose main function, like that of the globins, is the storage of oxygen Doolittle, We observe similar patterns of evolution when we compare the sequences of other genes.

    The trypsin and chymotrypsin genes, for example, are related by a common ancestor approximately million years ago Barker and Dayhoff, Both now code for proteases involved in protein breakdown in the vertebrate digestive tract, trypsin cutting other proteins at arginine and lysine amino acids and chymotrypsin cutting at phenylalanines, tryptophans and tyrosines. Genome evolution has therefore produced two complementary protein functions where originally there was just one.

    The most striking example of gene evolution by duplication, whether by duplication of a small group of genes or by whole-genome duplication, is provided by the homeotic selector genes, the key developmental genes responsible for specification of the body plans of animals. As described in Section These eight genes, as well as other homeodomain genes in Drosophila , are believed to have arisen by a series of gene duplications that began with an ancestral gene that existed about million years ago. The functions of the modern genes, each specifying the identity of a different segment of the fruit fly, gives us a tantalizing glimpse of how gene duplication and sequence divergence could, in this case, have been the underlying processes responsible for increasing the morphological complexity of the series of organisms in the Drosophila evolutionary tree.

    Vertebrates have four Hox gene clusters see Figure Not all of the vertebrate Hox genes have been ascribed functions, but we believe that the additional versions possessed by vertebrates relate to the added complexity of the vertebrate body plan. Two observations support this conclusion. The amphioxus, an invertebrate that displays some primitive vertebrate features, has two Hox clusters Brooke et al. Ray-finned fishes, probably the most diverse group of vertebrates with a vast range of different variations of the basic body plan, have seven Hox clusters Amores et al.

    Gene duplication is not always followed by sequence divergence and the evolution of a family of genes with different functions. Some multigene families are made up of genes with identical or near-identical sequences. These multiple copies of identical genes presumably reflect the need for rapid synthesis of the gene product at certain stages of the cell cycle. With these gene families there must be a mechanism that prevents the individual copies from accumulating mutations and hence diverging away from the functional sequence.

    This is called concerted evolution. If one copy of the family acquires an advantageous mutation then it is possible for that mutation to spread throughout the family until all members possess it. The most likely way in which this can be achieved is by gene conversion which, as described in Section Multiple gene conversion events could therefore maintain identity among the sequences of the individual members of a multigene family. Gene duplication and genetic redundancy. The text adopts the conventional scenario which states that after a duplication, one of the two gene copies can accumulate mutations which either result in inactivation of that gene copy or lead to a new gene function.

    As well as the generation of new genes by duplication followed by mutation, novel protein functions can also be produced by rearranging existing genes. This is possible because most proteins are made up of structural domains Section 3. There are two ways in which rearrangement of domain-encoding gene segments can result in novel protein functions. Structural domains are individual units in a polypeptide chain coded by a contiguous series of nucleotides.

    In this simplified example, each secondary structure in the polypeptide is looked upon as an individual structural domain. In reality, most structural more Creating new genes by A domain duplication and B domain shuffling. Implicit in these models of domain duplication and shuffling is the need for the relevant gene segments to be separated so that they can themselves be rearranged and shuffled.

    This requirement has led to the attractive suggestion that exons might code for structural domains. With some proteins, duplication or shuffling of exons does seem to have resulted in the structures seen today. Each of the three collagen polypeptides has a highly repetitive sequence made up of repeats of the tripeptide glycine-X- Y , where X is usually proline and Y is usually hydroxyproline Figure Within this region, each exon encodes a set of complete tripeptide repeats.

    The number of repeats per exon varies but is 5 5 exons , 6 23 exons , 11 5 exons , 12 8 exons or 18 1 exon. Clearly this gene could have evolved by duplication of exons leading to repetition of the structural domains. Every third amino acid is glycine, X is often proline and Y is often hydroxyproline Hyp. Hydroxyproline is a more Domain shuffling is illustrated by tissue plasminogen activator TPA , a protein found in the blood of vertebrates and which is involved in the blood clotting response.

    The TPA gene has four exons, each coding for a different structural domain Figure This exon appears to be derived from a second fibrin-binding protein, fibronectin, and is absent from the gene for a related protein, urokinase, which is not activated by fibrin. The second TPA exon specifies a growth-factor domain which has apparently been obtained from the gene for epidermal growth factor and which may enable TPA to stimulate cell proliferation.

    The modular structure of the tissue plasminogen activator protein. See the text for details. Type I collagen and TPA provide elegant examples of gene evolution but, unfortunately, the clear links that they display between structural domains and exons are exceptional and are rarely seen with other genes.

    Many other genes appear to have evolved by duplication and shuffling of segments, but in these the structural domains are coded by segments of genes that do not coincide with individual exons or even groups of exons. Domain duplication and shuffling still occur, but presumably in a less precise manner and with many of the rearranged genes having no useful function.

    Despite being haphazard, the process clearly works, as indicated by, among other examples, the number of proteins that share the same DNA -binding motifs Section 9. Several of these motifs probably evolved de novo on more than one occasion, but it is clear that in many cases the nucleotide sequence coding for the motif has been transferred to a variety of different genes. The second possible way in which a genome can acquire new genes is to obtain them from another species. Comparisons of bacterial and archaeal genome sequences suggest that lateral gene transfer has been a major event in the evolution of prokaryotic genomes Section 2.

    The genomes of most bacteria and archaea contain at least a few hundred kb of DNA , representing tens of genes, that appears to have been acquired from a second prokaryote. There are several mechanisms by which genes can be transferred between prokaryotes but it is difficult to be sure how important these various processes have been in shaping the genomes of these organisms.

    On a day-to-day basis, plasmid transfer is important because it is the means by which genes for resistance to antibiotics such as chloramphenicol, kanamycin and streptomycin spread through bacterial populations and across species barriers, but its evolutionary relevance is questionable. It is true that the genes transferred by conjugation can become integrated into the recipient bacterium's genome, but usually the genes are carried by composite transposons see Figure 2. A second process for DNA transfer between prokaryotes, transformation Section 5. Only a few bacteria, notably members of the Bacillus , Pseudomonas and Streptococcus genera, have efficient mechanisms for the uptake of DNA from the surrounding environment, but efficiency of DNA uptake is probably not relevant when we are dealing with an evolutionary time-scale.

    More important is the fact that gene flow by transformation can occur between any pair of prokaryotes, not just closely related ones as is the case with conjugation , and so could account for the transfers that appear to have occurred between bacterial and archaeal genomes Section 2. In plants, new genes can be acquired by polyploidization. We have already seen how autopolyploidization can result in genome duplication in plants see Figure Allopolyploidy , which results from interbreeding between two different species, is also common and, like autopolyploidy, can result in a viable hybrid.

    Usually, the two species that form the allopolyploid are closely related and have many genes in common, but each parent will possess a few novel genes or at least distinctive alleles of shared genes. For example, the bread wheat, Triticum aestivum , is a hexaploid that arose by allopolyploidization between cultivated emmer wheat, T. The wild-grass nucleus contained novel alleles for the high-molecular-weight glutenin genes which, when combined with the glutenin alleles already present in emmer wheat, resulted in the superior properties for breadmaking displayed by the hexaploid wheats.

    Allopolyploidization can therefore be looked upon as a combination of genome duplication and interspecies gene transfer. Among animals, the species barriers are less easy to cross and it is difficult to find clear evidence for lateral gene transfer of any kind. Several eukaryotic genes have features associated with archaeal or bacterial sequences, but rather than being the result of lateral gene transfer, these similarities are thought to result from conservation during millions of years of parallel evolution.

    Most proposals for gene transfer between animal species center on retroviruses and transposable elements. Transfer of retroviruses between animal species is well documented, as is their ability to carry animal genes between individuals of the same species, suggesting that they might be possible mediators of lateral gene transfer. The same could be true of transposable elements such as P elements, which are known to spread from one Drosophila species to another, and mariner , which has also been shown to transfer between Drosophila species and which may have crossed from other species into humans Robertson et al.

    So far we have concentrated our attention on the evolution of the coding component of the genome. As coding DNA makes up only 1. The problem is that in many respects there is little that can be said about the evolution of non-coding DNA. We envisage that duplications and other rearrangements have occurred through recombination and replication slippage, and that sequences have diverged through accumulation of mutations unfettered by the restraining selective forces acting on functional regions of the genome.

    We recognize that some parts of the non-coding DNA, for example the regulatory regions upstream of genes, have important functions, but as far as most of the non-coding DNA is concerned, all we can say is that it evolves in an apparently random fashion. This randomness does not apply to all components of the non-coding DNA.

    In particular, transposable elements and introns have interesting evolutionary histories and are of general importance in genome evolution, as described in the following two sections. Transposable elements have a number of effects on evolution of the genome as a whole. The most significant of these is the ability of transposons to initiate recombination events that lead to genome rearrangements.

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    This has nothing to do with the transposable activity of these elements, it simply relates to the fact that different copies of the same element have similar sequences and can therefore initiate recombination between two parts of the same chromosome or between different chromosomes Figure In many cases, the resulting rearrangement will be harmful because important genes will be deleted, but some instances where the result has been beneficial have been documented.

    Transposons can initiate recombination events between chromosomes or between different sites on the same chromosome. Movement of transposons from one site to another can also have an impact on genome evolution. Transposition has also been associated with altered patterns of gene expression. For example, the efficiency with which DNA-binding proteins that are attached to upstream regulatory sequences can activate transcription of a gene might be affected if a transposon moves into a new site immediately upstream of the gene Figure An interesting example of transposon-directed gene expression occurs with the mouse gene Slp , which codes for a protein involved in the immune response, the tissue specificity of Slp being conferred by an enhancer located within an adjacent retrotransposon Stavenhagen and Robins, There are also examples where insertion of a transposon into a gene has resulted in an altered splicing pattern Purugganan and Wessler, Insertion of a transposon into the region upstream of a gene could affect the ability of DNA-binding proteins to activate transcription.

    The origin of a microsatellite. There is no mystery about the origins of microsatellite repeat sequences Section 2. A dimeric microsatellite, consisting of two repeat units in tandem array, can easily arise by chance mutational events. Ever since introns were first discovered in the s their origins have been debated. The problems surround the origins of the GU-AG introns, the ones that are found in large numbers in eukaryotic nuclear genomes. A number of proposals for the origins of GU-AG introns have been put forward but the debate is generally considered to be between two opposing hypotheses: There are several different models for each hypothesis.

    These genomes would have contained many short genes, each derived from a single coding RNA molecule and each specifying a very small polypeptide, perhaps just a single structural domain. These polypeptides would probably have had to associate together into larger multidomain proteins in order to produce enzymes with specific and efficient catalytic mechanisms Figure To aid the synthesis of a multidomain enzyme it would have been beneficial for the enzyme's individual polypeptides to become linked into a single protein, such as we see today.

    This was achieved by splicing together the transcripts of the relevant minigenes, a process that was aided by rearranging the genome so that groups of minigenes specifying the different parts of individual multidomain proteins were positioned next to each other. In other words, the minigenes became exons and the DNA sequences between them became introns.

    The short genes of the first genomes probably coded for single-domain polypeptides that would have had to associate together to form a multisubunit protein to produce an effective enzyme. Later the synthesis more But we know that bacterial genomes do not have GU-AG introns, so if these hypotheses are correct then we must assume that for some reason introns became lost from the ancestral bacterial genome at an early stage in its evolution.

    This is a stumbling block because it is difficult to envisage how a large number of introns could be lost from a genome without risking the disruption of many gene functions. If an intron is removed from a gene with any imprecision then a part of the coding region will be lost or a frameshift mutation will occur, both of which would be expected to inactivate the gene.

    One of the reasons why the debate regarding the origin of GU-AG introns has continued for over 20 years is because evidence in support of either hypothesis has been difficult to obtain and is often ambiguous. However, when a larger number of species was examined the positions of the introns in this gene became less easy to interpret: Intron numbers must therefore have increased by recombination events, which is possible with both hypotheses. A study of vertebrate globin proteins concluded that each of these comprises four structural domains, the first corresponding to exon 1 of the globin gene, the second and third to exon 2, and the fourth to exon 3 Figure The prediction that there should be globin genes with another intron that splits the second and third domains was found to be correct when the leghemoglobin gene of soybean was shown to have an intron at exactly the expected position Jensen et al.

    Unfortunately, as more globin genes were sequenced more introns were discovered - more than ten in all. The positions of the majority of these do not correspond to junctions between domains. A vertebrate globin gene showing the relationship between the three exons and the four domains of the globin protein. The globin genes therefore conform with the general principle that emerged from our discussion of domain shuffling Section A more subtle interpretation might be that a structural domain is a polypeptide segment whose amino acids are less than a certain distance apart in the protein's tertiary structure.

    It has been suggested that when this definition is adopted there is a better correlation between structural domain and exon de Souza et al.

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    The role of non-coding DNA. The presence of extensive amounts of non-coding DNA in eukaryotic genomes see Box 1. Why is this apparently superfluous DNA tolerated? One possibility is that the non-coding DNA has more Although the evolutionary history of humans is controversial, it is generally accepted that our closest relative among the primates is the chimpanzee and that the most recent ancestor that we share with the chimps lived 4.

    Since the split, the human lineage has embraced two genera - Australopithecus and Homo - and a number of species, not all of which were on the direct line of descent to Homo sapiens Figure The result is us, a novel species in possession of what are, at least to our eyes, important biological attributes that make us very different from all other animals. So how different are we from the chimpanzees? One possible scheme for the evolution of modern humans from australopithecine ancestors. There are many controversies in this area of research and several different hypotheses have been proposed for the evolutionary relationships between different fossils.

    Within the coding DNA the difference is less than 1. Only a few clear differences have been discovered: Humans lack a bp segment of the gene for the N -glycolyl-neuraminic acid hydroxylase and so cannot synthesize the hydroxylated form of N -glycolyl-neuraminic acid, which is present on the surfaces of some chimpanzee cells Chou et al. This may have an effect on the ability of certain pathogens to enter human cells, and could possibly influence some types of cell-cell interaction, but the difference is not thought to be particularly significant.

    Several recent gene duplications have occurred, resulting in gene copies that can be described as human-specific or chimpanzee-specific, as they are present in only one or the other genome. However, as far as gene functions are concerned these new genes are not significant because they have not yet had time to accumulate mutations to any great extent and so, in effect, are simply second copies of the genes from which they were derived. Some components of the non-coding DNA in the two genomes have diverged extensively, illustrating how quickly repetitive DNA can evolve. For example, the alphoid DNA sequences present at human centromeres Section 2.

    The human genome also contains novel versions of the Alu element Section 2. Human and chimpanzee genomes have undergone a few rearrangements, as revealed when the chromosome banding patterns are compared. The most dramatic difference is that human chromosome 2 is two separate chromosomes in chimpanzees Figure Four other chromosomes - human numbers 5, 6, 9 and 12 - also have visible differences to their chimpanzee counterparts, although the other 18 chromosomes appear to be very similar if not identical Yunis and Prakash, Human chromosome 2 is the product of a fusion between two chimpanzee chromosomes.

    For more details about the banding patterns of these chromosomes, from which the fusion is deduced, see Strachan and Read These differences are interesting as far as genome evolution is concerned but none of them reveals anything about the basis of the special biological attributes possessed by humans. This question - what makes us different from chimpanzees and other apes - is perplexing molecular biologists, who have been frustrated by the absence of a sequencing project for any of the ape genomes Gibbons, But this is only part of the problem because many of the key differences between humans and apes are likely to lie with subtle changes in the expression patterns of genes involved in developmental processes and in specification of interconnections within the nervous system.

    Differences in the expression patterns of genes in the brains of humans and chimps have been revealed by microarray analysis see Technical Note 5. It is clear, however, that what makes us human is probably not the human genome itself, but the way in which the genome functions. Give short definitions of the following terms: Summarize current thinking regarding the processes that led to evolution of the first genomes. Be careful to distinguish between the RNA world and the DNA world and to indicate how the transition from the former to latter is thought to have occurred.

    Which periods during the last 1. Describe how the formation of an autopolyploid could result in an increase in gene number. What indications are there that genome duplication has been important during the evolutionary histories of present-day genomes? Using diagrams, distinguish between the four processes that could lead to gene duplication. Explain how the globin gene superfamily illustrates the importance of gene duplication in genome evolution. Discuss the impact of gene duplication on the evolution of the homeotic selector genes of eukaryotes.

    Describe, with examples, the processes of domain duplication and domain shuffling. Discuss the evidence for lateral gene transfer between prokaryotic organisms. To what extent is lateral gene transfer likely to have contributed to genome evolution in eukaryotes? Outline the impact that transposable elements can have on genome evolution.

    What evidence is there to support these hypotheses? List the ways in which the human genome differs from that of chimpanzees. What are the likely genetic explanations for the important differences between the biological attributes of humans and chimps? Are the examples of domain duplication and domain shuffling given in Section Indeed, one of the publications describing the draft human genome sequence lists 31 human genes that might have been acquired from bacteria by lateral gene transfer IHGSC [International Human Genome Sequencing Consortium] [] Initial sequencing and analysis of the human genome.

    Nature , , — Explore the controversies surrounding the influence of lateral gene transfer on the composition of the human genome. Examine the differences between the human and chimpanzee genomes and provide a more detailed account of the reasons for the biological differences between humans and chimps. Turn recording back on. National Center for Biotechnology Information , U. Show details Brown TA. Contents Current edition published by Garland Science.

    Chapter 15 How Genomes Evolve. Learning outcomes When you have read Chapter 15 , you should be able to: Speculate on the events that led to evolution of the first genomes. Using examples, discuss the possible impacts that duplication of whole genomes and of individual genes or groups of genes has had on genome evolution.

    Assess the likely impact of lateral gene transfer on genome evolution in bacteria and in eukaryotes. List the differences between the human and chimpanzee genomes and discuss how such similar genomes can give rise to such different biological attributes. The origins of genomes The first oceans are thought to have had a similar salt composition to those of today but the Earth's atmosphere, and hence the dissolved gases in the oceans, was very different.

    The first biochemical systems were centered on RNA Polymerization of the building blocks into biomolecules might have occurred in the oceans or could have been promoted by the repeated condensation and drying of droplets of water in clouds Woese, Synthesis of peptide bonds, by the rRNA component of the ribosome Section How unique is life?

    Acquisition of New Genes Although the very old fossil record is difficult to interpret, there is reasonably convincing evidence that by 3. Acquisition of new genes by gene duplication The duplication of existing genes is almost certainly the most important process for the generation of new genes during genome evolution.