Can mitochondria go through a horizontal gene transfer


Both neutral and selective evolutionary processes can be read from genomes

As you have learned in Sect. 10.1007 / 978-3-662-58172-8_12 # Sec12, a mutation is understood to mean any change in the genetic material. One form of mutation that can establish itself in a population is the point mutation, the exchange of a single nucleotide. Many such nucleotide substitutions in DNA have no effect on a protein - not even if the change is made to a protein-coding gene, because there is more than one codon for most amino acids (Fig. 10.1007 / 978-3-662-58172- 8_14 # Fig4). A substitution that does not lead to another amino acid is known as synonyms , neutral or silent substitution (Fig.23.4a). Synonyms substitutions have no effect on the structure and function of a protein (but can have other effects, as described in Sect. 10.1007 / 978-3-662-58172-8_15 # Sec1) and are therefore probably less subject to the influence of natural selection than others Forms of substitution.

In a nutshell

  • Neutral evolution differs from negative (cleansing) and positive selection in that it does not affect the survivability and reproduction of the organism in question.

  • The rate of fixation of neutral nucleotide substitutions within populations is independent of population size.

  • By comparing the rates of synonymous and nonsynonymous substitutions, one can see positive and negative selection in protein genes.

  • The genomes of organisms are characterized by very different sizes, but the number of protein-coding genes is much less variable.

Cross reference

The genetic code determines which codon codes which amino acid (Fig. 10.1007 / 978-3-662-58172-8_14 # Fig4).

A nucleotide substitution that leads to a change in the amino acid sequence encoded by a gene is called a non-synonymous substitution (Fig. 23.4 b). A distinction is made between such substitutions Missense substitutionsthat lead to a change in the amino acid concerned, and Nonsense substitutionsresulting in a stop codon and thus a chain termination. In general, non-synonymous substitutions tend to be detrimental to the organism. But not every amino acid exchange also changes the shape and charge of a protein (and thus influences its functional properties), so that non-synonymous substitutions can also be completely (or almost) neutral and are therefore not read out by the selection. Conversely, an amino acid exchange that gives the organism an advantage will lead to a positive selection for the corresponding non-synonymous substitution.

For some highly conserved protein-coding genes, scientists have determined the rate of nonsynonymous nucleotide substitutions: It is around 0.9 substitutions per position per billion years. Synonymous substitutions are about five times more common in these genes than non-synonymous. In other words, the substitution rates are highest at those nucleotide positions that do not lead to any change in the expressed amino acid (Fig. 23.5). The substitution rate is even higher in the case of pseudogenes, i.e. in the case of gene copies created by duplication that no longer fulfill their function and are therefore not subject to selection.

Most natural populations of organisms exhibit more genetic variability than would be expected if that variability were mainly influenced by natural selection. This finding, together with the knowledge that many mutations do not change the function of proteins, led to the development of the neutral theory of molecular evolution.

Evolution is largely neutral

In 1968 the Japanese Motoo Kimura formulated the Neutral theory of molecular evolution. According to Kimura's hypothesis, which has now been established as a theory, the majority of the variants observed in most populations are neutral with regard to selection at the molecular level - that is, they are neither advantageous nor disadvantageous for their carriers. Therefore, these neutral variants tend to accumulate through genetic drift rather than through positive selection.

The fixation rate of neutral mutation through gene drift is independent of the population size. To make it clear why this is so, a population of the same size is used here with a rate of neutral mutations at a gene location of per gamet and generation. In this case, the number of new mutations would be on average 2, because gene copies are available for mutations. The probability that a particular mutation is fixed by genetic drift alone is equal to its frequency; this is the same for a newly created mutation. Then multiplying these two terms gives you the fixation rate of neutral mutations in a given population of individuals:

Thus, the fixation rate of neutral mutations depends only on the rate of neutral mutations and is independent of the population size. A particular mutation is more likely to appear in a large population than a small population, but in a small population, any mutation that appears is more likely to be fixed. These two effects of population size cancel each other out. Thus, the rate of fixation of neutral mutations is equal to the rate of mutation (i.e.,).

As long as the underlying mutation rate is constant, macromolecules that arise in different populations should therefore develop apart at a constant rate through neutral changes. As research has confirmed, the rate of evolution of certain genes and proteins actually remains relatively constant over time and can therefore serve as a “molecular clock”. As you have learned in Sect. 10.1007 / 978-3-662-58172-8_21 # Sec11, one can use molecular clocks to calculate the point in time at which splitting of species occurred.

Even though much of the genetic variability observed in populations is the result of neutral evolution, the neutral theory does not say that most mutations do not affect the organism. Many mutations are not even noticed in populations because they are lethal or very disadvantageous for the organisms and are therefore quickly eliminated from the population by natural selection. Similarly, mutations that offer a selection advantage are usually fixed quickly in populations and therefore also do not lead to variability at the population level. Nevertheless, in all populations, some amino acid positions remain constant under negative (cleansing) selection, others vary due to neutral genetic drift, and still others will be different due to positive selection for change. How can these evolutionary processes be distinguished?

Experiment: Convergent Molecular Evolution

Looking at the data: convergent molecular evolution

Experiment: Convergent Molecular Evolution

Original literature : Stewart C-B et al. (1987) Nature 330: 401–404

Langurs (a monkey family) and cattle are only distantly related, but both have special fermentation chambers for plant food in the front section of their digestive tract. Only they express the enzyme lysozyme in this fermentation chamber, which helps them break down the bacteria involved in fermentation. Stewart and her colleagues compared the gene sequences of lysozyme in mammals with and without such a fermentation chamber, because they wanted to find out whether a convergence could be observed between the independently evolved amino acid sequences of the lysozyme in langurs and cattle.


In adapting to fermentation chamber digestion, similar selection conditions in distantly related mammals have resulted in convergence in the amino acid sequences of lysozyme.


  1. Lysozyme was isolated from two distantly related mammal species with a fermentation chamber for digestion (langurs and cattle) and some other mammals that are closely related to either langurs or cattle but do not have such a fermentation chamber and then sequenced.

  2. The differences in the amino acid sequences were entered in pairs in a table. The amino acid changes were then entered in the evolutionary family tree and the number of convergent similarities between each of the species pairs was determined. The results can then be displayed as a distance matrix.


The matrix shows the number of amino acid differences for each species pair above the diagonal and the number of convergent similarities below.


The majority of the convergent similarities between the individual pairs of species can be demonstrated in the lysozyme sequences of the two species with a fermentation chamber for digestion; At the same time, a molecular convergence emerges along with the independent evolution of a fermentation chamber for digestion.

Looking at the data: convergent molecular evolution

Caro-Beth Stewart and her team determined lysozyme sequences from six different mammalian species. The table shows a small part of their data. The family tree of these six species shown here is very well secured due to the analysis of many genes and numerous morphological data.


  1. Using the family tree in Experiment: Convergent Molecular Evolution, record the amino acid differences in the phylogenetic history of the six mammalian species. Assume that the amino acid at the base of the family tree is the starting point.

  2. Which amino acid positions show a particular convergence between the lines of langurs and cattle (i.e. the derived state is found exclusively in cattle and langurs)?

  3. What additional position is convergent in cattle and the ancestor of langurs and baboons?

  4. Have you seen any more convergent amino acid changes between two other lines? What does this say about the convergent changes you've seen between cattle and langurs?

Amino acid position
original conditionVR.M.R.QW.ND.KNV

Positive and negative selection can be detected in the genome

As you have just learned, when it comes to the base exchanges in a protein-coding gene, a distinction can be made between synonymous and nonsynonymous substitutions, depending on whether or not they lead to a change in the amino acid sequence of the resulting protein. It is to be expected that the relative rate of synonymous and nonsynonymous substitutions will be different in gene segments that evolve neutrally or are subject to positive selection for change; under negative selection it will remain unchanged.

  • If there are several alternatives for a certain amino acid in a protein (without changing the protein function), then such an exchange affects the biological fitness of an organism neutral out. In this case, it is to be expected that the rates of synonymous and nonsynonymous substitutions in the corresponding DNA sequence will be very similar, so that the ratio of the two rates is close to 1.

  • A certain amino acid position is subject to a positiveselection for changes, it can be assumed that the rate of non-synonymous substitutions exceeds the rate of synonymous substitutions in the corresponding DNA sequences.

  • A certain amino acid position is subject to a negative selection (or purifying selection), then the observed rate of synonymous substitutions n will be very much higher than the rate of nonsynonymous substitutions in the corresponding DNA sequences.

By comparing the gene sequences that encode homologous proteins from many species, scientists can understand the genesis and timing of synonymous and nonsynonymous substitutions. This information can then, as described in Chap. 10.1007 / 978-3-662-58172-8_21, can be entered in an evolutionary family tree (phylogenetic tree). One can identify gene segments that develop under neutral, negative or positive selection by comparing the form of the substitutions and the substitution rates in such a family tree.

By researching the genome sequences of synonymous and non-synonymous substitutions, biologists have found out which amino acid positions of the surface proteins of influenza viruses evolve under positive selection (and thus escape the immune recognition of their host organisms). With this information, scientists can find out which of the viruses in current flu epidemics are most likely not to be recognized by the human immune system. These viruses are very likely to cause the next flu epidemic and are therefore the best candidates for vaccine production. As explained in the introduction to this chapter (“The fascination of research: The theory of evolution contributes to the development of better flu vaccines”), the effects could of the flu epidemics in the past few decades will be greatly reduced by producing effective flu vaccines.

A study on the evolution of lysozyme shows how and why certain amino acid positions are subject to different forms of selection ("Experiment: Convergent Molecular Evolution"). The enzyme lysozyme (Fig. 10.1007 / 978-3-662-58172-8_3 # Fig9) occurs in almost all animals. It is part of the tear fluid, saliva and milk of mammals as well as the albumen of bird eggs. Lysozyme can break down certain components of the bacterial cell wall and thus damage and kill the bacteria. As a result, it plays an important role as the first line of defense against bacterial infections. Most animals fight bacteria by digesting them; this is also the reason why most animals have lysozyme as a defense protein. However, some animals also use lysozyme to digest their food.

A form of digestion has developed twice within mammals in which the fermentation of the food takes place in a fermentation chamber in the front area of ​​the digestive tract. In this mode of digestion, parts of the anterior alimentary canal - the back section of the esophagus or stomach - have been converted into a fermentation chamber, in which bacteria ferment the ingested plant matter. Animals with such a fermentation chamber can also utilize the otherwise indigestible cellulose, of which plant tissue largely consists (because bacteria break down the cellulose to glucose and thereby grow and the animals then digest the excess of bacteria). This form of fermentation chamber digestion developed independently of each other in ruminants (a group of ungulates that includes cattle) and in certain leaf-eating monkeys such as langurs. It was clear that these developments took place independently of one another, because both langurs and ruminants have relatively close relatives who do not have such fermentation chambers for digestion.

In both lines of development with a fermentation chamber for digestion, lysozyme was modified in such a way that it no longer only serves as a defense and now has a new role. This lysozyme destroys the cell wall of some of the bacteria that live in the fermentation chamber, releasing their nutrients, which the mammals then digest. How many changes to the lysozyme molecule did it take to perform its new function amid the digestive enzymes and acidic conditions in the fermentation chamber of these mammals? To answer this question, Stewart and co-workers compared the lysozyme-coding sequences of mammals with a fermentation chamber to those of some of their relatives who do not have such a chamber. In doing so, they determined which amino acids are different and which are common to each species, as well as the rates of synonymous and nonsynonymous substitutions in the lysozyme genes over the course of the phylogenetic history of the species examined.

For many of the amino acid positions of lysozyme, the rate of synonymous substitutions in the corresponding gene sequence was significantly higher than the rate of nonsynonymous substitutions. This observation suggests that many of the amino acids that make up lysozyme evolve when exposed to negative selection. In other words, there is a selection against a change in the protein at these positions. Therefore, the amino acids in question must be crucial for the function of lysozyme. Several different amino acids work equally well in other positions; the corresponding gene sequences were characterized by similar rates of synonymous and nonsynonymous substitutions.Most astonishing, however, was the observation that in the line leading to the langurs, amino acid exchanges in the lysozyme had taken place at a much higher rate than in all other primate lines. The high rate of nonsynonymous substitutions in the lysozyme gene of langurs shows that lysozyme underwent a period of rapid change in adapting to the specific digestive tract of langurs. In addition, the lysozymes of langurs and cattle are each characterized by five common, unique amino acid exchanges. All of these amino acids are located on the surface of the lysozyme molecule, far from its active center. In two of these joint exchanges, lysine replaced an arginine in each case. This makes the proteins more resistant to attacks by the gastric enzyme pepsin. By understanding the functional significance of the amino acid exchanges, scientists can explain the observed changes in the amino acid sequences with the functional change of the protein.

Numerous fossil records, morphological findings, and molecular data show that langurs and ruminants did not have a common ancestor in recent times. However, the lysozymes of langurs and ruminants have several amino acids in common, none of which are found in any of the close relatives of these two mammals. Despite the different origins of the two groups of mammals, their lysozymes have undergone a convergent evolution at some amino acid positions. The amino acids common to both animal groups give these special lysozymes the ability to break down bacteria even under the environmental conditions prevailing in the fermentation chamber.

Another notable example of the convergent evolution of lysozyme is provided by the hoatzins, also known as crested chickens. These unusual leaf-eating birds from South America are the only known birds with a fermentation chamber for digestion. Although many birds have a bulge in the esophagus known as a goiter, it is only in Hoatzins that the goiter contains lysozyme and bacteria and acts as a fermentation chamber. Many of the amino acid exchanges that occurred in the course of the adaptation of the lysozyme in the hoatzin's crop are identical to those that occurred in ruminants and langurs. So, although the hoatzins and fermentation chamber mammals had no common ancestor for the past few hundred million years, they have developed similar adaptations of their lysozyme that allow them to deprive their fermentation bacteria of nutrients.

The size of the genome also evolves

It is well known that there are considerable differences in the size of the genomes in different organisms. If one looks at the large taxonomic categories, a certain correlation between the size of the genome and the complexity of the organisms can be seen. The genome of the tiny bacterium Mycoplasma genitalium includes only 470 genes. The genome of the bacterium consists of 634 genes Rickettsia prowazekii , the causative agent of typhus. However, owns homo sapiens approximately 21,000 protein coding genes. Fig. 23.6 shows the number of genes in a selection of organisms whose genomes have already been completely sequenced, arranged according to their known evolutionary relationships. As you can see from the figure, a larger genome does not mean a higher phenotype complexity. (Compare rice with the other plants, for example.) Not surprisingly, a large, multicellular organism requires more and more complex genetic information to build and function than a small, unicellular bacterium. It is surprising, however, that some organisms, such as lung fish, some tailed amphibians and lilies, have around 40 times more DNA in their cell nucleus than humans, for example. Of course, a lungfish or a lily is not 40 times more complex than a human. Then why does the genome size vary so much?

The differences in genome size are not that great if one only looks at the portion of DNA that actually encodes proteins or defines sequences of RNAs other than mRNAs. The organisms with the largest amount of nuclear DNA (some ferns and flowering plants) have 80,000 times as much DNA as the bacteria with the smallest genomes, but none of the species has more than 100 times as many protein-coding genes as a bacterium . Therefore, most of the differences in genome size are not based on the number of functional genes, but on the amount of non-coding DNA (Fig. 23.7).

Why do the cells of most eukaryotic organisms contain so much non-coding DNA? As mentioned earlier, some of the non-coding DNA has a regulatory function and controls the extent or timing of the expression of coding genes. However, the genomes of many species contain far more non-coding DNA than is required for gene regulation. Does this additional non-coding DNA have any function or is it completely useless (in the past it was often referred to as junk DNA)? Many sections of non-coding DNA consist of pseudogenes (that is, functionless copies of former genes) that simply remain in the genome because the effort involved is so negligible. These pseudogenes can become the starting material for the evolution of new genes with new functions. Some of the non-coding DNA only helps maintain the structure of the chromosomes. Other sequences are "selfish" transposable elements that spread rapidly because they reproduce faster than the host genome.

Over time, not only does DNA accumulate in genomes, but unimportant nucleotide sequences are also lost from them. Some species also have genomes of so different sizes because the insignificant sequences are eliminated at very different rates. Using retrotransposons, scientists can estimate the rate at which species are losing DNA. Retrotransposons are transposable elements (Fig. 10.1007 / 978-3-662-58172-8_17 # Fig4) that copy themselves via an intermediate RNA stage. The most common form of retrotransposons has duplicated sequences at each end, which are called long terminal repeats (long terminal repeats, LTRs). Occasionally there is a recombination of the LTRs in the host genome in such a way that the DNA in between is cut out. When that happens, a recombined LTR is left behind. The number of such “orphaned” LTRs in a genome is a measure of how many retrotransposons have been lost. By comparing the number of LTRs in the genome of Hawaiian crickets of the genus Laupala and in that of fruit flies (Drosophila) researchers found that Laupala 40 times slower to lose DNA than Drosophila. It is therefore not surprising that the genome of Laupala is much larger than that of Drosophila.