Ofer Mokidi, Tel Aviv University
The genetic difference between humans and chimpanzees is "only" 1.2%. And if that is not enough, part of this difference is neutral and does not manifest itself. Now, for the first time, the genetic changes that may have enabled the unique development of man have been identified. At the top of the list are changes related to taste and smell
What makes a creature human? This question can be asked on the philosophical level, but it can also be asked on the biological level. That is, what physiological, anatomical and behavioral features make us human?
To begin to answer this question it is necessary to compare the person with his "relatives". The hypothesis of man's evolutionary closeness to the African apes (chimpanzee and gorilla, for example), put forward in 1863 by the biologist Thomas Henry Huxley, has been the basis of research efforts ever since. Structural details, such as certain muscles that enable the thumb movement unique to humans, as well as immunological similarities between certain blood proteins, were examined to determine which species is the closest to humans. Most of the collected data points to the chimpanzee as the closest living creature to us today.
Information accumulated in recent years about the human genome and the genome of the chimpanzee makes the question of the closeness of the human and the chimpanzee confusing: the degree of similarity between the DNA of the two species is close to 99%. Moreover, there is no reason to assume that the small difference that was nevertheless discovered in the DNA sequences (1.2%) necessarily represents significant unique human traits. This is because genetic differences between separate evolutionary lines (in this case, the line that led to chimpanzees and the line that led to man, which diverged from each other about 5 million years ago) also arise regardless of specific traits that confer advantages.
The force due to which random genetic differences are preserved, distinguishing any two evolutionary lines without any relation to advantages or disadvantages, is called "genetic drift". The reference to the impressive power of genetic drift led to the development of the neutralist approach in the study of evolution in the mid-70s. This approach holds that most differences in DNA sequences between different species are neutral. According to what is known today, large parts of DNA are not coded (that is, they do not dictate properties; they are not genes), and in these parts it can be expected that many of the differences between two genomes will be neutral. However, even in DNA segments that encode biological traits, differences between genomes can be neutral. That is, even the same 1.2% difference in DNA almost necessarily also includes differences that do not confer any advantage or disadvantage but have been preserved due to genetic drift.
These differences will not make it possible to characterize genes that "thanks" to us being human. In order to do this, it is necessary to focus on the differences in the DNA sequence that were created as a result of different regimes of natural selection (selection) in the evolutionary lines of man and chimpanzee. This was the purpose of a study recently published in the journal "Science" by a group of researchers led by Andrew Clark from Cornell University and Michelle Cargill from "Clera", a company that played a central role in the human genome project.
The researchers used large knowledge bases accumulated on human, chimpanzee and mouse DNA sequences. The database included more than 7,500 genes for which there are sequences from all three animals, and for which the degree of similarity between them is sufficient to assume that they represent genes that evolved from a common origin (homologous genes). Adding the mouse to the study is extremely important. It is assumed that the human and the chimpanzee share a common ancestor with them and not with the mouse; Therefore, the mouse can be used as a reference point outside the group under consideration - the human and the chimpanzee. This form of analysis allows, subject to certain assumptions and models and by means of appropriate computer programs, to reconstruct the DNA sequences of the human and chimpanzee ancestor. Given these sequences, it is possible to distinguish between changes that occurred since that ancestor in the branch that led to man and those that occurred in the branch that led to the chimpanzee.
Only some of the changes caused by random factors at the DNA level - mutations - are those that will also result in a change in proteins, which are the ones that shape to a great extent the variety of properties of biological beings. The researchers chose to deal with these changes. To focus on the differences that most likely reflect different regimes of natural selection that operated along the evolutionary line of man and the chimpanzee, the researchers used models that distinguish between differences in DNA that will lead to a change in the protein and differences that will not lead to such a change. Differences in the DNA that are not reflected in the protein (results of so-called "silent mutations") are a measure of the frequency with which mutations damage a certain region of the DNA; A kind of "background noise" of neutral changes that have no meaning in terms of the operation of natural selection. Therefore, these differences can serve as a reference point for examining the important question: Did changes occur in a certain gene that resulted in a change in the protein at a higher or lower rate than the "background" rate?
The researchers were interested in locating genes in which positive selection was operating, i.e. genes whose changes conferred an advantage throughout evolution in the branch that led to man. To this end, they focused on the genes where the following special pattern of differences exists: the DNA sequence differences that result in a change in the protein are more than those that do not result in a change in the protein, meaning that the rate of significant mutations is higher than the background rate. Such a model is expected to be rare: a fundamental working assumption in evolution studies holds that most mutations will be for the worse - if the biological mechanisms of a certain creature work well, and the evidence for this is that this creature exists in its environment, most of the random changes that can be introduced in these mechanisms are likely to be harmful, and only some of them will be beneficial.
About 1,500 human genes, and a similar number of chimpanzee genes, displayed a pattern of differences indicative of positive selection. Then the researchers performed the most fascinating analysis. They used a statistical model that located genes that had undergone positive selection in the branch leading to man only. 125 gardens did present this unique model. If we take a far-reaching interpretation, these are genes whose changes in the proteins they encode may have been "required" in the evolutionary process that led to the creation of man.
Well, which genes are these? What are the proteins and what are the biological properties and processes that "make" a person? At the top of the list, ranked according to the degree of statistical significance, are genes that encode various components of our sensory systems. This group includes, among others, specific receptors and intracellular communication pathways. Perhaps surprisingly, components of chemical sensing, taste and smell, open the list.
In a slightly lower ranking are a host of cellular and tissue functions. Just below these two groups are ranked genes responsible for the development of organs and tissues, and below them are genes belonging to hearing. With regard to this last group, the researchers suggest that an improvement in the ability to hear - and in particular the ability to distinguish between different sounds - can be used as a basis for the development of communication through spoken language. This is an interesting addition to the research that was published about six months ago in the journal "Nature", which reported on a positive selection in human evolution for a gene involved in the normal development of the ability to speak.
It is important to emphasize that even a very comprehensive study, which will locate many genes that present differences like those that were at the center of the study described above, will reveal only a small part of the "prescription" for creating a person, as the researchers also clearly point out. It is almost certain that the regulation of the expression patterns of these genes (and perhaps also genes that do not show a pattern of positive selection in human evolution), as well as complex interrelationships between the proteins that are the products of the genes, play central roles in the design of a human being.
Dr. Mokdi is a researcher and lecturer at the Nature Conservation Research Institute, Faculty of Life Sciences, Tel Aviv University. The article was first published in "Haaretz" on 22/1/04
