The complex nature of genetics and its wide implications for all living organisms from viruses to humans provide raw materials for creative imaginations. In the present scenario, many consider it vital to comprehend all the genetic information necessary to support life on this universe. One of the common constraints on the understanding of genetics is the assumption that genes are the sole causes of all activities of living organisms and can explain all aspects of biological life on earth. For example, some believe the behavior and development of an organism can be predicted, if its genetic information is known-this belief is called “genetic determinism.” However, it is true that neither all aspects of inheritance are in all cases well explained, nor that the mere effect of genes on complex traits is well interpreted. The boundaries of the effects of genes on physical existence, development, survival, and the behavior of organisms are not always simple and straightforward. The capacity of humans for genetic manipulation-at least as it is commonly assumed or claimed-is limited in several ways and some of the basic causes of such barriers have yet to be explained. The focus of this article is to point out the limitations on attempts to appoint genes as the driving force of life.
The Central Dogma
Genes are small fragments of genomic DNA, encoding mRNAs which are later translated into proteins that participate in different biological metabolisms, hence conferring different traits on an organism. The biological functions and transmission patterns of genes over generations were being investigated well before the discovery of DNA as hereditary material and date back to the recognition of Mendel’s laws in the early twentieth century. Genetic information is coded in the form of a short string of DNA called a gene, which is employed in the expression of a trait(s) or mechanism(s) through synthesizing a chain of amino acids called proteins. These proteins either can be stored in different body parts or serve as enzymes in various biochemical reactions such as fighting infections. This flow of genetic information from gene–mRNA–protein synthesis is called the “Central Dogma” in biological sciences. In this biological doctrine, a very solid and predictable mechanism is assumed. Prior to the release of the human genome sequence information, the number of genes in the human genome was estimated as ~100,000. However, this estimate was far more than the actual number of genes (~35,000), which led us to question the validity of the “Central Dogma” as an explanation of the complexity of human beings. Out of these ~35,000, only 300 genes are unique to the human species. 1 This is another blow to the authenticity of the original central dogma theory. Are those 300 genes the foundation of all humankind and do they distinguish us from the rest of the mammals? Reducing humankind to its biology and explaining it based on genes has been questioned extensively and could be the subject of another discussion. But even considering such a view valid for purely practical purposes, the big gap between humans and other mammals cannot be due to the existence of this small number of genes.
Recent scientific discoveries have revealed a key point about the structure of genes-that each gene has a set of sub-segments called exons. Each exon can make a new protein. Hence, the gene can be the template for more than one protein. In the presence of other genes and proteins, the code of a particular gene can yield different kinds of proteins under variable circumstances. The flow of information can be both ways, and hence there are no predetermined factors controlling the flow of information. That means, we might know the information on what genes are present, and we can even decode it to know what is in there, but we cannot be sure what result (proteins in this context) will come out at the end when it is in the context of real life.
From physical characteristics to their genetics
Working back from a particular trait and trying to infer the genes that are involved in expression of such trait is a different approach to reveal the role of genes but surely it is not an easy task. Traits that are expressed by a single gene or a small number of genes are known as Mendelian/qualitative traits and their pattern of inheritance is simple and detection of the gene(s) is straightforward. Some of the disease resistance in plants and blood groups in humans are classic examples of Mendelian traits. The main distinction between such traits and the quantitative ones is their discreteness. For example a human being can have only one of four blood types: A, B, AB or O, and each of these groups is solid and no other blood types exist in between. In this type of trait, the role of a particular gene(s) is usually predictable and the pattern of transmissions over generations both for the future and the past can be inferred.
However, only a small percentage of traits is qualitative and expresses Mendelian inheritance. Most traits, such as intelligence, skin color in humans, height of an organism, seed yield of a grain, and diseases that have genetic causes like cancer, are quantitative traits and complex in nature. The ultimate phenotype (what we can see or measure from a trait) emerges from the joint effect of many genes as well as interaction with the particular environment in which the individual develops. The number of genes that is involved in the expression of a particular trait can be hundreds or even more. An objective assessment of each trait and quantification (called the phenotype) is impractical in most cases and could lead to another discussion. But assuming that we can measure a trait feasibly, the inference of genetic bases could still be controversial. Considerable efforts have been devoted to unveiling the effect of genes in the expression of complex traits whose inheritance pattern deviates from Mendelian inheritance. A special genetic technique, known as genetic mapping, is used to identify multiple genes that underlie a complex trait and this has practical applications for crop improvement. In humans, efforts are directed toward the detection of genes which predispose to complex inherited diseases. In this type of situation, the effects of genes on a trait are additive and can only explain a certain amount of change in the trait that we are interested in. Detection of all genes involved in the expression of a quantitative trait is practically impossible. The environment is an important factor with a pivotal role in the expression of such traits. The term “environment” is not restricted to what is present within the cell or surrounding the cell or individual. It rather refers to larger scale effects in the process of biological life that cannot be explained by genetics and the term can be used interchangeably with non-genetic effects.
One of the most striking examples of the role of genes on the expression of the phenotype is the presence of differences between identical twins. Despite the fact that they have completely identical sets of genes, studies have shown that twins can indicate different degrees of psychiatric diseases such as bipolar disorder. 2 Similar phenomena may be observed in crop species. In crop breeding programs different varieties are usually tested in different environments. In most cases varieties rank differently based on their performance in different environments. 3
Genes that do not code any information for the trait of interest can also be a part of the process of expression of the trait. In other words, certain genes can be employed to stop or alter the function of a particular gene. Modifying the utility of a gene can also be done by a series of complicated reactions within each organism through mechanisms known as epigenetics. This type of alteration in gene function is also observed empirically during the process of transferring genes between different organisms through genetic engineering. 4 Most transferred genes are silenced (turned off) by different mechanisms in a new organism regardless of patterns of inheritance. This is particularly interesting because it clearly indicates that the existence of a particular gene in the body does not necessarily guarantee that it will be functional. Even if it is functional in one individual, it might be silent in others. Even if a gene is functioning in all the individuals carrying it, the degree of expression may be variable.
The end of genetic determinism
With the discovery of the code of genes, we now know more about the biology of living organisms than ever before, as new genetic tools have enabled us to better understand what kind of information is stored in each gene.
Most of the traits of living organisms are affected by the existence of many genes as well as non-genetic effects (denoted as environment in genetics). Although Mendelian traits can be predictable to some degree, yet we can not completely infer all the genes that are employed in the expression of a complex trait, nor the amount of contribution from each single gene and portion attributed by non-genetic factors. So we cannot determine the presence of genes by simply observing the phenotype or expression of a trait.
Considering each individual gene separately will allow us to understand its possible functions more clearly and accurately. Nevertheless, the knowledge of possible functions and structure is not enough to predetermine if the information coded in the gene will be used by the organism, and, even if it will be used, how much of that information will be processed is uncertain. Whether the information that is processed will be observed or not is another ambiguity.
Assuming that we can and will know all components of life by having the knowledge of genes is known as genetic determinism. In some cases, genes are described as independent entities that drive living organisms and manage life because of the assumption that their presence will be enough to predetermine all the biology and the behavior of an organism.
Simply, in order for a gene to be an independent agent by itself, it needs to have the knowledge of all other genes as well as all the non-genetic factors for expression of a simple trait. In reality, genes contain a very limited amount of knowledge which makes them no more than tools or parts of living organisms that are employed in the existence of life on earth. Biological life itself is incredibly complex and its sustainability requires a more comprehensive knowledge that is beyond our current understanding based on the genetic code.
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C. L.G. Comstock, C. Davis, B. Ewing, S. Oommen, C. Lau, H. Yu, J. Li, B. A. Roe, P. Green, D. S. Gerhard, G. Temple, D. Haussler, and M. R. Brent. 2007. “Targeted
discovery of novel human exons by comparative genomics.”
Genome Research. Cold Spring Harbor Laboratory Press; ISSN 1088-9051/07; www.genome.org
2. Cardno, A. G., Rijsdijk, F. V., Sham, P. C., Murray, R. M. & McGuffin, P. “A Twin Study of Genetic Relationships Between Psychotic Symptoms.” 2002. Am. J. Psychiatry 159, 539-545
3. Epinat-Le Signor, C., S. Dousse, J. Lorgeou, J.B. Denis, R. Bonhomme, P. Carolo, and A. Charcosset. 2001. “Interpretation
of genotype x environment interactions for early maize hybrids over 12 years.” Crop Sci. 41:663–669
4. Kooter, J.M., Matzke, M.A., and Meyer, P. 1999. “Listening to the silent genes: Transgene silencing, gene regulation and pathogen control.” Trends Plant Sci. 4: 340–347