When it comes to determining an organism's traits, are genes really everything? Learn more about how our genes are controlled and what this means for the investigation of human diseases.

These days, it would appear that genes determine "everything" when it comes to an organism's traits. The impact of the environment on biology, however, cannot be disputed. For instance, almost everyone is aware of how crop harvests can be ruined by a dry season. But looking a bit closer turns up even more fascinating instances of how the environment affects living things. For instance, studies have revealed that the temperature at which some species of reptiles' eggs are incubated during development affects the sex of the reptiles. This type of observation seems paradoxical because it goes against the conventional wisdom that sex is determined by genes, not environment.

Thus, it would seem that there are some circumstances when the environment influences an organism's usage or deployment of its genes as well as its growth and health. Does this imply that genes may not be everything after all? The fact that genetically identical species frequently exhibit significant phenotypic diversity supports the idea that gene-environment interaction plays a significant role in controlling phenotypic variation, including variance associated with a variety of illnesses. In reality, in recent years more attention has been paid to the influence of environmental factors on the etiology (or cause) of disease. As a result, it has been determined that genes and environment can both have an impact on disease—not just individually, but also in direct contact with one another. This relatively new approach poses significant obstacles and unanticipated results.

Environmental Influences on Phenotype

Environmental influences on the development of animal features have long been recognized by scientists. Environmental elements can change which genes in an animal are expressed, which in turn impacts the animal's phenotype. These environmental factors include nutrition, temperature, oxygen levels, humidity, light cycles, and the presence of mutagens. This is why researchers who investigate the genetics of model organisms typically aim to reduce environmental influence by keeping the environment of the species under investigation consistent. The ability of modest environmental variations on gene expression is demonstrated by the fact that even genetically identical creatures subjected to carefully control experimental circumstances can have diverse phenotypes.

Detecting Changes in the Environment

Naturally, most creatures are subject to varying environmental conditions, and in these circumstances, it is frequently challenging to imagine how the organisms' genes may "sense" changes in the environment. Think about the crocodile's situation. How does the DNA in the egg "learn" about temperature changes? Scientists are aware that the temperature at which a crocodile egg is incubated affects the sex of the new born crocodile that emerges. Furthermore, how does the egg "know" to change the expression of genes to shift the sex of the growing crocodile upon perceiving such changes?

Studies have revealed that the gonadal tissue of some species is sensitive to temperature during a particular stage of development known as the thermosensitive period (TSP). This tissue transforms into ovaries when exposed to one range of temperatures, and transforms into testes when exposed to another range. Such is the situation with the turtle Emys obicularis: all of these turtles are born male while incubation temperatures are 25°C, but all are born female when temps are 30°C. The embryonic gonads all appear the same before the TSP, but something happens during the TSP that instructs the tissues to become either ovaries or testes.

It is this "something"—a change in gene expression—that causes the tissue to differentiate into its new identity. In particular, it has been demonstrated that the Sox9 gene's expression alters in response to temperature, being highly expressed at lower temperatures and suppressed at higher temperatures. The expression of this gene changes as temperature (and consequently Sox9 expression) changes, resulting in a distinct phenotype of maleness or femaleness. This is because the transcription factor produced by Sox9 impacts a gene that plays a significant role in sex determination.

Genes That Change the Environment

An organism's genotype may occasionally change the cellular environment. Consider the difference in enzyme activity. Researchers have discovered polymorphisms in a variety of human enzymes, including those that modify how each person reacts to various substances. Lower et al.'s (1979) research was one of the first to link enzyme activity to various phenotypes. This investigation focused exclusively on N-acetyltransferase activity. Specifically, the slow-acetylator phenotype was found to be associated with reduced N-acetyltransferase activity and a higher prevalence of bladder cancer.

What was the relationship?

What was the relationship between these two findings, though? It turns out that the liver, an organ that is crucial in the breakdown of potentially harmful substances, frequently exhibits high levels of N-acetyltransferase activity. These substances include acrylamine, a recognized carcinogen that smokers and some factory employees are exposed to more frequently. Because N-acetyltransferase is involved in the detoxification of acrylamine, research participants who detoxified acrylamine more slowly (i.e., the slow acetylators) were exposed to the carcinogen for longer and perhaps at larger quantities than participants who had the fast-acetylator phenotype. As a result, delayed acetylation changed the environment (by increasing acrylamine exposure), which in turn raised the prevalence of a specific disease phenotype (bladder cancer).

More recently, researchers have looked at the potential effects of human polymorphisms on the efficiency of chemoprevention, or the use of drugs to prevent cancer. For instance, evidence indicate that daily low-dose aspirin use, which has long been associated with improved heart health, may also reduce certain patients' risk of colon cancer. Two studies in particular found a link between aspirin use and cancer prevention, but only in one subset of users – those with a particular genotype of the aspirin metabolism gene UGT1A6. Only the group of patients with slow aspirin metabolizers showed protection from cancer (Figure 2). Unknown is the precise mechanism by which aspirin exerts its protective effects.

Numerous genes, numerous environmental factors, and numerous phenotypes

Researchers are unable to anticipate the amount of conceivable combinations of various genotypic variations, environmental factors, and potential phenotypes. But given the intricate relationships between numerous genetic loci and various environmental signals, researchers must keep coming up with new approaches to study these circumstances. One such approach is to simultaneously analyse thousands of genes using methods like microarray technology in various environmental settings. The combination of genes and environment must be taken into account in our research while trying to understand biology and human disease, even if we may never be able to anticipate an exact phenotype.




Gene–environment interactions and their impact on human health

Samuel J. VirolainenAndrew VonHandorfKenyatta C. M. F. VielMatthew T. Weirauch & Leah C. Kottyan (2023)



Environment Controls Gene Expression: Sex Determination and the Onset of Genetic Disorders

Amy Ralston, A. & Shaw, K. (2008)