Changing Seasons: Deciphering the Periodic Patterns of Gene Expression

FOUR SEASONS | A cartoon image showing the different seasons of the year: (L-R) Winter, Autumn, Spring, Summer. (Image source: www.smgs.nsw.edu.au)

By: Sean Lemuel L. Santos (Hybrizyme)

Life depends on the changing seasons. The yearly cycle of heat, cold, rain, and drought orchestrates the way organisms live. Seasons determine what plants will thrive and what plants will die within a given time. They tell when the migratory birds will leave and when they will go back. They dictate how long fishes will stay active and how long they will go to a deep, long slumber. It is therefore undeniable that life dances to the rhythm of nature. Now, scientists are trying to uncover the deeper roots of this relationship between organisms and the seasons. They are now looking into our genes—sections of our DNA that determine our traits—which might be the dials that the seasons are actually turning and tuning. Below are highlights of some researches that are revealing the unspoken connections between genes and the seasons.

Immunity Genes

In 2015, scientists from Cambridge University reported that around 4,000 human genes exhibit seasonal variation. Particularly, genes involved in immunity were more expressed in Europeans during the winter season. Scientists explained that this increased expression of ‘immunity genes’ acts as a defense mechanism against certain infections that are more prevalent during the cold months of Europe. They asserted that this seasonal expression of ‘immunity genes’ evolved during the time when humans first started to migrate out of Africa and into the colder European regions. There, they encountered and eventually co-evolved with infectious organisms adapted to cold climates. The researchers reported that among Gambians, however, ‘immunity genes’ were more active in rainy season, not winter. This is because, in Gambia, infectious diseases such as malaria tend to flare up during the rainy season so the immune system has to respond faster in this time of the year.

Cytokine Genes and Schizotypal Traits

Seasons can also influence genes involved in the emergence of schizophrenia, a mental disorder characterized by having delusions and hallucinations. In a 2017 study conducted by researchers from Russia, it was discovered that the interaction between a person’s birth season and cytokine genes can affect the development of schizotypal traits in the population (Cytokine genes code for cytokines which are proteins involved in inflammatory responses). Accordingly, among winter-born individuals, those with two bad copies of the IL4 gene have higher risks of developing schizotypal traits while those that have one or two good gene copies seem to have a protection against the development of schizotypal traits. Investigators suppose that higher levels of the anti-inflammatory cytokine IL-4, coded by the good copy of the IL4 gene, counteracts the onset of schizotypal traits by reducing abnormal neural activities caused by another cytokine called IL-1β.

Eotaxin Genes and Asthma

The birth season of a person might also be related to the onset of asthma, a disease caused by inflammation of the lungs leading to difficulty in breathing. In 2011, a study published in Genomics and Informatics examined the variations within the eotaxin-2 and eotaxin-3 genes of 78 asthma patients and 101 healthy individuals. These genes are found to be involved in the pathogenesis of asthma. The study conducted in Korea found out that the four seasons in Korea (summer, winter, fall, spring) influence the expression of eotaxin gene variations among children. The findings revealed that children who were born during summer or spring had significant eotaxin-2 and eotaxin-3 gene variations. This suggests the possibility of predicting the chances of having asthma by looking at the birth season of an individual.

Seasonal Genes and Reproduction

Can the seasons also affect the reproductive cycle? European researchers who published a 2014 study on circannual clock tried to answer this question. In their study, they investigated whether genes involved in measuring period of daylight (TSHβ and Dio2) and genes involved in the control of reproduction (Rfrp and Kiss2) show seasonal variations. In their experiment, they used European hamsters and removed their biological (pineal gland) and external (length of daylight) cues for seasonal changes. They then simulated seasonal changes to induce a year-round bodily rhythm on hamsters. Results showed that the TSHβ gene is seasonally expressed and that it is most highly expressed during summer. The study explained that TSHβ stimulates Dio2 expression in the hamster brain. This results to expression of Rfrp in the brain which in turn stimulates Kiss1. This Kiss1 gene, in turn, controls the activity of Gonadotropin-releasing hormone (GnRH)–a hormone involved in reproduction. Thus, it can be said that seasonal changes affect the expression of a cascade of genes involved in reproduction.

House-keeping Genes

It turns out that the changing seasons might actually be affecting molecular processes that happen inside our cells. In 2015, Anita Goldinger, a researcher from University of Queensland Diamantina Institute, and her colleagues studied whether changes in gene expression follow the changing seasons. In their study, they examined the genes of 606 healthy individuals and looked for genes that are exhibiting seasonal variations. They found out that there were 74 genes involved in DNA repair and binding and 94 genes involved in protein synthesis and immune processes that all show seasonal changes in expression. According to the study, the results indicate that the seasons act as environmental signals for gene expression which then affect molecular and bodily functions. The researchers thus noted that their study might explain why some diseases, such as psychiatric and cardiovascular diseases, occur more often during certain seasons of the year.

Stress-Response Genes

In 2014, a paper published in Cell Stress and Chaperones demonstrated that the expression HSP70 genes in Indian goats (Capra hircus) vary based on season (HSP70 genes code for heat-shock proteins that prevent misfolding of other cellular proteins).  The study focused on five HSP70 genes: HSPA8, HSPA1A, HSPA6, HSPA1L, and HSPA2. The results showed that during summer, HSPA8, HSPA1A and HSPA6 genes were more expressed compared to the other two genes. Meanwhile, during winter, HSPA8 and HSPA1A genes were more active than the other three genes. This suggests, according to the paper, that both heat-stress and cold-stress activated a certain set of HSP70 genes. It was also observed that HSP70 genes were more expressed during summer in cold-adapted goats and during winter in heat-adapted goats. The researchers conclude that the expression of HSP70 genes depends on the species and breed of goat which have their own adaptations to the changing climate and temperature.

        The changing seasons do really change us. The researches discussed above have revealed that genes obey the commands of the seasons. 

              Indeed, we cannot separate ourselves from nature. We are intertwined to its seasons. We are carried by its repeating music that have danced with us, residents of this living planet, for billions of years.

References:

Ahn, I., Bae, S.-E., Kim, J. H., Son, B. K., Son, H. S., & Cho, S.-I. (2011). Genetic Association between Eotaxin Genes and Asthma and Its Relationship to Birth Season in Korean Children. Genomics & Informatics, 12-18.

Alfimova, M. V., Korovaitseva, G. I., Lezheiko, T. V., & Golimbet, V. E. (2017). Interaction Effects of Season of Birth and Cytokine Genes on Schizotypal Traits in the General Population. Schizophrenia Research and Treatment, 1-8.

Banerjee, D., Upadhyay, R. C., Chaudhary, U. B., Kumar, R., Singh, S., Ashutosh, . . . De, S. (2014). Seasonal variation in expression pattern of genes under HSP70 family in heat and cold-adapted goats (Capra hircus). Cell Stress and Chaperones, 401-408.

Dopico, X. C., Evangelou, M., Ferreira, R. C., Guo, H., Pekalski, M. L., Smyth, D. J., . . . Todd, J. A. (2015). Widespread seasonal gene expression reveals annual differences in human immunity and physiology. Nature Communications. doi:10.1038/ncomms8000

Goldinger, A., Shakhbazov, K., Henders, A. K., McRae, A. F., Montgomery, G. W., & Powell, J. E. (2015). Seasonal Effects on Gene Expression. PLoS ONE. doi:10.1371/journal.pone.0126995

Miera, C. S., Monecke, S., Bartzen-Sprauer, J., Laran-Chich, M.-P., Pevet, P., Hazlerigg, D. G., & Simonneaux, V. (2014). A Circannual Clock Drives Expression of Genes Central for Seasonal Reproduction. Current Biology, 1500-1506.