Evolutionary Genomic Medicine: New approaches and challenges to understanding human health

The December, 2014, issue of Current Opinion in Genetics and Development (Vol 29) comprises a collection of review articles dedicated to the theme of “genetics of human origin.” The article by Rodríguez, Marigorta and Navarro[1] discusses the integration of genomic data and evolutionary medicine, a relatively new approach to the study of human health.

What is evolutionary medicine?

In the burgeoning field of evolutionary medicine[2] the principles and habits of mind of evolutionary biology are considered foundations for and are integrated with traditional research, education, training, and practices of medical and health professionals. One goal of evolutionary medicine is to use the concepts of evolutionary biology (i.e., adaptation, maladaptation, population genetics) to explore the etiology and presentation of human disease, vulnerability to disease, and anatomical and physiological correlates of genetic and environmental influences on human health.

What is medical genomics?

Rodríguez, et al. (2014:97) explain that “the field of medical genomics focuses on immediate questions about how diseases appear and how they advance within an organism.” To understand medical genomics, it is helpful to review what is meant by “the human genome.” Nearly all of your cells contain DNA[3]. DNA has a “double helix” structure – think of a ladder that has been twisted around its long-axis. The “rungs” of the DNA ladder are molecules called bases. There are four bases—A, T, C and G—and they pair up in a specific way: A pairs with T and C pairs with G. A typical human’s DNA is composed of approximately 3,000,000,000 base pairs packaged in 23 pairs of chromosomes (in each cell!). Among those 3 billion base pairs are very specific sequences of bases that are functional, meaning they play a role in the body’s physiological processes.

DNA double helix

DNA double helix structure

Most functional sequences within the DNA are referred to as genes. Many genes contain the instructions (via the order of the As, Ts, Cs and Gs) that tell the body what proteins to manufacture[4]. Human nuclear DNA[5] contains tens of thousands of functional DNA sequences, and the sum total of all the genes in human DNA is considered the human genome. The study of the human genome is called human genomics.

There are some clear associations between disease and mutated genes; the most familiar may be that of breast and ovarian cancer and the genes called BRCA1 and BRCA2. Mutations in the BRCA genes can prevent the body from producing proteins that suppress tumor growth. Rodríguez, et al. (2014:97) point out that in the 1960s and 1970s, “prior to the genomics era,” certain human leukocyte antigen (HLA) genes were associated with specific autoimmune conditions. Over the last decade, genome-wide association studies (GWAS) have sought to explore the complete human genome to identify the genetic loci[6] most frequently associated with a particular phenotype[7]. For example, GWAS have identified correlations between celiac disease, an autoimmune disorder, and mutations in genes called HLA-DQ2 and HLA-DQ8.  But how can genotype-phenotype associations such as these be evaluated or conducted in an evolutionary context to better understand and predict not only who is susceptible, but why certain people are susceptible to particular diseases? And what is the role of evolutionary genomic medicine (EGM) in improving diagnosis and treatment?

Integrating medical genomics and evolutionary medicine

In an age of companies like 23andMe[8], more people are aware of connections between genotype[9] and phenotype; however, the general public may not realize just how much is yet to be understood by researchers about the full extent of genotype-phenotype relationships, particularly with regard to disease susceptibility and/or adaptation. In their review article, Rodríguez, et al. explain why EGM is still a nascent discipline and requires novel approaches to more fully develop as a field of research.

As Rodríguez, et al. discuss, there have been successful cases in evolutionary genomic medicine – for example, the research and discoveries regarding sickle-cell anemia and lactose tolerance. So, why is it not common sense and commonplace strategy to interface genomics, evolution and medicine to study and better understand human diseases? Rodríguez, et al. (2014:98) discuss two “glaring gaps in our knowledge: the twin dissociations between health and fitness and between genotypes and phenotypes.” Fitness refers to reproductive fitness—the primary measure of success in the world of living organisms. An individual is “fit” if he or she has offspring and those offspring can also have offspring (more healthy, viable offspring equates to greater fitness). Hence, “survival of the fittest” refers to survival of those members of a population who successfully reproduce, thereby passing on their genes to future generations. The authors point out that fitness may or may not be affected by health and disease in some circumstances; so, adaptive (or maladaptive) explanations for diseased states can be difficult to identify or test. Additionally, what we now consider diseased states—those that are detrimental to health and/or fitness in some or all modern human populations—may have been adaptive phenotypes or evolutionary trade-offs in the past (i.e., the Pleistocene).

A deeper awareness of the relationships between genotype and phenotype and between health and fitness are needed to further advances in EGM, but there are steps that can be taken today to elucidate the etiology, estimated occurrence, diagnosis, and treatment of human disease in light of evolutionary biology.


[1] DOI: 10.1016/j.gde.2014.08.009

[2] See Nesse, R. http://www.randolphnesse.com/articles/darwinian-medicine for a list of useful articles and books about evolutionary medicine.

[3] Some cells, in particular red blood cells, which lack a nucleus, do not contain chromosomal DNA.

[4] Genes can also turn on and off, or regulate, other genes.

[5] Organelles called mitochondria also contain DNA, referred to as mtDNA.

[6] A genetic locus is a specific location in the DNA; loci are typically distinguished by letters and numbers that identify their position on a chromosome.

[7] Phenotype refers to the form or function of an organism’s body systems (e.g., eye color or whether or not a person exhibits the symptoms of a disease).

[8] 23andMe.com is a DNA analysis service now required by the U.S. Food and Drug Administration to report only on ancestry; prior to this regulation, the company also provided genetic information related health and disease susceptibility.

[9] A person’s genotype is determined by which versions, or alleles, of genes the person possesses.


About Paleophile

This is my personal blog and the views presented here are not those of any academic institution where I am enrolled, any agencies that choose to fund my research, or my places of employment. View all posts by Paleophile

One response to “Evolutionary Genomic Medicine: New approaches and challenges to understanding human health

  • Raju

    Good commentary…Please also take a look at “Opportunity for selection in human health.” Advances in Genetics 2014; 87:1-75.

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