Phylomedicine is an emerging discipline at the intersection of

medicine Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pr ...

, genomics, and

evolution Evolution is change in the heritable characteristics of biological populations over successive generations. These characteristics are the expressions of genes, which are passed on from parent to offspring during reproduction. Variation ...

. It focuses on the use of evolutionary knowledge to predict functional consequences of mutations found in personal

genomes In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...

and populations.

History

Modern technologies have made

genome sequencing Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a ...

accessible, and biomedical scientists have profiled genomic variation in apparently healthy individuals and individuals diagnosed with a variety of diseases. This work has led to the discovery of thousands of disease-associated genes and genetic variants, elucidating a more robust picture of the amount and types of variations found within and between humans. Proteins are encoded in genomic DNA by exons, and these comprise only ~1% of the human genomic sequence (aka the

exome The exome is composed of all of the exons within the genome, the sequences which, when transcribed, remain within the mature RNA after introns are removed by RNA splicing. This includes untranslated regions of messenger RNA (mRNA), and coding re ...

). The exome of an individual carries about 6,000–10,000

amino-acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ami ...

-altering nSNVs, and many of these variants are already known to be associated with more than 1000 diseases. Although only a small fraction of these personal variants are likely to impact health, the sheer volume of known genomic and exomic variants is too large to apply traditional laboratory or experimental techniques to explore their functional consequences. Translating a personal genome into useful

phenotypic In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

information (e.g. relating to predisposition to disease, differential drug response, or other health concerns), is therefore a grand challenge in the field of

genomic medicine Medical genetics is the branch tics in that human genetics is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the caus ...

. Fortunately, results from the natural experiment of

molecular evolution Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics ...

are recorded in the genomes of humans and other living species. All genomic variation is subjected to the process of natural selection which generally reduces mutations with negative effects on phenotype over time. With the availability of a large number of genomes from the tree of life, evolutionary conservation of individual genomic positions and the sets of mutations permitted among species informs the functional and health consequences of these mutations. Consequently, phylomedicine has emerged as an important discipline at the intersection of

and genomic medicine with a focus on understanding the inherited component of human disease and health. Examples include studies of retinal disease, auditory diseases, and common diseases more generally. Phylomedicine expands the purview of contemporary evolutionary medicine to use evolutionary patterns beyond short-term history (e.g. populations within a species) to the long-term evolutionary history of multispecies genomics.

References

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