The value of broad taxonomic comparisons in evolutionary medicine: Disease is not a trait but a state of a trait!

Abstract

In this short paper, we argue that there is a fundamental connection between the medical sciences and evolutionary biology as both are sciences of biological variation. Medicine studies pathological variation among humans (and domestic animals in veterinary medicine) and evolutionary biology studies variation within and among species in general. A key principle of evolutionary biology is that genetic differences among species have arisen first from mutations originating within populations. This implies a mechanistic continuity between variation among individuals within a species and variation between species. This fact motivates research that seeks to leverage comparisons among species to unravel the genetic basis of human disease vulnerabilities. This view also implies that genetically caused diseases can be understood as extreme states of an underlying trait, that is, an axis of variation, rather than distinct traits, as often assumed in GWAS studies. We illustrate these points with a number of examples as diverse as anatomical birth defects, cranio‐facial variation, preeclampsia and vulnerability to metastatic cancer.

Skeletal muscle: molecular structure, myogenesis, biological functions, and diseases

“… 179 Recently, an interesting argument has been made that the genetic basis of human disease can be revealed through leverage comparisons among species. 180 Evolutionary homology between myomerger and FAST protein from Reoviridae family may provide ideas for genetic characteristic of some myopathies. 64 , 181 Based on these findings, cell–cell fusion deficits can become a new spectrum of congenital myopathy, providing new explanations and therapeutic targets for more diseases.…”

“…Additionally, muscle atrophy and abnormal athletic ability caused by spinal muscular atrophy are associated with the decreased expression of myomakers and myomergers, leading to myofiber fusion disorders 179 . Recently, an interesting argument has been made that the genetic basis of human disease can be revealed through leverage comparisons among species 180 . Evolutionary homology between myomerger and FAST protein from Reoviridae family may provide ideas for genetic characteristic of some myopathies 64,181 .…”

Evolutionarily new genes in humans with disease phenotypes reveal functional enrichment patterns shaped by adaptive innovation and sexual selection.

“…Such genetic variations underpin the ongoing evolution of human phenotypes, with beneficial mutations being fixed by positive selection, and detrimental ones being eliminated through purifying selection. In medical terminology, this spectrum is categorized as "case and control" or "disease and health," representing two ends of the phenotypic continuum (Pavličev and Wagner 2022). Approximately 8,000 clinical types of rare Mendelian disorders, affecting millions worldwide, are attributed to deleterious DNA mutations in single genes (monogenic) or a small number of genes (oligogenic) with significant effects (Antonarakis and Beckmann 2006;Fetro and Scherman 2020).…”