Young human disease genes evolve slowly

Genes underlying human heritable diseases are not only important for medicine but are also of great interest for evolutionary biologists. This is because we know that such genes can be mutated to produce deleterious phenotypes and we can use them to study how function is acquired in evolution. In a paper just published in Genome Biology and Evolution and spearheaded by James Cai we show that disease genes evolve under strong functional constraint independently of their genomic age. This is quite different from other genes which show a marked trend of weaker constraint for genes that entered human genome more recently in evolutionary terms. Disease genes also tend to be expressed only in some tissues and appear to lack close duplicate copies. We argue that disease genes possess these features because they need to be sufficiently important such that mutations in them can be of noticeable functional significance. However, their expression and impact need to be limited to particular tissues because mutations in important genes expressed ubiquitously would generate embryonic lethals instead of disease. Finally, we believe that young human genes that evolve under strong constraint in humans might in general be enriched for genes that encode important primate or even human-specific functions. The study of such genes might be profitable and we intend to pursue this line of research in the future.