Using novel advances in computational chemistry, we demonstrate that the set of 20 genetically encoded amino acids, used nearly universally to construct all coded terrestrial proteins, has been highly influenced by natural selection. We defined an adaptive set of amino acids as one whose members thoroughly cover relevant physico-chemical properties, or “chemistry space.” Using this metric, we compared the encoded amino acid alphabet to random sets of amino acids. These random sets were drawn from a computationally generated compound library containing 1913 alternative amino acids that lie within the molecular weight range of the encoded amino acids. Sets that cover chemistry space better than the genetically encoded alphabet are extremely rare and energetically costly. Further analysis of more adaptive sets reveals common features and anomalies and we explore their implications for synthetic biology. We present these computations as evidence that the set of 20 amino acids found within the standard genetic code is the result of considerable natural selection. The amino acids used for constructing coded proteins may represent a largely global optimum, such that any aqueous biochemistry would use a very similar set.

Multidisciplinary consensus indicates that half of the genetically amino acids are likely to have been available on the prebiotic earth, which implies certain adaptive expectations for the relationship between those amino acids and later additions to the genetic code. Chemistry space a concept that translates molecules to corresponding points in multidimensional space provides a framework for investigating these relationships. We therefore developed three tests to explore these implications using chemistry space to quantify otherwise qualitative questions.

Natural selection and relative isolation have shaped the genetics and physiology of unique human populations from Greenland to Tibet. Another such population is the Haenyeo, the all-female Korean divers renowned for their remarkable diving abilities in frigid waters. Apnea diving induces considerable physiological strain, particularly in females diving throughout pregnancy. In this study, we explore the hypothesis that breath-hold diving has shaped physiological and genetic traits in the Haenyeo. We identified pronounced bradycardia during diving, a likely training effect. We paired natural selection and genetic association analyses to investigate adaptive genetic variation that may mitigate the effects of diving on pregnancy through an associated reduction of diastolic blood pressure. Finally, we identified positively selected variation in a gene previously associated with cold water tolerance, which may contribute to reduced hypothermia susceptibility. These findings highlight the importance of traditional diving populations for understanding genetic and physiological adaptation.

We propose a metric which can be used to compute the amount of heritable variation enabled by a given dynamical system. A distribution of selection pressures is used such that each pressure selects a particular fixed point via competitive exclusion in order to determine the corresponding distribution of potential fixed points in the population dynamics. This metric accurately detects the number of species present in artificially prepared test systems, and furthermore can correctly determine the number of heritable sets in clustered transition matrix models in which there are no clearly defined genomes. Finally, we apply our metric to the GARD model and show that it accurately reproduces prior measurements of the model’s heritability.