Disease consequences of human adaptation

Abstract

Adaptive evolution has provided us with a unique set of characteristics that define us as humans, including morphological, physiological and cellular changes. Yet, natural selection provides no assurances that adaptation is without human health consequences; advantageous mutations will increase in frequency so long as there is a net gain in fitness. As such, the current incidence of human disease can depend on previous adaptations. Here, I review genome-wide and gene-specific studies in which adaptive evolution has played a role in shaping human genetic disease. In addition to the disease consequences of adaptive phenotypes, such as bipedal locomotion and resistance to certain pathogens, I review evidence that adaptive mutations have influenced the frequency of linked disease alleles through genetic hitchhiking. Taken together, the links between human adaptation and disease highlight the importance of their combined influence on functional variation within the human genome and offer opportunities to discover and characterize such variation.

Biological relevance of computationally predicted pathogenicity of noncoding variants

“…These observations suggest that the accuracies reported during the development of predictive methods may not translate into high success rates when applied to fundamental empirical biological research questions. To test this proposition, we evaluate the performance of the aforementioned six predictive tools for three major biological tasks that represent common applications of pathogenicity predictions: distinguishing which of the four alleles at a causal site are pathogenic and which are protective (with implications for inferring how natural selection shapes variation at the locus 26 ), fine mapping the causal variant within a credible interval of physically proximate ncSNVs that have similar statistical evidence for association 27–29 , and ranking of candidate variants across the genome for prioritization of the likely disease-promoting gene(s). To avoid biases due to unknown cutoff values and class imbalance, we use relative ranks of pathogenic and non-pathogenic variants in balanced test sets as the performance metrics.…”

Positive and balancing selection onSLC18A1gene associated with psychiatric disorders and human-unique personality traits

“…Characteristics unique to humans might have evolved through natural selection, although these often resulted in disorders and diseases as by‐products of the adaptive evolution (Crespi et al ; Moalic et al ; Fay ; Ogawa and Vallender ). Psychiatric disorders (PDs), such as schizophrenia, autism, and depression, are generally characterized by cognitive dysfunction, social impairment, or affective disturbance and are very common in our modern society.…”

The influence of evolutionary history on human health and disease

“…A second explanation is mismatch between our biological legacy and our modern environments 184 . Mismatch between our biological adaptations to ancestral environments and modern lifestyles contributes to many common diseases, such as obesity, diabetes and heart disease, that are promoted by sedentary lifestyles and poor nutrition 185 , 186 . For example, past exposure to calorie-poor conditions may promote metabolically efficient ‘thrifty’ gene variants that may contribute to increased obesity in calorie-rich environments.…”