Keywords
1. Evolutionary rate
2. Adaptation strength
3. Human proteins
4. Genetic polymorphism
5. McDonald-Kreitman method
Introduction
The study of human evolution through genomic data has long fascinated scientists, with efforts dedicated to understanding how genes adapt over time. A new paper published in ‘Nature Ecology & Evolution’ by Uricchio et al., reports the development of a sophisticated method to joint estimate the rate and strength of adaptive changes in protein-coding sequences in humans, highlighting the significance of weakly adaptive mutations and the adaptive response to viruses. Here, we dive deep into their findings, their impact on our understanding of human evolution, and the broader implications for evolutionary biology as a whole.
Background Selection and Its Impact on Genetic Variation
Background selection, the process by which deleterious mutations at linked sites are removed from a population, affects the genetic diversity around those sites. It represents a critical confounder in the identification of adaptation signals in genomic data. Previous studies have shown that neutral diversity is often constrained by such processes, with consequences for studying patterns of adaptation across species. The Cornell Laboratory of Ornithology, for example, has observed that background selection can have a profound impact on the genetic diversity of birds.
The McDonald-Kreitman Approach to Adaptation Inference
To isolate the signal of adaptation from the noise of background selection and neutral polymorphism, Uricchio and colleagues developed a method based on the classic McDonald-Kreitman test, which compares the ratio of non-synonymous to synonymous changes between species against the same ratio within species. This novel method provides an estimation of both the rate (α) and strength of adaptive changes in protein-coding DNA. The results were striking: the adaptation rate in human protein-coding sequences was estimated at α = 0.135, with 72% attributable to weakly beneficial variants.
Adaptation to Viruses: A Case of Stronger Selection Pressure
One of the most compelling findings of the study was the distinct pattern of adaptation seen in virus-interacting proteins. These proteins undergo adaptation at a rate nearly twice as frequent as the genome average (α = 0.224), and it appears that the adaptation involves more strongly beneficial mutations. The study suggests that humans face a higher selection pressure to adapt in the face of viral threats, which is consistent with other research suggesting that viruses are a significant driver of genetic adaptation.
Implications for Understanding Human Evolution
The methods and findings of Uricchio et al. provide a robust framework for inferring adaptation rates and strengths, which can be applied across diverse species. This research opens the door to a better understanding of the evolutionary forces shaping human proteins and the interaction between our genetic makeup and the environment. Notably, the study’s approach could be beneficial in understanding the genetic basis of complex diseases and could potentially influence future medical research.
Continuing Research on Selection and Evolutionary Pressures
Continued research in this area is vital to refine the models and techniques available for studying adaptation. The application of similar methods to other organisms could shed light on how different life forms respond to natural selection and the unique pressures they face. For example, Plant and Soil Sciences at the University of Delaware have employed related approaches to study crop adaptation to changing environmental conditions, underscoring the broad applications of this research.
Conclusion
By exploiting the selection at linked sites, Uricchio and his team have illuminated the intricate dance of adaptation occurring in human proteins. While the study focuses on the human genome, its implications ripple outwards, offering a new tool to the scientific community in their quest to decipher the complex mechanisms of evolution. As we unlock these genomic secrets, we edge closer to not only understanding our past but also to informing the health and wellbeing of future generations.
References
1. Uricchio, L. H., Petrov, D. A., & Enard, D. (2019). Exploiting selection at linked sites to infer the rate and strength of adaptation. Nature Ecology & Evolution, 3(6), 977–984. doi: 10.1038/s41559-019-0890-6.
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3. Kimura, M. (1968). Evolutionary rate at the molecular level. Nature, 217(5129), 624-626. doi: 10.1038/217624a0.
4. McDonald, J. H., & Kreitman, M. (1991). Adaptive protein evolution at the ADH locus in Drosophila. Nature, 351(6328), 652. doi: 10.1038/351652a0.
5. Pritchard, J. K., Pickrell, J. K., & Coop, G. (2010). The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Current Biology, 20(4), R208-R215. doi: 10.1016/j.cub.2009.11.055.
DOI: 10.1038/s41559-019-0890-6