We traditionally envision adaptation of organisms to new environments as starting with appearance of a new favorable mutation and spreading to the population. While this view applies well to microbes, such as yeast or bacteria, it usually takes much longer for new mutations to arise and spread in large-bodied, less-abundant species, and when they do, they are more likely to be lost. Accordingly, natural selection acting on new mutations apparently was rare during the last 250,000 years of human evolution. An alternative view for adaptation that may apply well to humans is emerging; many mutations persist in populations for a long time as ?standing genetic variation? (SGV) even though they have weak or even adverse effects on chances to survive and reproduce (i.e., natural selection). When an environment changes or people migrate, variants in the SGV may become highly advantageous, allowing the population to adapt quickly to its new surroundings. There is growing evidence that SGV is crucial for adaptation of many species over short time scales, and is crucial for most complex human traits (including those for disease) and drug resistance in human pathogens (e.g., HIV). However, while examples of adaptation based on SGV in humans are growing, surprisingly little is known, either theoretically or empirically, about the ?evolutionary dynamics? of adaptation based on SGV. In the last five years, the Threespine Stickleback (TS, ?Gasterost?eus aculeatus) fish has emerged as the premier subject to study adaptation based on SGV. Sea-run stickleback contain abundant SGV and have repeatedly invaded fresh water. Much of their adaptation to fresh water occurs within a decade after they colonize it and depends on SGV. Indeed, SGV for the very same gene has apparently contributed to adaptation for skin pigmentation in both humans and TS on similar time scales (in generations). The overall goal of this project is to understand the evolutionary dynamics of adaptation based on SGV in TS.
The first aim to reach this goal is to sequence the genomes of ~1,000 marine TS from five Alaskan sea-run populations to identify genes with SGV and estimate the relative abundance of freshwater-adaptive SGV variants in the ancestral environment.
The second aim i s to sequence TS samples from three nearby Alaskan lakes annually for 10 years, including immediately after these lakes were colonized by sea-run TS. This will enable direct observation of how SGV changes in relative abundance during the earliest stages of adaptation, when most evolution from a sea-run to freshwater traits occurs.
The third aim i s to sequence a group of TS born simultaneously (i.e., a cohort) at biweekly to monthly intervals through the two-year life cycle in two new lake populations, allowing identification of which original SGV variants confer advantages for specific events during the life-cycle of adapting freshwater TS. This study will provide unique insights into the dynamics of adaptation based on SGV, which will be vital to better understand how humans and their pathogens adapt to new environments over short time scales.

Public Health Relevance

It is becoming increasingly apparent that adaptation from standing genetic variation is likely to underlie the majority of complex traits in humans (including those that cause complex disease). In addition, human pathogens appear to utilize standing genetic variation as a mechanism to evolve drug resistance. Our study of the genomics of Threespine Stickleback during the colonization of freshwater environments will provide unparalleled insights into the general process of adaptation from standing genetic variation.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Genetic Variation and Evolution Study Section (GVE)
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Janes, Daniel E
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State University New York Stony Brook
Schools of Arts and Sciences
Stony Brook
United States
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