Selections in Molecular and Phenotypic Evolution

Selection plays an undoubtedly important role in evolution, yet our understanding remains limited. In this dissertation, I employed extensive genomic and phenotypic datasets to investigate the influence of natural selection on evolutionary processes at both the molecular and phenotypic levels. In Chapter 1, I challenged the neutral theory of molecular evolution by demonstrating that beneficial mutations are far more abundant than previously assumed. I proposed an adaptive tracking theory to reconcile this finding with the low substitution rate inferred from comparative genomics; under this theory, a natural population is always adapting to the rapidly changing environment, yet the beneficial mutations fueling the adaptation do not reach fixation due to antagonistic pleiotropy across environments. In Chapter 2, I investigated the genetic maintenance of human same-sex sexual behavior (SSB) and showed that modern contraception had disrupted a previously hypothesized evolutionary mechanism for maintaining SSB-associated alleles. In Chapter 3, I further distinguished between bisexual behavior (BSB) and exclusive SSB (eSSB) in their genetic basis, finding that BSB-associated alleles may confer reproductive advantages whereas eSSB-associated alleles are likely under negative selection. In Chapter 4, I examined the genetic architecture of the human sex ratio, identified the impact of large measurement error of sex ratio on its inferred heritability, and provided genomic evidence supporting Fisher’s principle. Finally, I addressed methodological aspects of evolutionary analysis: in Chapter 5, I uncovered biases in estimating fitness landscape ruggedness due to fitness measurement errors and proposed a correction; in Chapter 6, I introduced “effective fitness” as a more informative metric to quantify fluctuating selection with genetic drift. Collectively, the dissertation unifies diverse topics under the common theme of selection, challenging prevailing assumptions, and offering solutions to longstanding evolutionary puzzles concerning the evolution of DNA sequences and complex human traits.