Hybrid origins and the earliest stages of diploidization in the highly successful recent polyploid Capsella bursa-pastoris
Gavin Douglas, Gesseca Gos, Kim Steige, Adriana Salcedo, Karl Holm, J. Arvid ?gren, Khaled Hazzouri, Wei Wang, Adrian E. Platts, Emily B. Josephs, Robert J. Williamson, Barbara Neuffer, Martin Lascoux, Tanja Slotte, Stephen Wright

Whole genome duplication events have occurred repeatedly during flowering plant evolution, and there is growing evidence for predictable patterns of gene retention and loss following polyploidization. Despite these important insights, the rate and processes governing the earliest stages of diploidization remain uncertain, and the relative importance of genetic drift vs. natural selection in the process of gene degeneration and loss is unclear. Here we conduct whole genome resequencing in Capsella bursa-pastoris, a recently formed tetraploid with one of the most widespread species distributions of any angiosperm. Whole genome data provide strong support for recent hybrid origins of the tetraploid species within the last 100-300,000 years from two diploid progenitors in the Capsella genus. Major-effect inactivating mutations are frequent, but many were inherited from the parental species and show no evidence of being fixed by positive selection. Despite a lack of large-scale gene loss, we observe a shift in the efficacy of natural selection genome-wide. Our results suggest that the earliest stages of diploidization are associated with quantitative genome-wide shifts in the strength and efficacy of selection rather than rapid gene loss, and that nonfunctionalization can receive a ‘head start’ through deleterious variants found in parental diploid populations.

Probabilities of Fitness Consequences for Point Mutations Across the Human Genome
Brad Gulko, Ilan Gronau, Melissa J Hubisz, Adam Siepel

The identification of noncoding functional elements based on high-throughput genomic data remains an important open problem. Here we describe a novel computational approach for estimating the probability that a point mutation at each nucleotide position in a genome will influence organismal fitness. These fitness consequence (fitCons) scores can be interpreted as an evolution-based measure of potential genomic function. We first partition the genome into clusters of positions having distinct functional genomic “fingerprints,” based on cell-type-specific DNase-seq, RNA-seq, and histone modification data. Then we estimate the probability of fitness consequences for each cluster from associated patterns of genetic polymorphism and divergence using a recently developed probabilistic method called INSIGHT. We have generated fitCons scores for three human cell types based on publicly available genomic data and made them available as UCSC Genome Browser tracks. Like conventional evolutionary conservation scores, fitCons scores are clearly elevated in known coding and noncoding functional elements, but they show considerably better sensitivity than conservation scores for many noncoding elements. In addition, they perform exceptionally well in distinguishing ChIP-seq-supported transcription factor binding sites, expression quantitative trait loci, and predicted enhancers from putatively nonfunctional sequences. The fitCons scores indicate that 4.2-7.5% of nucleotide positions in the human genome have influenced fitness since the human-chimpanzee divergence. In contrast to several recent studies, they suggest that recent evolutionary turnover has had a relatively modest impact on the functional content of the genome. Our approach provides a unique new measure of genomic function that complements measures based on evolutionary conservation or functional genomics alone and is particularly well suited for characterizing turnover and evolutionary novelty.