Landscape of standing variation for tandem duplications in Drosophila yakuba and Drosophila simulans
Rebekah L. Rogers, Julie M. Cridland, Ling Shao, Tina T. Hu, Peter Andolfatto, Kevin R. Thornton
(Submitted on 28 Jan 2014)

We have used whole genome paired-end Illumina sequence data to identify tandem duplications in 20 isofemale lines of D. yakuba, and 20 isofemale lines of D. simulans and performed genome wide validation with PacBio long molecule sequencing. We identify 1,415 tandem duplications that are segregating in D. yakuba as well as 975 duplications in D. simulans, indicating greater variation in D. yakuba. Additionally, we observe high rates of secondary deletions at duplicated sites, with 8% of duplicated sites in D. simulans and 17% of sites in D. yakuba modified with deletions. These secondary deletions are consistent with the action of the large loop mismatch repair system acting to remove polymorphic tandem duplication, resulting in rapid dynamics of gain and loss in duplicated alleles and a richer substrate of genetic novelty than has been previously reported. Most duplications are present in only single strains, suggesting deleterious impacts are common. However, we do observe signals consistent with adaptive evolution. D. simulans shows an excess of whole gene duplications and an excess of high frequency variants on the X chromosome, consistent with adaptive evolution through duplications on the D. simulans X. We identify 79 chimeric genes in D. yakuba and 38 chimeric genes in D. simulans, as well as 143 cases of recruited non-coding sequence in D. yakuba and 96 in D. simulans, in agreement with rates of chimeric gene origination in D. melanogaster. Together, these results suggest that tandem duplications often result in complex variation beyond whole gene duplications that offers a rich substrate of standing variation that is likely to contribute both to detrimental phenotypes and disease, as well as to adaptive evolutionary change.

Demography and the age of rare variants
Iain Mathieson, Gil McVean
(Submitted on 16 Jan 2014)

Recently, large whole-genome sequencing projects have provided access to much of the rare variation in human populations. This variation is highly informative about population structure and recent demography. In this paper, we show how the age of rare variants can be estimated from patterns of haplotype sharing and how this information can detect and quantify historical relationships between populations. We investigate the distribution of the age of f2 variants in a worldwide sample sequenced by the 1,000 Genomes Project, revealing enormous variation across populations. The median age of f2 variants shared within continents is 50 to 160 generations for Europe and Asia, and 170 to 320 generations for Africa. Variants shared between continents are much older with median ages ranging from 320 to 670 generations between Europe and Asia, and 1,000 to 2,400 generations between African and Non-African populations. The distribution of the ages of variants shared across populations is informative about their demography, revealing recent bottlenecks, ancient splits, and more modern connections between populations. We see the signature of selection in the observation that functional variants are significantly younger than nonfunctional variants of the same frequency. This approach is relatively insensitive to mutation rate and complements other nonparametric methods for demographic inference.

Population genomics of Saccharomyces cerevisiae human isolates: passengers, colonizers, invaders.
Carlotta De Filippo, Monica Di Paola, Irene Stefanini, Lisa Rizzetto, Luisa Berná, Matteo Ramazzotti, Leonardo Dapporto, Damariz Rivero, Ivo G Gut, Marta Gut, Mónica Bayés, Jean-Luc Legras, Roberto Viola, Cristina Massi-Benedetti, Antonella De Luca, Luigina Romani, Paolo Lionetti, Duccio Cavalieri

The quest for the ecological niches of Saccharomyces cerevisiae ranged from wineries to oaks and more recently to the gut of Crabro Wasps. Here we propose the role of the human gut in shaping S. cerevisiae evolution, presenting the genetic structure of a previously unknown population of yeasts, associated with Crohn?s disease, providing evidence for clonal expansion within human?s gut. To understand the role of immune function in the human-yeast interaction we classified strains according to their immunomodulatory properties, discovering a set of genetically homogeneous isolates, capable of inducing anti-inflammatory signals via regulatory T cells proliferation, and on the contrary, a positive association between strain mosaicism and ability to elicit inflammatory, IL-17 driven, immune responses. The approach integrating genomics with immune phenotyping showed selection on genes involved in sporulation and cell wall remodeling as central for the evolution of S. cerevisiae Crohn?s strains from passengers to commensals to potential pathogens.