8:30AM - Breakfast
8:50AM - Welcome/Introduction [Organizers]
9:00AM - *Keynote Speaker : Gregory Barsh
:: Editor-in-chief of PLOS Genetics, Professor Emeritus of Genetics at Stanford University School of Medicine, Investigator at the HudsonAlpha Institute for Biotechnology ::
- Title: "Genetics of color variation in a post-genome world"
10:10AM - 1) Tami Lieberman - Alm Lab
- Title: Adaptation and Diversification of Commensal Bacteria Within Humans
- Summary: To share the first evidence that bacteria within the healthy gut microbiome are continuing to adapt under strong selective forces (with selective coefficients >1%), despite residence in mammalian guts for millions of years. Strong signals of adaptive evolution include parallel evolution at the gene level within people, elevated dNdS in these genes, and the observation of selective sweeps. Tracking this evolution reveals genes and pathways important to colonization, and may inform therapies for the manipulation of our microbiome. The particular evidence comes from tracking B. fragilis evolution in healthy people. Also, sharing a story about how we can use within-person evolution, even in the absence of strong selective pressures, to understand within-person migration and the in-vivo niches of our microbiota. We find that each individual's skin is colonized by multiple Propionibacterium acnes strains, some of which diversified and clonally expanded on their human host. Strikingly, P. acnes isolates taken from the same pore share mutations not found elsewhere on the face, suggesting that pores are distinct ecological units with limited migration
10:35AM - Coffee Break (30min)
11:05AM - 2) Mashaal Sohail and Brian Arnold (Joint talk) - Sunyaev Lab, and Hanage/Lipsitch Labs
- Title: Evolution of sex in bacteria
- Summary: Bacteria recombine by incorporating into their genomes DNA directly from the environment or from other cells. This recombination may simply swap one allele for another at a particular locus, breaking down linkage between mutations similar to crossover recombination in eukaryotes, but it may also involve the gain/loss of entire genes or operons. While the acquisition of novel genes may be advantageous, theoretical work suggests an evolutionary advantage for recombination due to its ability to facilitate natural selection against deleterious mutations via breaking down linkage disequilibrium (LD). This advantage only exists if negative LD is present between deleterious mutations in the population, meaning that deleterious mutations are less likely to be seen together on the same chromosome than expected by chance. We detect LD between non-synonymous mutations in bacterial genomes that is significantly negative when compared to LD between synonymous mutations. Moreover, when we further break down non-synonymous mutations, nonsense mutations show significant negative LD when compared to missense mutations. Further, the signal for negative LD is significant in a highly recombining species (Neisseria gonorrhea) but not in a lowly recombining species (Staphylococcus aureus), in line with classical theoretical arguments for the evolution of recombination. An intriguing question remains as to the source of the negative LD in bacterial genomes. Random forces such as genetic drift and population structure can lead to a net negative LD and thus the evolutionary maintenance of sex. On the other hand, deterministic forces such as epistatic interactions between deleterious mutations can also lead to net negative LD. We are doing simulation work to disentangle the evolutionary forces that generate negative LD and thus the evolution of sex in bacteria.
11:30AM - 3) Alexander Godfrey - Page Lab
- Title: Y-chromosome genes facilitated the evolution of female gene expression in humans
- Summary: The XY sex chromosomes of humans and other mammals evolved from an ordinary pair of autosomes present nearly 200 million years ago. Recombination between members of the autosomal pair was suppressed, transforming former alleles into pairs of independently segregating X- and Y-linked homologs. Although nearly all of these Y-linked homologs were degraded, a small number of widely expressed regulatory genes persist in differentiated X-Y pairs. Using large RNA-sequencing datasets from human tissues and from an avian outgroup species (chicken), we find that millions of years of sex-linked evolution allowed these genes to acquire novel, sex-specialized expression patterns. Y homologs that are expressed throughout the body are most highly expressed in the prostate gland, a fertility-promoting organ found only in male mammals. In parallel, X-chromosome genes that retained functional Y counterparts, but not other X-linked genes, became biased in their expression for the ovary and other tissues of the mammalian female reproductive tract. We propose that the survival of Y-chromosome genes lessened the constraints on their X homologs to function optimally in males, thereby facilitating the evolution of female adaptations.
11:55AM - 4) Anthony Geneva - Losos Lab
- Title: Population transcriptomics of ecologically differentiated anoles
- Summary: Advances in speciation genetics have led to a growing appreciation for the importance of adaptive evolution in driving the process of speciation. Much of this work and virtually all discovery of “speciation genes” have come from model organisms for which the ecological forces potentially driving adaptive evolution are unknown. The ecology of Anolis lizards is, in contrast, well characterized and relationships between traits and environmental factors strongly support the adaptive nature of many anole traits. Using a pair of ecologically differentiated and partially reproductively isolated Anolis species we are investigating genomic patterns associated with adaptive divergence and the evolution of reproductive isolation. Here, we report preliminary findings from population genomic, differential expression, and genomic cline analyses of these species to investigate the genomic consequences of ecological divergence.
12:20PM - Lunch (70min)
1:30PM - 5) Abigail Wark - Tabin Lab
- Title: Evolution and genetics of human hand proportions
- Summary: The unique shape of human hands enables us to grasp and manipulate objects in ways that set us apart from other primates. We want to understand how our specialized human hand shape is built genetically. Using a comparative approach, we have identified evolutionary changes in metacarpal length ratios that are likely to influence how humans grasp objects. We then used variation in these ratios in modern humans to perform an association study to identify genomic regions influencing handshape. By overlapping our association hits with bone growth regulatory maps and other in silico tools, we have identified both rare alleles of large effect and common variants with minor additive effects on metacarpal ratios. We are currently investigating several putative enhancers for potential regulatory roles in human hand shape development and evolution.
1:55PM - 6) Jenny Chen - Regev Lab
- Title: A Model for Expression Evolution Across the Mammalian Lineage
- Summary: The evolution of gene expression and its relationship to species phenotype is of considerable interest to the scientific community. However, no standard model for the evolution of expression currently exists to test the nature of selective forces acting on gene regulation. Using a comprehensive set of published and newly generated RNA-seq data spanning 7 tissues types across 17 species, we show that expression evolution is accurately modeled by an Ornstein-Uhlenbeck (OU) process, which enables us to identify genes under constrained, neutral, and accelerated expression evolution. Our work provides a theoretical framework for characterizing expression evolution that provides a crucial context for interpreting functional genomics data across species.
2:20PM - Coffee Break (25min)
2:45PM - 7) Molly Schumer - Reich Lab
- Title: Assortative mating drives persistent reproductive isolation in hybrids
- Summary: Assortative mating mediates reproductive isolation between species but its dynamics in natural populations are poorly understood. We find that strong assortative mating maintains reproductive isolation in a natural hybrid population of swordtail fish and has maintained the structure of this population over ~25 generations. Intriguingly, though in the wild these mate preferences result in nearly 100% of matings occurring between similar genotypes, this barrier breaks down in the lab. These results underscore the importance of assortative mating in shaping hybrid evolution and imply that short-term breakdown in assortative mating can have long-term evolutionary consequences.
3:10PM - 8) Victor Luria - Kirschner Lab
- Title: Variation and novelty in evolution: how new genes appear de novo and invent new protein structures
- Summary: While many new protein-coding genes arise through gene or genome duplication or by domain shuffling, in recent years it has become apparent that another class of new genes exists: novel genes that appear de novo, arising directly from intergenic genomic sequence. Combining mathematical modeling, structural bioinformatics and experiments, we set out to determine how often and how many novel genes can appear, what the general properties of this class of genes are and what kind of proteins they make. We have so far examined 8 animal and ciliate genomes and found that thousands of novel genes may appear de novo and may make proteins with biophysical properties that differ from those of ancient proteins. Since novel genes are almost invariably expressed in the nervous system and male germline, we are currently examining experimentally the function of several novel genes in the brain
3:35PM - 9) Inigo Olalde - Reich Lab
- Title: Western Europe during the third millennium BCE: A genetic characterization of the Bell Beaker Complex
- Summary: Bell Beaker pottery spread across western and central Europe beginning around 2750 BCE before disappearing between 2200–1800 BCE. The mechanism of its expansion is a topic of long-standing debate, with support for both cultural diffusion and human migration. To address this question, we generated genome-wide ancient DNA data from 170 Neolithic, Copper Age and Bronze Age Europeans, including 100 Beaker-associated individuals. The analysis of this remarkable amount of data yielded important insights into the population history of Europe during the 3rd millennium BCE.
4:00PM - Closing Remarks [Organizers]