S20-1

How transposable elements shape genome evolution through epigenetic mechanisms

Grace Yuh Chwen Lee¹

¹Department of Ecology and Evolutionary Biology, University of California, Irvine

Transposable elements (TEs) are widespread genome parasites whose presence is tightly intertwined with the evolution of their host genomes. Fifty years of transposon research primarily focused on how they break or change DNA sequences (“genetic effects”). Yet, growing evidence has suggested another important mechanism by which TEs impact genome function and evolution—through epigenetic silencing. Eukaryotic hosts typically silence TEs through the deposition of repressive epigenetic marks. While this silencing effect would reduce the replicative potential of TEs and should be beneficial to the hosts, our recent work found that epigenetic silencing of TEs also inadvertently results in harmful epigenetic effects both along the linear DNA and in 3D nuclear space. By using Drosophila as a model system, we identified genome-wide that repressive epigenetic marks at silenced euchromatic TEs spread to adjacent sequences, even into functional genes. This spreading effect changes the epigenetic states of neighboring genes and tampers gene expression. Silenced euchromatic TEs also spatially interact with distant pericentromeric heterochromatin, altering 3D genome organization. Importantly, population genomic analysis identified selection against both of these TE-mediated epigenetic effects, and, across Drosophila species, the strength of TE-mediated epigenetic effects is negatively associated with genomic TE abundance. These observed functional and evolutionary consequences indicate that TE-mediated epigenetic effect is not only crucial for the evolutionary dynamics of TEs, but also a significant contributor to host genome evolution.

S20-2

Timing and causes of evolution of human germline mutation spectrum

Ziyue Gao¹, Yulin Zhang³, Molly Przeworski^4,5, Priya Moorjani^2,3

¹Department of Genetics, University of Pennsylvania, Perelman School of Medicine
²Department of Molecular and Cell Biology, University of California, Berkeley
³Center for Computational Biology, University of California, Berkeley
⁴Department of Biological Sciences, Columbia University
⁵Department of Systems Biology, Columbia University

Recent studies have uncovered a multitude of differences in the mutation spectrum of polymorphic sites among human populations. However, such comparative studies are confounded by differences in demographic history, efficacy of selection, and strength of biased gene conversion between populations, so it is unclear to what degree the inter-population differences in polymorphism spectrum reflects evolution in the germline mutation spectrum. In addition, it is unknown how many independent changes in the mutational processes have happened during recent human evolution and when and where they took place. Moreover, causes of these changes are open to debate: while evolution of genetic modifiers and shifts in environmental exposures are leading hypotheses, changes in parental ages at reproduction alone are sufficient to shift the relative abundance of each mutation type, providing a simpler explanation for multiple simultaneous changes in the mutation spectrum. To estimate the magnitude and timing of changes in the human germline mutation spectrum and assess the contributions of the various potential causes, we compare the spectra of mutations that arose in different time windows of human evolution and relate them to the parental age effects on de novo mutations estimated from pedigree studies. After controlling for effects of selection and biased gene conversion, we find evidence of temporal changes of the mutation spectrum over time within human populations. We observe two independence changes after the split of African, European and East Asian populations, including the previously reported transient elevation in TCC>TTC mutation rate in Europeans, as well as a change in the ancestral population prior to the out-of-Africa migration. By relating these changes to data from pedigree studies, we find that shifts in reproduction ages alone cannot explain the various temporal variations observed for different mutation types. In summary, our results suggest that the human germline mutational processes have experienced multiple independent changes during the past 500,000 years. We also provide evidence that in addition to shifts in population-average reproduction age, changes at the molecular level, such as genetic modifiers and varying environments, have contributed substantially to the evolution of human germline mutation spectrum.

S20-3

Mutational processes in somatic cancer cell populations

Sayaka Miura ¹, Sudhir Kumar¹

¹Temple University

Mutational processes in somatic cancer cell populations constantly change, leaving their signatures in the accumulated genomic variation in tumors. The inference of mutational signatures from the observed genetic variation enables spatiotemporal tracking of mutational processes, which evolve due to cellular environmental changes, pre-existing mutations, and treatment regimes in tumors. Ultimately, mutational patterns illuminate the mechanistic understanding of their evolution in cancer progression. We show that the consideration of cancer cell phylogeny during mutational signature deconvolution results in higher-resolution detection of gain and loss of mutational processes within the phylogeny. This approach to analyzing somatic genomic variations in 61 lung cancer patients revealed a high turnover of mutational processes over time and closely related clonal lineages. Some mutational signatures (e.g., smoking-related) showed a higher propensity to be lost, whereas others (e.g., AID/APOBEC) were gained during lung tumor evolution. In addition to the usefulness of phylogeny-aware approaches to reveal the turnover of mutational processes, their usefulness, in general, will be briefly mentioned in other applications, such as reconstructing clone genotypes from bulk sequencing data, imputing missing data, and correcting base calls in single-cell sequences, inferring clone phylogenies, and reconstructing cancer migration paths.

S20-4

Intermolecular interactions drive protein adaptive and co-adaptive evolution at both species and population levels

Junhui Peng¹

¹The Rockefeller University, New York, NY 10065, USA

Proteins are the building blocks for almost all the functions in cells. Understanding the molecular evolution of proteins and the forces that shape protein evolution is an essential step in understanding the basis of function and evolution. Previous studies have shown that adaptation occurs frequently at the protein surface, such as in genes involved in host-pathogen interactions. However, it remains unclear whether adaptive sites are distributed randomly or at regions that are associated with particular structural or functional characteristics across the genome, since many of the proteins lack structural or functional annotations. Here, we seek to tackle this question by combining large-scale bioinformatic prediction, structural analysis, phylogenetic inference, and population genomic analysis of Drosophila protein-coding genes. Although adaptation is more relevant to function-related rather than structure-related properties, we observed that physical interactions may play a role in the co-adaptation of fast-adaptive proteins. Importantly, protein-protein and protein-DNA interaction sites are hotspots for protein adaptive evolution, regardless of the levels of intrinsic structural disorder or relative solvent accessibility. We found that strongly differentiated amino acids across geographic regions in protein coding genes are mostly adaptive, which may contribute to the long-term adaptive evolution. This strongly indicates that a number of adaptive sites are repeatedly mutated and selected in evolution, in the past, present, and maybe future. Our results suggest important roles of intermolecular interactions and co-adaptation in the adaptive evolution of proteins both at the species and population levels.

S20-5

Out of the Eastern Himalayan: Genomic signatures of global adaption in a widely distributed passerine, vinous-throated parrotbill (Sinosuthora webbiana)

Chun-Cheng Lee¹, Wen-Ya Ko², Wei Liang³, Shou-Hsien Li¹

¹Department of Life Science, National Taiwan Normal University, Taipei, Taiwan
²Department of Life Sciences and Institute of Genome Science, National Yang-Ming University, Taipei, Taiwan
³Department of Life Science, Hainan Normal University, Haiko, China

How organisms successfully colonized a new ecological environment is the central of the biological adaptation and diversification. However, little is known about the origin and genetic basis of traits underlying such processes. The vinous-throated parrotbill (Sinosuthora webbiana) is a small non-migratory passerine commonly found in East Asia. Unlike other Suthora species that restrict their ranges in the montane area of Eastern Himalayan, S. webbiana distributes in a broad latitudinal range (21.6- 45.3°N). By scanning their entire genomes, we detected signatures of genes under positive selection in both its southern (about 25°N) and northern (about 42°N) populations (global adaptation). We found that some of these genes are involved in metabolic pathways (e.g. FADS1, HMBS) and immune-related (e.g. UVRAG, LRIG2) functions. Phenotype enrichment analysis also supports phenotypic changes on behavioral/neurological and pituitary gland development (e.g. TRIM66, CDKN1B). The results shed the lights on how adaptation on physiological as well as behavioral traits might allow a montane avian lineage expanding into the novel ecological niche and occupying a broad range in East Asia. Keywords: Global adaptation, Ecological niche, Range expansion, Positive selection

S20-6

Evolution of an Adhesin Gene Family in Independently Derived Candida Yeast Pathogens

Bin He¹, Rachel Smoak¹, Lindsey Snyder¹, Michael Hart¹, Jan Fassler¹

¹Biology Department, the University of Iowa

Candida yeasts, as they were named, were found to belong to different phylogenetic groups separated by close, low pathogenic potential relatives. Despite their different evolutionary origin, a shared genomic trait in the Candida pathogens is a rich repertoire of cell wall proteins, including adhesins, a crucial virulence factor. In this study we characterized the evolution of a putative adhesin gene family in the newly emerging multidrug resistant Candida pathogen, C. auris, and investigated its evolution in the separately evolved C. albicans group. In C. auris, we found that the sequence features of several homologs in this family are highly similar to known fungal adhesins. Furthermore, the predicted structure of the N-terminal domain showed conformational similarity to unrelated bacterial adhesins, thus strongly implicating them as bona fide adhesion. Phylogenetically, we found this family is yeast-specific and has undergone massive expansions independently in the C. auris and the C. albicans groups. In contrast to the relatively conserved N-terminal domain, the C-terminal of the protein homologs showed rapid evolution in sequence composition and tandem repeat structures with potential implication for their different functions. In summary, we identified a novel candidate adhesin gene family in C. auris, and showed that the same protein family was repeatedly expanded in two separate Candida species groups; albeit the C-terminal region seemed to have either evolved separately or diverged significantly.