Biology subjects

Jing Li

Publications and source records attributed to Jing Li.

3 recordsLinked to original sources

bioRxiv2016

Contrasting genome dynamics between domesticated and wild yeasts

Structural rearrangements have long been recognized as an important source of genetic variation with implications in phenotypic diversity and disease, yet their evolutionary dynamics are difficult to characterize with short-read sequencing. Here, we report long-read sequencing for 12 strains representing major subpopulations of the partially domesticated yeast Saccharomyces cerevisiae and its wild relative Saccharomyces paradoxus. Complete genome assemblies and annotations generate population-level reference genomes and allow for the first explicit definition of chromosome partitioning into cores, subtelomeres and chromosome-ends. High-resolution view of structural dynamics uncovers that, in chromosomal cores, S. paradoxus exhibits higher accumulation rate of balanced structural rearrangements (inversions, translocations and transpositions) whereas S. cerevisiae accumulates unbalanced rearrangements (large insertions, deletions and duplications) more rapidly. In subtelomeres, recurrent interchromosomal reshuffling was found in both species, with higher rate in S. cerevisiae. Such striking contrasts between wild and domesticated yeasts reveal the influence of human activities on structural genome evolution.

Genomics↗

bioRxiv2016

Background-dependent effects of selection on subclonal heterogeneity

In BriefVazquez-Garcia et al. examine the role of clonal heterogeneity in the acquisition of antimicrobial resistance. They report that pre-existing and de novo genetic variation jointly contribute to clonal evolution. By building a library of adaptive mutations in multiple genetic backgrounds, they resolve the fitness effects of mutations in a clonal lineage.\n\nHighlightsO_LIClonal heterogeneity influences the acquisition of antimicrobial resistance\nC_LIO_LIJoint role of pre-existing and de novo genetic variation in clonal evolution\nC_LIO_LIClonal dynamics are shaped by background-dependent fitness effects of mutations\nC_LIO_LILoss of clonal heterogeneity is balanced by genomic instability and diversification\nC_LI\n\nSummaryThe joint contribution of pre-existing and de novo genetic variation to clonal adaptation is poorly understood, but essential to design successful antimicrobial or cancer therapies. To address this, we evolve genetically diverse populations of budding yeast, S. cerevisiae, consisting of diploid cells with unique haplotype combinations. We study the asexual evolution of these populations under selective inhibition with chemotherapeutic drugs by time-resolved whole-genome sequencing and phenotyping. All populations undergo clonal expansions driven by de novo mutations, but remain genetically and phenotypically diverse. The clones exhibit widespread genomic instability, rendering recessive de novo mutations homozygous and refining pre-existing variation. Finally, we decompose the fitness contributions of pre-existing and de novo mutations by creating a large recombinant library of adaptive mutations in an ensemble of genetic backgrounds. Both pre-existing and de novo mutations substantially contribute to fitness, and the relative fitness of pre-existing variants sets a selective threshold for new adaptive mutations.

Genetics↗

bioRxiv2015

A Chronological Atlas of Natural Selection in the Human Genome during the Past Half-million Years

The spatiotemporal distribution of recent human adaptation is a long standing question. We developed a new coalescent-based method that collectively assigned human genome regions to modes of neutrality or to positive, negative, or balancing selection. Most importantly, the selection times were estimated for all positive selection signals, which ranged over the last half million years, penetrating the emergence of anatomically modern human (AMH). These selection time estimates were further supported by analyses of the genome sequences from three ancient AMHs and the Neanderthals. A series of brain function-related genes were found to carry signals of ancient selective sweeps, which may have defined the evolution of cognitive abilities either before Neanderthal divergence or during the emergence of AMH. Particularly, signals of brain evolution in AMH are strongly related to Alzheimers disease pathways. In conclusion, this study reports a chronological atlas of natural selection in Human.

Evolutionary Biology↗