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Papula, A.

Publications and source records attributed to Papula, A..

2 recordsLinked to original sources

Extensive recombination, selection, and asexual blooms shapethe diversity of the dominant clade of Prochlorococcus

The tiny and enormously abundant marine cyanobacterium Prochlorococcus marinus contains many levels of population structure, with sequenced isolates spanning four orders of magnitude of diversity. It is divided into several major clades which exhibit the classic structure of distinct species, with little gene exchange across clade boundaries. The diversity within the dominant clade, High Light II (HLII), exceeds that of many bacterial species but exhibits little global population structure beyond some small tight genomic clusters. Few ecological distinctions within HLII have been found. What causes and sustains for millions of years the extensive diversity of this globally mixed population? In this work, hundreds of single cell genomes are analyzed and used to elucidate patterns of core and flexible gene flow, delineate subtle geographical correlations, and quantitatively test several scenarios for the evolutionary history of HLII. We find that recombination connects the entire HLII clade and that genes more than a few kb apart along the genome evolve largely independently. On shorter timescales, primarily-asexual blooms occur, but the clonal backbones of the resulting closely-related cell clusters are steadily eroded by recombination with the rest of HLII. Although a small number of genes have ocean-specific alleles, there is no evidence for genetically-stable ecotypes within the clade. We conjecture that spatiotemporally variable selection drives conditionally-beneficial variants of genomic segments to rise to high abundance while horizontally-transferring throughout the population.

evolutionary biology↗

The Evolutionary Dynamics and Fitness Landscape of Clonal Haematopoiesis

Somatic mutations acquired in healthy tissues as we age are major determinants of cancer risk. Whether variants confer a fitness advantage or rise to detectable frequencies by chance, however, remains largely unknown. Here, by combining blood sequencing data from [~]50,000 individuals, we reveal how mutation, genetic drift and fitness differences combine to shape the genetic diversity of healthy blood ( clonal haematopoiesis). By analysing the spectrum of variant allele frequencies we quantify fitness advantages for key pathogenic variants and genes and provide bounds on the number of haematopoietic stem cells. Positive selection, not drift, is the major force shaping clonal haematopoiesis. The remarkably wide variation in variant allele frequencies observed across individuals is driven by chance differences in the timing of mutation acquisition combined with differences in the cell-intrinsic fitness effect of variants. Contrary to the widely held view that clonal haematopoiesis is driven by ageing-related alterations in the stem cell niche, the data are consistent with the age dependence being driven simply by continuing risk of mutations and subsequent clonal expansions that lead to increased detectability at older ages.

genomics↗