Ontogeny and phylogeny: molecular signatures of selection, constraint, and temporal pleiotropy in the development of Drosophila

Livestock is heavily affected by trypanosomosis in Africa. Through strong selective pressure, several African indigenous breeds of cattle and small ruminants have acquired varying degrees of tolerance against this disease. In this study, we combined LFMM and PCAdapt for analyzing two datasets of goats from West-Central Africa and East Africa, respectively, both comprising breeds with different assumed levels of trypanotolerance. The objectives were (i) to identify molecular signatures of selection related to trypanotolerance; and (ii) to guide an optimal sampling for subsequent studies. From 33 identified signatures, 18 had been detected previously in the literature as being mainly associated with climatic adaptations. The most plausible signatures of trypanotolerance indicate the genes DIS3L2, COPS7B, PD5A, UBE2K, and UBR1. The last gene is of particular interest since previous literature has already identified E3-ubiquitin ligases as playing a decisive role in the immune response. For following-up on these findings, the West-Central African area appears particularly relevant because of (i) a clear parasitic load gradient related to a humidity gradient, and (ii) still restricted admixture levels between goat breeds. This study illustrates the importance of protecting local breeds, which have retained unique allelic combinations conferring their remarkable adaptations.

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Signatures of Selection in the Human Antibody Repertoire: Selective Sweeps, Competing Subclones, and Neutral Drift

10.1101/145052 ◽

2017 ◽

Cited By ~ 4

Author(s):

Felix Horns ◽

Christopher Vollmers ◽

Cornelia L. Dekker ◽

Stephen R. Quake

Keyword(s):

B Cell ◽

Antibody Repertoire ◽

Molecular Signatures ◽

Selective Sweeps ◽

Evolutionary Processes ◽

Neutral Drift ◽

Cell Lineages ◽

Somatic Evolution ◽

Antibody Repertoires ◽

Signatures Of Selection

AbstractAntibodies are created and refined by somatic evolution in B cell populations, which endows the human immune system with the ability to recognize and eliminate diverse pathogens. However, the evolutionary processes that sculpt antibody repertoires remain poorly understood. Here, using an unbiased repertoire-scale approach, we show that the molecular signatures of evolution are evident in human B cell lineages and reveal how antibodies evolve somatically. We measured the dynamics and genetic diversity of B cell responses of five adults longitudinally before and after influenza vaccination using high-throughput antibody repertoire sequencing. We identified vaccine-responsive B cell lineages that carry signatures of selective sweeps driven by positive selection, and discovered that they often display evidence for selective sweeps favoring multiple subclones. We also found persistent B cell lineages that exhibit stable population dynamics and carry signatures of neutral drift. By exploiting the linkage between B cell fitness and antibody binding affinity, we demonstrated the potential for using signatures of selection to identify antibodies with high binding affinity. This quantitative characterization reveals that antibody repertoires are shaped by an unexpectedly broad spectrum of evolutionary processes and shows how signatures of evolutionary history can be harnessed for antibody discovery and engineering.One Sentence SummaryMolecular signatures of somatic evolution reveal that diverse evolutionary processes ranging from strong positive selection to neutral drift sculpt human antibodies.

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