Relaxed Selection Limits Lifespan by Increasing Mutation Load

Cui, Rongfeng; Medeiros, Tania; Willemsen, David; Iasi, Leonardo Nicola Martin; Collier, Glen E.; Graef, Martin; Reichard, Martin; Valenzano, Dario Riccardo

doi:10.1016/j.cell.2019.06.004

Cited by 111 publications

(141 citation statements)

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“…The pseudogenomes for Nothobranchius orthonotus and Nothobranchius rachovii were generated from sequencing data and the same method used in Cui et al 4 . Briefly, the sequencing data were mapped to the NFZ v2.0 reference genome by BWA-mem v0.7.12 in PE mode 56, 57 .…”

Section: Methodsmentioning

confidence: 99%

“…Overall, relaxed selection in the dry GNP population affected accumulation of deleterious mutations in age-related and in the WNT pathway. Analysing the pathways affected by genes within the upper 2.5 th DoS values – corresponding to genes undergoing adaptive evolution – we found a significant enrichment for mitochondrial pathways – potentially compensatory 42 – in population NF303 (Figure5b, Table S9 ). Overall, our results show that differences in effective population size among wild turquoise killifish are associated with an extensive relaxation of purifying selection, significantly affecting genes involved in age-related diseases, and which could have cumulatively contributed to reducing survival.…”

Section: Mainmentioning

confidence: 98%

“…While on the one hand intermittent precipitation and periodic drought pose strong selective pressures leading to the evolution of embryonic diapause, an adaptation that enables killifish to survive in absence of water 2, 3 , on the other hand they cause habitat and population fragmentation, promoting genetic drift. The co-occurrence of strong selective pressure for early-life and extensive drift characterizes life history evolution in African annual killifishes 4 .…”

Section: Mainmentioning

confidence: 99%

“…Analysis of population NF414 (intermediate) ( Figure 1a , NF414-Y and NF414-R) and NF303 (wet) ( Figure 1a , blue line) shows population expansion until recent time (∼50k generations ago). To infer the effective population size ( N e ) of the populations, we used the published mutational rate of 2.6321e−9 per base pair per generation for Nothobranchius computed via dated phylogeny 4 and θ Watterson . In line with the decrease in genetic diversity from wet to dry population, we found a decrease in N e estimates (107221.8, 338849.48 and 683693.25 for GNP, NF414 and NF303, respectively; Figure 1b ).…”

Section: Mainmentioning

confidence: 99%

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Intra-Species Differences in Population Size shape Life History and Genome Evolution

Willemsen

Cui

Reichard

et al. 2019

Preprint

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12The evolutionary forces shaping life history trait divergence within species are largely unknown. 13 Killifish (oviparous Cyprinodontiformes) evolved an annual life cycle as an exceptional 14 adaptation to life in arid savannah environments characterized by seasonal water availability. The 15 turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate known to science and 16 displays differences in lifespan among wild populations, representing an ideal natural experiment 17 in the evolution and diversification of life history. Here, by combining genome sequencing and 18 population genetics, we investigate the evolutionary forces shaping lifespan among turquoise 19 killifish populations. We generate an improved reference assembly for the turquoise killifish 20 genome, trace the evolutionary origin of the sex chromosome, and identify genes under strong 21 positive and purifying selection, as well as those evolving neutrally. We find that the shortest-22 lived turquoise killifish populations, which dwell in fragmented and isolated habitats at the outer 23 margin of the geographical range of the species, are characterized by small effective population 24 size and accumulate throughout the genome several small to large-effect deleterious mutations 25 due to genetic drift. The genes most affected by drift in the shortest-lived turquoise killifish 26 populations are involved in the WNT signalling pathway, neurodegenerative disorders, cancer 27 and the mTOR pathway. As the populations under stronger genetic drift are the shortest-lived 28 ones, we propose that limited population size due to habitat fragmentation and repeated 29 population bottlenecks, by causing the genome-wide accumulation of deleterious mutations, 30 cumulatively contribute to the short adult lifespan in turquoise killifish populations. 31 3 Main 32Killifish are a highly successful teleost group, dwelling in a range of diverse habitats and, 33 uniquely among teleosts, evolved an annual life cycle to survive in arid climates characterized by 34 cycles of rainfalls and drought 1 . While on the one hand intermittent precipitation and periodic 35 drought pose strong selective pressures leading to the evolution of embryonic diapause, an 36 adaptation that enables killifish to survive in absence of water 2,3 , on the other hand they cause 37 habitat and population fragmentation, promoting genetic drift. The co-occurrence of strong 38 selective pressure for early-life and extensive drift characterizes life history evolution in African 39 annual killifishes 4 . 40The turquoise killifish (Nothobranchius furzeri) is the shortest-lived vertebrate with a thoroughly 41 documented a post-embryonic life, which, in the shortest-lived strains, amounts to four 42 months 2,3,5,6 . Turquoise killifish has recently emerged as a powerful new laboratory model to 43 study experimental biology of aging due to its short lifespan and to its wide range of aging-44 related changes, which include neoplasias 7 , decreased regenerative capacity 8 , cel...

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Section: Methodsmentioning

confidence: 99%

Section: Mainmentioning

confidence: 98%

Section: Mainmentioning

confidence: 99%

Section: Mainmentioning

confidence: 99%

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Intra-Species Differences in Population Size shape Life History and Genome Evolution

Willemsen

Cui

Reichard

et al. 2019

Preprint

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“…The killifish is a newly co-opted vertebrate model for aging studies, due to its exceptionally short lifespan (Cellerino et al, 2016;. Recent studies are beginning to explore causal factors of its accelerated aging, including in the brain Cui et al, 2019;Tozzini et al, 2012;Ripa et al, 2017;Matsui et al, 2019). The fast ageing in N.furzeri is hypothesized by some authors to be a trade-off to rapid larval and juvenile growth, but this lead remains mechanistically unexplored (Reichard and Polačik, 2019).…”

Section: Discussionmentioning

confidence: 99%

Mosaic heterochrony in neural progenitors sustains accelerated brain growth and neurogenesis in the juvenile killifish N. furzeri

Coolen

Labusch

Mannioui

et al. 2019

Preprint

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While developmental mechanisms driving increase in brain size during vertebrate evolution are actively studied, we know less of evolutionary strategies allowing to boost brain growth speed. In zebrafish and other vertebrates studied to date, radial glia (RG) constitute the primary neurogenic progenitor population throughout life (Kriegstein and Alvarez-Buylla, 2009); thus, RG activity is a determining factor of growth speed. Here, we ask whether enhanced RG activity is the mechanism selected to drive explosive growth, in adaptation to an ephemeral habitat. In post-hatching larvae of the turquoise killifish, which display drastic developmental acceleration, we show that the dorsal telencephalon (pallium) grows three times faster than in zebrafish. Rather than resulting from enhanced RG activity, we demonstrate that pallial growth is the product of a second type of progenitors (that we term AP for apical progenitors) that actively sustains neurogenesis and germinal zone self-renewal. Intriguingly, AP appear to retain, at larval stages, features of early embryonic progenitors. In parallel, RG enter premature quiescence and express markers of astroglial function. Together, we propose that mosaic heterochrony within the neural progenitor population may permit rapid pallial growth by safeguarding both continued neurogenesis and astroglial function.

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General Characteristics and Properties of Organic Life

Knoflacher

2024

Relativity of Evolution

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Relaxed Selection Limits Lifespan by Increasing Mutation Load

Cited by 111 publications

References 140 publications

Intra-Species Differences in Population Size shape Life History and Genome Evolution

Intra-Species Differences in Population Size shape Life History and Genome Evolution

Mosaic heterochrony in neural progenitors sustains accelerated brain growth and neurogenesis in the juvenile killifish N. furzeri

General Characteristics and Properties of Organic Life

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