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The distribution of fitness effects (DFE) is central to many questions in evolutionary biology. However, little is known about the differences in DFE between closely related species. We use .9000 coding genes orthologous one-to-one across great apes, gibbons, and macaques to assess the stability of the DFE across great apes. We use the unfolded site frequency spectrum of polymorphic mutations (n = 8 haploid chromosomes per population) to estimate the DFE. We find that the shape of the deleterious DFE is strikingly similar across great apes. We confirm that effective population size (N e) is a strong predictor of the strength of negative selection, consistent with the nearly neutral theory. However, we also find that the strength of negative selection varies more than expected given the differences in N e between species. Across species, mean fitness effects of new deleterious mutations covaries with N e , consistent with positive epistasis among deleterious mutations. We find that the strength of negative selection for the smallest populations, bonobos and western chimpanzees, is higher than expected given their N e. This may result from a more efficient purging of strongly deleterious recessive variants in these populations. Forward simulations confirm that these findings are not artifacts of the way we are inferring N e and DFE parameters. All findings are replicated using only GC-conservative mutations, thereby confirming that GC-biased gene conversion is not affecting our conclusions.

Ampliconic genes are multicopy genes often located on sex chromosomes and enriched for testis-expressed genes. Here, Lucotte et al. developed new bioinformatic approaches to investigate the ampliconic gene copy number and their coding...

1Ampliconic genes are good candidates for speciation genes: they are testis-2 expressed, multicopy and localized on sex chromosomes. Moreover, copy 3 number variation in a specific ampliconic gene pair (Slx and Sly) is involved in 4 hybrid incompatibilities between M. musculus and M. domesticus. However, we 5 know little about the distribution of the ampliconic genes copy number and their 6 turnover in human populations. Here we explore the evolution of human X-and 7

The distribution of fitness effects (DFE) is central to many questions in evolutionary biology.However, little is known about the differences in DFEs between closely related species. We use more than 9,000 coding genes orthologous onetoone across great apes, gibbons, and macaques to assess the stability of the DFE across great apes. We use the unfolded site frequency spectrum of polymorphic mutations (n = 8 haploid chromosomes per population) to estimate the DFE. We find that the shape of the deleterious DFE is strikingly similar across great apes. We confirm that effective population size (N e ) is a strong predictor of the strength of negative selection, consistent with the Nearly Neutral Theory.However, we also find that the strength of negative selection varies more than expected given the differences in N e between species. Across species, mean fitness effects of new deleterious mutations co varies with N e , consistent with positive epistasis among deleterious mutations. We find that the strength of negative selection for the smallest populations: bonobos and western chimpanzees, is higher than expected given their N e . This may result from a more efficient purging of strongly deleterious recessive variants in these populations. Forward simulations confirm that these findings are not artifacts of the way we are inferring N e and DFE parameters. All findings are replicated using only GCconservative mutations, thereby confirming that GCbiased gene conversion is not affecting our conclusions. 2 4 6 8 10 12 14 16All organisms undergo mutation. Studying the effect of mutations on fitness is fundamental to explain the patterns of genetic diversity within and between species and to predict the impact of population size on the probability of survival, or extinction of a species . The fitness effects of all new mutations that can occur in a given genome are described by the distribution of fitness effects (DFE). The allele frequency distributions or the site frequency spectrum (SFS) contains information to infer the DFE of new mutations. Current statistical methods infer the DFE while accounting for demography and other sources of distortion in the SFS (EyreWalker et al. 2006;Keightley and EyreWalker 2007;Boyko et al. 2008;Schneider et al. 2011;Galtier 2016;Kim et al. 2017;Tataru et al. 2017;Barton and Zeng 2018).The DFE of new deleterious amino acid mutations is assumed to be similar in closely related species, while the mean effect of those deleterious mutations (S d = 2N e s d ) is expected to increase as a function of the effective population size (N e ) (Kimura 1983; Ohta 1992). Very little is known about the variability in the DFE of new beneficial mutations across species as well as how this variability affects the estimates of the deleterious DFE. Most studies have described the DFE of new deleterious mutations of individual populations, while the study of the differences in the DFE between populations or species has remained unexplored. To our knowledge, Huber et al. (2017) is the first work that tries to ...

After the main Out-of-Africa event, humans interbred with Neanderthals leaving 1–2% of Neanderthal DNA scattered in small fragments in all non-African genomes today. Here we investigate what can be learned about human demographic processes from the size distribution of these fragments. We observe differences in fragment length across Eurasia with 12% longer fragments in East Asians than West Eurasians. Comparisons between extant populations with ancient samples show that these differences are caused by different rates of decay in length by recombination since the Neanderthal admixture. In concordance, we observe a strong correlation between the average fragment length and the mutation accumulation, similar to what is expected by changing the ages at reproduction as estimated from trio studies. Altogether, our results suggest differences in the generation interval across Eurasia, by up 10–20%, over the past 40,000 years. We use sex-specific mutation signatures to infer whether these changes were driven by shifts in either male or female age at reproduction, or both. We also find that previously reported variation in the mutational spectrum may be largely explained by changes to the generation interval. We conclude that Neanderthal fragment lengths provide unique insight into differences among human populations over recent history.

No abstract

The X chromosome in non-African human populations shows less diversity and less Neanderthal introgression than expected under the standard neutral model. We analyzed 162 X chromosomes from human males worldwide and discovered 14 chromosomal regions where haplotypes of several hundred kilobases rapidly rose to high frequencies in non-Africans. These observations cannot be explained by neutral genetic drift in realistic demographic scenarios and are only consistent with partial selective sweeps produced by strong selection. Using an approach for inferring individual Neanderthal-derived haplotypes, which do not rely on an archaic reference genome, we further discover that the swept haplotypes are devoid of the archaic ancestry otherwise typical of the affected chromosomal regions. The ancient Ust'-Ishim male carries its expected proportion of these haplotypes, implying that the sweeps must have occurred between 45,000 and 55,000 years ago. Finally, we find that the chromosomal positions of sweeps overlap previously reported hotspots of selection in great ape evolution. We propose that this puzzling combination of observations points to a general mechanism of positive selection unique to the X chromosome.