The mutation rate in human evolution and demographic inference.

The germline mutation rate has long been a major source of uncertainty in human evolutionary and demographic analyses based on genetic data, but estimates have improved substantially in recent years. I discuss our current knowledge of the mutation rate in humans and the underlying biological factors affecting it, which include generation time, parental age and other developmental and reproductive timescales. There is good evidence for a slowdown in mean mutation rate during great ape evolution, but not for a more recent change within the timescale of human genetic diversity. Hence, pending evidence to the contrary, it is reasonable to use a present-day rate of approximately 0.5×10-9bp-1year-1 in all human or hominin demographic analyses.Isaac Newton Trust/Wellcome Trust ISSF Joint Research Grant.This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Elsevier

What is ancestry?

Ancestry connects genetics and society in fundamental ways. For many people it has cultural, religious or even political significance, and can play a key role in shaping personal and public identities. People’s desire to discover their own ancestry drives the multibillion-dollar genealogy industry, which has grown rapidly in the era of consumer genomics. Companies such as 23andMe and Ancestry now claim tens of millions of customers worldwide. In parallel, our scientific understanding of the human past is being transformed by studies of ancient and modern genetic data, which allow us to track changes in ancestry over space and time. Sophisticated methods have been developed to infer and visualise these relationships. Thus, it seems that both scientists and the wider public are learning more and more about ancestry, and there is an optimistic sense that genetic data provide an exhaustive repository of ancestral information

Mutation rates and the evolution of germline structure

This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Royal Society Publishing.Genome sequencing studies of de novo mutations in humans have revealed surprising incongruities with our understanding of human germline mutation. In particular, the mutation rate observed in modern humans is substantially lower than that estimated from calibration against the fossil record, and the paternal age effect in mutations transmitted to offspring is much weaker than expected from our longstanding model of spermatogenesis. I consider possible explanations for these discrepancies, including evolutionary changes in life history parameters such as generation time and the age of puberty, a possible contribution from undetected post-zygotic mutations early in embryo development, and changes in cellular mutation processes at different stages of the germline. I suggest a revised model of stem cell state transitions during spermatogenesis, in which ‘dark’ gonial stem cells play a more active role than hitherto envisaged, with a long cycle time undetected in experimental observations. More generally I argue that the mutation rate and its evolution depend intimately on the structure of the germline in humans and other primates.I am grateful for support from an Isaac Newton Trust/ Wellcome Trust ISSF Joint Research Grant

Destruction of protoplanetary disks in the Orion Nebula Cluster

We use numerical N-body simulations of the Orion Nebula Cluster (ONC) to investigate the destruction of protoplanetary disks by close stellar encounters and UV radiation from massive stars. The simulations model a cluster of 4000 stars, and we consider separately cases in which the disks have fixed radii of 100 AU and 10 AU. In the former case, depending on a star's position and orbit in the cluster over 10^7 years, UV photoevaporation removes at least 0.01 Msol from its disk, and can remove up to 1 Msol. We find no dynamical models of the ONC consistent with the suggestion of Storzer and Hollenbach that the observed distribution and abundance of proplyds could be explained by a population of stars on radial orbits which spend relatively little time near Theta 1C Ori (the most massive star in the ONC). Instead the observations require either massive disks (e.g. a typical initial disk mass of 0.4 Msol) or a very recent birth for Theta 1C Ori. When we consider the photoevaporation of the inner 10 AU of disks in the ONC, we find that planet formation would be hardly affected. Outside that region, planets would be prevented from forming in about half the systems, unless either the initial disk masses were very high or they formed in less than ~ 2 Myr and Theta 1C Ori has only very recently appeared. We also present statistics on the distribution of minimum stellar encounter separations. This peaks at 1000 AU, with less than 10% of stars having had an encounter closer than 100 AU after 10^7 years. We conclude that stellar encounters are unlikely to play a significant role in destroying protoplanetary disks. In the absence of any disruption mechanism other than those considered here, we would thus predict planetary systems like our own to be common amongst stars forming in ONC-like environments.Comment: 9 pages, 9 figures, to be published in MNRA

Brown dwarf populations in open clusters

We present the results of multiple simulations of open clusters, modelling the dynamics of a population of brown dwarf members. We consider the effects of a large range of primordial binary populations, including the possibilities of having brown dwarf members contained within a binary system. We also examine the effects of various cluster diameters and masses. Our examination of a population of wide binary systems containing brown dwarfs, reveals evidence for exchange reactions whereby the brown dwarf is ejected from the system and replaced by a heavier main-sequence star. We find that there exists the possibility of hiding a large fraction of the brown dwarfs contained within the primordial binary population. We conclude that it is probable that the majority of brown dwarfs are contained within primordial binary systems which then hides a large proportion of them from detection.Comment: 16 pages, 8 figures; to appear in MNRA

Short-range template switching in great ape genomes explored using pair hidden Markov models.

Many complex genomic rearrangements arise through template switch errors, which occur in DNA replication when there is a transient polymerase switch to an alternate template nearby in three-dimensional space. While typically investigated at kilobase-to-megabase scales, the genomic and evolutionary consequences of this mutational process are not well characterised at smaller scales, where they are often interpreted as clusters of independent substitutions, insertions and deletions. Here we present an improved statistical approach using pair hidden Markov models, and use it to detect and describe short-range template switches underlying clusters of mutations in the multi-way alignment of hominid genomes. Using robust statistics derived from evolutionary genomic simulations, we show that template switch events have been widespread in the evolution of the great apes' genomes and provide a parsimonious explanation for the presence of many complex mutation clusters in their phylogenetic context. Larger-scale mechanisms of genome rearrangement are typically associated with structural features around breakpoints, and accordingly we show that atypical patterns of secondary structure formation and DNA bending are present at the initial template switch loci. Our methods improve on previous non-probabilistic approaches for computational detection of template switch mutations, allowing the statistical significance of events to be assessed. By specifying realistic evolutionary parameters based on the genomes and taxa involved, our methods can be readily adapted to other intra- or inter-species comparisons

Detecting archaic introgression using an unadmixed outgroup.

Human populations outside of Africa have experienced at least two bouts of introgression from archaic humans, from Neanderthals and Denisovans. In Papuans there is prior evidence of both these introgressions. Here we present a new approach to detect segments of individual genomes of archaic origin without using an archaic reference genome. The approach is based on a hidden Markov model that identifies genomic regions with a high density of single nucleotide variants (SNVs) not seen in unadmixed populations. We show using simulations that this provides a powerful approach to identifying segments of archaic introgression with a low rate of false detection, given data from a suitable outgroup population is available, without the archaic introgression but containing a majority of the variation that arose since initial separation from the archaic lineage. Furthermore our approach is able to infer admixture proportions and the times both of admixture and of initial divergence between the human and archaic populations. We apply the model to detect archaic introgression in 89 Papuans and show how the identified segments can be assigned to likely Neanderthal or Denisovan origin. We report more Denisovan admixture than previous studies and find a shift in size distribution of fragments of Neanderthal and Denisovan origin that is compatible with a difference in admixture time. Furthermore, we identify small amounts of Denisova ancestry in South East Asians and South Asians

Genomes reveal marked differences in the adaptive evolution between orangutan species

Integrating demography and adaptive evolution is pivotal to understanding the evolutionary history and conservation of great apes. However, little is known about the adaptive evolution of our closest relatives, in particular if and to what extent adaptions to environmental differences have occurred. Here, we used whole-genome sequencing data from critically endangered orangutans from North Sumatra (Pongo abelii) and Borneo (P. pygmaeus) to investigate adaptive responses of each species to environmental differences during the Pleistocene