…before returning to the field.
Properties and rates of germline mutations in humans (C.D. Campbell, E.E. Eichler)
Trends in Genetics, 17 May 2013, 10.1016/j.tig.2013.04.005
ABSTRACT: All genetic variation arises via new mutations; therefore, determining the rate and biases for different classes of mutation is essential for understanding the genetics of human disease and evolution. Decades of mutation rate analyses have focused on a relatively small number of loci because of technical limitations. However, advances in sequencing technology have allowed for empirical assessments of genome-wide rates of mutation. Recent studies have shown that 76% of new mutations originate in the paternal lineage and provide unequivocal evidence for an increase in mutation with paternal age. Although most analyses have focused on single nucleotide variants (SNVs), studies have begun to provide insight into the mutation rate for other classes of variation, including copy number variants (CNVs), microsatellites, and mobile element insertions (MEIs). Here, we review the genome-wide analyses for the mutation rate of several types of variants and suggest areas for future research.
Establishing the baseline mutation rate throughout our evolutionary past is hugely important. The mutation rate establishes the “clock” that allows researchers to estimate the dates of key evolutionary events based on genetic data. Prior to readily available genomic data, the rate of mutation was indirectly estimated by looking at divergence data between lineages and fossil-based estimates of divergence time. Since about 2008, an increasing number of studies have attempted to directly measure this value by looking at genomic data in pedigrees (basically, how many de novo mutations arise between parents and offspring?). Since these studies have begun to emerge, a number of different estimates for the human baseline mutation rate have emerged, but most of them share the property that they are considerably slower than older, long-term observations of mutation rates based on fossil calibration.
Of course, mutation rates are not a single, monolithic figure. Different classes of mutations appear to have different rates. Additionally, mothers and fathers do not appear to contribute equally to de novo mutations, with father’s providing the majority of new mutations (an observation predicted by evolutionary theory). The above paper provides a review of a lot of this recent research, with additional commentary on its evolutionary significance.
The piece that remains to be fully explored is how, theoretically and practically, short-term rate estimates connect with long-term rate estimates. The problem for mutation is analogous to the problem for selection (short-term selection rates invariably exceed long-term rates of selection by a large margin). The observation that current short term rates of mutation are considerably slower than estimates of long-term rates is not a rejection of the latter…rather it is simply a different observation. Increasingly, it appears to be an observation that is solid in its groundings. Now the challenge is to figure out how to directly test why the two rates are different, or alternatively, how short-term rates translate to long-term rates.
Barium distributions in teeth reveal early-life dietary transitions in primates (C. Austin, T.M. Smith, A. Bradman, et al.)
Nature (2013) doi:10.1038/nature12169
ABSTRACT: Early-life dietary transitions reflect fundamental aspects of primate evolution and are important determinants of health in contemporary human populations1, 2. Weaning is critical to developmental and reproductive rates; early weaning can have detrimental health effects but enables shorter inter-birth intervals, which influences population growth3. Uncovering early-life dietary history in fossils is hampered by the absence of prospectively validated biomarkers that are not modified during fossilization4. Here we show that large dietary shifts in early life manifest as compositional variations in dental tissues. Teeth from human children and captive macaques, with prospectively recorded diet histories, demonstrate that barium (Ba) distributions accurately reflect dietary transitions from the introduction of mother’s milk through the weaning process. We also document dietary transitions in a Middle Palaeolithic juvenile Neanderthal, which shows a pattern of exclusive breastfeeding for seven months, followed by seven months of supplementation. After this point, Ba levels in enamel returned to baseline prenatal levels, indicating an abrupt cessation of breastfeeding at 1.2 years of age. Integration of Ba spatial distributions and histological mapping of tooth formation enables novel studies of the evolution of human life history, dietary ontogeny in wild primates, and human health investigations through accurate reconstructions of breastfeeding history.
This looks like a cool study. Basically, the authors have found a chemical signal, observable in dental enamel, that distinguishes changes in infant diet. Specifically, they are trying to determine the age at which children move off a breastmilk-exclusive diet and the age at when they move off breastmilk entirely. Evolutionarily, these are important transitions, as they represent important transitions in childhood diet, maternal energetics, and the evolutionary relationship between mother and child. There are theoretical expectations, based on living humans and non-human primates, about when these events should occur, and previous fossil based studies, but the latter have been built upon assumptions not tested in the field. This appears to be a novel and more direct way to address these issues. I also like that the authors do not take their one fossil observation (a Neandertal from Belgium) and run wild with it.
Katie Hinde, one of the co-authors of this study, has more on her blog.
