Biology subjects

Thornton, K. R.

Publications and source records attributed to Thornton, K. R..

3 recordsLinked to original sources

bioRxiv2023

Multiple sources of uncertainty confound inference of historical human generation times

WO_SCPLOWANGC_SCPLOW et al. (2023) recently proposed an approach to infer the history of human generation intervals from changes in mutation profiles over time. As the relative proportions of different mutation types depend on the ages of parents, binning variants by the time they arose allows for the inference of average paternal and maternal generation intervals over times. Applying this approach to published allele age estimates, WO_SCPLOWANGC_SCPLOW et al. (2023) inferred long-lasting sex differences in average generation times and surprisingly found that ancestral generation times of West African populations remained substantially higher than those of Eurasian populations extending tens of thousands of generations into the past. Here we argue that the results and interpretations in WO_SCPLOWANGC_SCPLOW et al. (2023) are primarily driven by noise and biases in input data and a lack of validation using independent approaches for estimating allele ages. With the recent development of methods to reconstruct genome-wide gene genealogies, coalescence times, and allele ages, we caution that downstream analyses may be strongly influenced by uncharacterized biases in their output.

evolutionary biology↗

bioRxiv2018

Polygenic adaptation to an environmental shift: temporal dynamics of variation under Gaussian stabilizing selection and additive effects on a single trait

Predictions about the effect of natural selection on patterns of linked neutral variation are largely based on models involving the rapid fixation of unconditionally beneficial mutations. However, when phenotypes adapt to a new optimum trait value, the strength of selection on individual mutations decreases as the population adapts. Here, I use explicit forward simulations of a single trait with additive-effect mutations adapting to an optimum shift. Detectable \"hitch-hiking\" patterns are only apparent if i. the optimum shifts are large with respect to equilibrium variation for the trait, ii. mutation rates to large-effect mutations are low, and iii., large-effect mutations rapidly increase in frequency and eventually reach fixation, which typically occurs after the population reaches the new optimum. For the parameters simulated here, partial sweeps do not appreciably affect patterns of linked variation, even when the mutations are strongly selected. The contribution of new mutations versus standing variation to fixation depends on the mutation rate affecting trait values. Given the fixation of a strongly-selected variant, patterns of hitch-hiking are similar on average for the two classes of sweeps because sweeps from standing variation involving large-effect mutations are rare when the optimum shifts. The distribution of effect sizes of new mutations has little effect on the time to reach the new optimum, but reducing the mutational variance increases the magnitude of hitch-hiking patterns. In general, populations reach the new optimum prior to the completion of any sweeps, and the times to fixation are longer for this model than for standard models of directional selection. The long fixation times are due to a combination of declining selection pressures during adaptation and the possibility of interference among weakly selected sites for traits with high mutation rates.

evolutionary biology↗

bioRxiv2016

Tandem duplications lead to novel expression patterns through exon shuffling in D. yakuba

One common hypothesis to explain the impacts of tandem duplications is that whole gene duplications commonly produce additive changes in gene expression due to copy number changes. Here, we use genome wide RNA-seq data from a population sample of Drosophila yakuba to test this gene dosage hypothesis. We observe little evidence of expression changes in response to whole transcript duplication capturing 5' and 3' UTRs. Among whole gene duplications, we observe evidence that dosage sharing across copies is likely to be common. The lack of expression changes after whole gene duplication suggests that the majority of genes are subject to tight regulatory control and therefore not sensitive to changes in gene copy number. Rather, we observe changes in expression level due to both shuffling of regulatory elements and the creation of chimeric structures via tandem duplication. Additionally, we observe 30 de novo gene structures arising from tandem duplications, 23 of which form with expression in the testes. Thus, the value of tandem duplications is likely to be more intricate than simple changes in gene dosage. The common regulatory effects from chimeric gene formation after tandem duplication may explain their contribution to genome evolution.\n\nAuthor SummaryThe enclosed work shows that whole gene duplications rarely affect gene expression, in contrast to widely held views that the adaptive value of duplicate genes is related to additive changes in gene expression due to gene copy number. We further explain how tandem duplications that create shuffled gene structures can force upregulation of gene sequences, de novo gene creation, and multifold changes in transcript levels.\n\nThese results show that tandem duplications can produce new genes that are a source of immediate novelty associated with more extreme expression changes than previously suggested by theory. Further, these gene expression changes are a potential source of both beneficial and pathogenic mutations, immediately relevant to clinical and medical genetics in humans and other metazoans.

evolutionary biology↗