Biology subjects

Huber, C. D.

Publications and source records attributed to Huber, C. D..

21 records · Page 2Linked to original sources

bioRxiv2017

A-to-I RNA editing uncovers hidden signals of adaptive genome evolution in animals

In animals, the most common type of RNA editing is the deamination of adenosines (A) into inosines (I). Because inosines base-pair with cytosines (C), they are interpreted as guanosines (G) by the cellular machinery and genomically encoded G alleles at edited sites mimic the function of edited RNAs. The contribution of this hardwiring effect on genome evolution remains obscure. We looked for population genomics signatures of adaptive evolution associated with A-to-I RNA edited sites in humans and Drosophila melanogaster. We found that single nucleotide polymorphisms at edited sites occur 3 (humans) to 15 times (Drosophila) more often than at unedited sites, the nucleotide G is virtually the unique alternative allele at edited sites and G alleles segregate at higher frequency at edited sites than at unedited sites. Our study reveals that coding synonymous and nonsynonymous as well as silent and intergenic A-to-I RNA editing sites are likely adaptive in the distantly related human and Drosophila lineages.

evolutionary biology↗

bioRxiv2017

Deleterious variation mimics signatures of genomic incompatibility and adaptive introgression

While it is appreciated that population size changes can impact patterns of deleterious variation in natural populations, less attention has been paid to how population admixture affects the dynamics of deleterious variation. Here we use population genetic simulations to examine how admixture impacts deleterious variation under a variety of demographic scenarios, dominance coefficients, and recombination rates. Our results show that gene flow between populations can temporarily reduce the genetic load of smaller populations, especially if deleterious mutations are recessive. Additionally, when fitness effects of new mutations are recessive, between-population differences in the sites at which deleterious variants exist creates heterosis in hybrid individuals. This can lead to an increase in introgressed ancestry, particularly when recombination rates are low. Under certain scenarios, introgressed ancestry can increase from an initial frequency of 5% to 30-75% and fix at many loci, even in the absence of beneficial mutations. Further, deleterious variation and admixture can generate correlations between the frequency of introgressed ancestry and recombination rate or exon density, even in the absence of other types of selection. The direction of these correlations is determined by the specific demography and whether mutations are additive or recessive. Therefore, it is essential that null models include both demography and deleterious variation before invoking reproductive incompatibilities or adaptive introgression to explain unusual patterns of genetic variation.

evolutionary biology↗

bioRxiv2017

Gene expression drives the evolution of dominance

Dominance is a fundamental concept in molecular genetics and has implications for understanding patterns of genetic variation, evolution, and complex traits. However, despite its importance, the degree of dominance has yet to be quantified in natural populations. Here, we leverage multiple mating systems in natural populations of Arabidopsis to co-estimate the distribution of fitness effects and dominance coefficients of new amino acid changing mutations. We find that more deleterious mutations are more likely to be recessive than less deleterious mutations. Further, this pattern holds across gene categories, but varies with the connectivity and expression patterns of genes. Our work argues that dominance arose as the inevitable consequence of the functional importance of genes and their optimal expression levels.\n\nOne sentence summaryWe use population genomic data to characterize the degree of dominance for new mutations and develop a new theory for its evolution.

genomics↗