Showing papers by "Hernán A. Burbano published in 2012"

Analysis of human accelerated DNA regions using archaic hominin genomes.

Abstract: Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations.

Transcription Factors Are Targeted by Differentially Expressed miRNAs in Primates

Abstract: MicroRNAs (miRNAs) are small RNA molecules involved in the regulation of mammalian gene expression. Together with other transcription regulators, miRNAs modulate the expression of genes and thereby potentially contribute to tissue and species diversity. To identify miRNAs that are differentially expressed between tissues and/or species, and the genes regulated by these, we have quantified expression of miRNAs and messenger RNAs in five tissues from multiple human, chimpanzee, and rhesus macaque individuals using high-throughput sequencing. The breadth of this tissue and species data allows us to show that downregulation of target genes by miRNAs is more pronounced between tissues than between species and that downregulation is more pronounced for genes with fewer binding sites for expressed miRNAs. Intriguingly, we find that tissue- and species-specific miRNAs target transcription factor genes (TFs) significantly more often than expected. Through their regulatory effect on transcription factors, miRNAs may therefore exert an indirect influence on a larger proportion of genes than previously thought.

Annotation of primate miRNAs by high throughput sequencing of small RNA libraries

Abstract: In addition to genome sequencing, accurate functional annotation of genomes is required in order to carry out comparative and evolutionary analyses between species. Among primates, the human genome is the most extensively annotated. Human miRNA gene annotation is based on multiple lines of evidence including evidence for expression as well as prediction of the characteristic hairpin structure. In contrast, most miRNA genes in non-human primates are annotated based on homology without any expression evidence. We have sequenced small-RNA libraries from chimpanzee, gorilla, orangutan and rhesus macaque from multiple individuals and tissues. Using patterns of miRNA expression in conjunction with a model of miRNA biogenesis we used these high-throughput sequencing data to identify novel miRNAs in non-human primates. We predicted 47 new miRNAs in chimpanzee, 240 in gorilla, 55 in orangutan and 47 in rhesus macaque. The algorithm we used was able to predict 64% of the previously known miRNAs in chimpanzee, 94% in gorilla, 61% in orangutan and 71% in rhesus macaque. We therefore added evidence for expression in between one and five tissues to miRNAs that were previously annotated based only on homology to human miRNAs. We increased from 60 to 175 the number miRNAs that are located in orthologous regions in humans and the four non-human primate species studied here. In this study we provide expression evidence for homology-based annotated miRNAs and predict de novo miRNAs in four non-human primate species. We increased the number of annotated miRNA genes and provided evidence for their expression in four non-human primates. Similar approaches using different individuals and tissues would improve annotation in non-human primates and allow for further comparative studies in the future.