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1.  Expression-based segmentation of the Drosophila genome 
BMC Genomics  2013;14:812.
It is generally accepted that gene order in eukaryotes is nonrandom, with adjacent genes often sharing expression patterns across tissues, and that this organization may be important for gene regulation. Here we describe a novel method, based on an explicit probability model instead of correlation analysis, for identifying coordinately expressed gene clusters (‘coexpression segments’), apply it to Drosophila melanogaster, and look for epigenetic associations using publicly available data.
We find that two-thirds of Drosophila genes fall into multigenic coexpression segments, and that such segments are of two main types, housekeeping and tissue-restricted. Consistent with correlation-based studies, we find that adjacent genes within the same segment tend to be physically closer to each other than to the adjacent genes in different segments, and that tissue-restricted segments are enriched for testis-expressed genes. Our segmentation pattern correlates with Hi-C based physical interaction domains, but segments are generally much smaller than domains. Intersegment regions (including those which do not correspond to physical domain boundaries) are enriched for insulator binding sites.
We describe a novel approach for identifying coexpression clusters that does not require arbitrary cutoff values or heuristics, and find that coexpression of adjacent genes is widespread in the Drosophila genome. Coexpression segments appear to reflect a level of regulatory organization related to, but below that of physical interaction domains, and depending in part on insulator binding.
PMCID: PMC3909303  PMID: 24256206
2.  Widespread Genomic Signatures of Natural Selection in Hominid Evolution 
PLoS Genetics  2009;5(5):e1000471.
Selection acting on genomic functional elements can be detected by its indirect effects on population diversity at linked neutral sites. To illuminate the selective forces that shaped hominid evolution, we analyzed the genomic distributions of human polymorphisms and sequence differences among five primate species relative to the locations of conserved sequence features. Neutral sequence diversity in human and ancestral hominid populations is substantially reduced near such features, resulting in a surprisingly large genome average diversity reduction due to selection of 19–26% on the autosomes and 12–40% on the X chromosome. The overall trends are broadly consistent with “background selection” or hitchhiking in ancestral populations acting to remove deleterious variants. Average selection is much stronger on exonic (both protein-coding and untranslated) conserved features than non-exonic features. Long term selection, rather than complex speciation scenarios, explains the large intragenomic variation in human/chimpanzee divergence. Our analyses reveal a dominant role for selection in shaping genomic diversity and divergence patterns, clarify hominid evolution, and provide a baseline for investigating specific selective events.
Author Summary
Comparisons of the human and chimpanzee genomes have revealed that the frequency of sequence differences between these species varies dramatically across the genome. Previously proposed explanations for this variation include a large ancestral population, variable mutation rates, or a complex speciation scenario in which humans and chimpanzees initially separated but then rehybridyzed several million years later. We consider, here, an alternate possibility; the action of selection to remove less-fit functional variants from a population has significantly reduced the frequency of “neutral” sequence differences at nearby sites. We identified sequences that are likely to be subject to natural selection because they are highly conserved across placental mammals and showed that neutral differences among five primate species are greatly depleted near such sequences. Applying a theoretical evolutionary model, we found that selection has played a greater role in shaping hominid genome evolution than has been appreciated and provides a better explanation for patterns of sequence differences than other hypotheses.
PMCID: PMC2669884  PMID: 19424416

Results 1-2 (2)