Description

Genomic scaffolds from 14 Drosophila species are aligned against the D. melanogaster genome assembly (dm6) with LAST using default parameters. The alignments are then processed using the UCSC whole genome alignment protocol (i.e. chaining, netting, and maffing).

PhastCons (which has been used in previous Conservation tracks) is a hidden Markov model-based method that estimates the probability that each nucleotide belongs to a conserved element, based on the multiple alignment. It considers not just each individual alignment column, but also its flanking columns. By contrast, phyloP separately measures conservation at individual columns, ignoring the effects of their neighbors. As a consequence, the phyloP plots have a less smooth appearance than the phastCons plots, with more "texture" at individual sites. The two methods have different strengths and weaknesses. PhastCons is sensitive to "runs" of conserved sites, and is therefore effective for picking out conserved elements. PhyloP, on the other hand, is more appropriate for evaluating signatures of selection at particular nucleotides or classes of nucleotides (e.g., third codon positions, or first positions of miRNA target sites).

Another important difference is that phyloP can measure acceleration (faster evolution than expected under neutral drift) as well as conservation (slower than expected evolution). In the phyloP plots, sites predicted to be conserved are assigned positive scores (and shown in blue), while sites predicted to be fast-evolving are assigned negative scores (and shown in red). The absolute values of the scores represent -log p-values under a null hypothesis of neutral evolution. The phastCons scores, by contrast, represent probabilities of negative selection and range between 0 and 1.

Both phastCons and phyloP treat alignment gaps and unaligned nucleotides as missing data. Missing sequence in the assemblies is highlighted in the track display by regions of yellow when zoomed out and Ns displayed at base level (see Gap Annotation, below).

References

PhyloP

Cooper GM, Stone EA, Asimenos G; NISC Comparative Sequencing Program, Green ED, Batzoglou S, Sidow A. Distribution and intensity of constraint in mammalian genomic sequence . Genome Res. 2005 Jul;15(7):901-13.

Chain/Net

Kent WJ, Baertsch R, Hinrichs A, Miller W, and Haussler D. Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes. Proc Natl Acad Sci USA 2003 100(20): 11484-11489.

Multiz

Blanchette M, Kent WJ, Riemer C, Elnitski L, Smit AFA, Roskin KM, Baertsch R, Rosenbloom K, Clawson H, Green ED, Haussler D, Miller W. Aligning multiple genomic sequences with the threaded blockset aligner. Genome Res. 2004 14(4):708-715.

LAST

Kielbasa SM, Wan R, Sato K, Horton P, Frith MC. Adaptive seeds tame genomic sequence comparison. Genome Res. 2011 Mar;21(3):487-93.