Description

These tracks show regions of unusual conservation in human relative to other organisms:

• Ultraconserved elements (UCE aka ultras):
  Elements with 100% identity in human/mouse/rat alignments. Many of these were tested in mice, see the VISTA enhancers track in the Regulation track group. (Bejerano et al., Science 2004)
• Human Accelerated Regions (HARs):
  2,649 regions conserved throughout vertebrate evolution but strikingly different in humans (Pollard et al., Nature 2006). This extended list was collected by the Katie Pollard lab from various publications (Capra et al., PTRSB 2013).
• High-confidence Zoonomia Human Accelerated Regions (HARs):
  312 HARs from the Zoonomia Alignments (Keough et al. Science, 2023)
• Human Ancestor Quickly Evolved Regions (HAQERs):
  1,580 HAQERs from (Mangan et al., Cell 2023)
• Human-specific long deletions (hCondels) between human, macaque and chimpanzee:
  583 regions (one not lifted) present in macaque and chimp, but not in humans. Since these are sequences absent from the human genome, we show the 2bp around the deletion. (McLean et al., Nature 2011)
• Short hCondels < 40bp in primates and up to 11 vertebrates:
  43,588 regions deleted in human but present in 11 vertebrates or primates. These regions were tested in an MPRA screen, the MPRA results are in the track and shown when clicking an element. Since the track is showing MPRA results and the position of deletions, what is shown in the track are regions ±100bp around the deletion site on the human genome, not just the two basepairs flanking the site of the deletion. (Xue et al., Science 2023)
• Zoonomia Ultraconserved elements (zooUCEs):
  4,552 Ultraconserved elements identified from the 241-mammals genome alignment. All regions >=20bp where at least 235 species aligned and all aligning species are fixed for the same base at every position. 20-190 bp.
• Zoonomia: Runs of contiguous constraint (RoCCs):
  All genomic regions where contiguous bases have a phyloP score > 2.270 (5% FDR) and are therefore under high constraint. Regions separated by a single base with phyloP < 2.270 were merged. N = 595,535; 20-1,359 bp.
• Zoonomia: Unannotated Intergenic Constrained Regions (UNICORNs):
  Non-coding regions of the genome that lack annotation in ENCODE3 but show high evolutionary constraint, suggesting function. Positions with phyloP > 2.270 (5% FDR) within 5bp of each other are grouped into UNICORNs. N = 424,180; 11 - 1,325 bp.
• UCNEBase: Elements conserved with chicken:
  Non-coding elements > 200 bp long and 95% conserved between human and chicken. (Dimitrieva and Bucher, NAR 2013)
• UCNEBase: Elements paralogous to others:
  Alignable with E<10^-4 to other chicken-conserved elements.
• UCNEBase UGRBs: Ultra-conserved genomic regulatory blocks:
  Chicken-conserved elements within 0.5 Mb in both human and chicken.

Display Conventions and Configuration

All tracks show the locations and name for the features. Only one, Short hCondels, has MPRA test results in the track itself.

Methods

Ultraconserved sequences: downloaded from our hg19 public track hub and lifted to hg38.

HARs: Downloaded from https://docpollard.org/research/. Converted from Excel. Lifted 2649 HAR file to hg38.

HAQERs: Converted from supplemental table 1 of Mangan et al, Cell 2023.

Long hCondels from McLean: Excel file converted manually as supplement 2 from https://pmc.ncbi.nlm.nih.gov/articles/PMC3071156/ and lifted to hg38 from hg18.

Short hCondels from Xue et al: Excel file converted manually from supplemental file 1. From the paper: "We constructed a chimpanzee-anchored multiple sequence alignment across 11 vertebrate species to detect statistically significant conserved sequences (1,371,766). These elements ranged from being deeply conserved throughout vertebrates to being conserved only through primates. We then intersected our conserved elements with called deletions (2,042,706) between the human (hg38) and chimpanzee (panTro4) genomes to yield 43,588 putative hCONDELs."

Zoonomia UNICORNs, ZooUCEs and RoCCs: Downloaded from https://cgl.gi.ucsc.edu/data/cactus/zoonomia-2021-track-hub/hg38/

Credits

Thanks to Katie Pollard, Hiram Clawson, James Xue, Matt Christmas (matthew.christmas@imbim.uu.se), and Mark Diekhans for providing the data.

References

Bejerano G, Pheasant M, Makunin I, Stephen S, Kent WJ, Mattick JS, Haussler D. Ultraconserved elements in the human genome. Science. 2004 May 28;304(5675):1321-5. PMID: 15131266

Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A et al. An RNA gene expressed during cortical development evolved rapidly in humans. Nature. 2006 Sep 14;443(7108):167-72. PMID: 16915236

Keough KC, Whalen S, Inoue F, Przytycki PF, Fair T, Deng C, Steyert M, Ryu H, Lindblad-Toh K, Karlsson E et al. Three-dimensional genome rewiring in loci with human accelerated regions. Science. 2023 Apr 28;380(6643):eabm1696. PMID: 37104607; PMC: PMC10999243

Mangan RJ, Alsina FC, Mosti F, Sotelo-Fonseca JE, Snellings DA, Au EH, Carvalho J, Sathyan L, Johnson GD, Reddy TE et al. Adaptive sequence divergence forged new neurodevelopmental enhancers in humans. Cell. 2022 Nov 23;185(24):4587-4603.e23. PMID: 36423581; PMC: PMC10013929

McLean CY, Reno PL, Pollen AA, Bassan AI, Capellini TD, Guenther C, Indjeian VB, Lim X, Menke DB, Schaar BT et al. Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature. 2011 Mar 10;471(7337):216-9. PMID: 21390129; PMC: PMC3071156

Xue JR, Mackay-Smith A, Mouri K, Garcia MF, Dong MX, Akers JF, Noble M, Li X, Zoonomia Consortium, Lindblad-Toh K et al. The functional and evolutionary impacts of human-specific deletions in conserved elements. Science. 2023 Apr 28;380(6643):eabn2253. PMID: 37104592; PMC: PMC10202372

Dimitrieva S, Bucher P. UCNEbase--a database of ultraconserved non-coding elements and genomic regulatory blocks. Nucleic Acids Res. 2013 Jan;41(Database issue):D101-9. PMID: 23193254; PMC: PMC3531063