Human accelerated regions

Last updated

Human accelerated regions (HARs), first described in August 2006, [1] [2] are a set of 49 segments of the human genome that are conserved throughout vertebrate evolution but are strikingly different in humans. They are named according to their degree of difference between humans and chimpanzees (HAR1 showing the largest degree of human-chimpanzee differences). Found by scanning through genomic databases of multiple species, some of these highly mutated areas may contribute to human-specific traits. Others may represent loss of functional mutations, possibly due to the action of biased gene conversion [2] [3] rather than adaptive evolution. [4] [5] [6]

Contents

Characterisation of HAR1-HAR5 regions, from a paper on Forces shaping the fastest evolving regions in the human genome by Katherine Pollard et al. Details of HAR1-HAR5 journal.pgen.0020168.t001.png
Characterisation of HAR1-HAR5 regions, from a paper on Forces shaping the fastest evolving regions in the human genome by Katherine Pollard et al.

Several of the HARs encompass genes known to produce proteins important in neurodevelopment. HAR1 is a 106-base pair stretch found on the long arm of chromosome 20 overlapping with part of the RNA genes HAR1F and HAR1R. HAR1F is active in the developing human brain. The HAR1 sequence is found (and conserved) in chickens and chimpanzees but is not present in fish or frogs that have been studied. There are 18 base pair mutations different between humans and chimpanzees, far more than expected by its history of conservation. [1]

HAR2 includes HACNS1 a gene enhancer "that may have contributed to the evolution of the uniquely opposable human thumb, and possibly also modifications in the ankle or foot that allow humans to walk on two legs". Evidence to date shows that of the 110,000 gene enhancer sequences identified in the human genome, HACNS1 has undergone the most change during the evolution of humans following the split with the ancestors of chimpanzees. [7] The substitutions in HAR2 may have resulted in loss of binding sites for a repressor, possibly due to biased gene conversion. [8] [9]

HAR genes

See also

Related Research Articles

Molecular evolution is the process of change in the sequence composition of cellular molecules such as DNA, RNA, and proteins across generations. The field of molecular evolution uses principles of evolutionary biology and population genetics to explain patterns in these changes. Major topics in molecular evolution concern the rates and impacts of single nucleotide changes, neutral evolution vs. natural selection, origins of new genes, the genetic nature of complex traits, the genetic basis of speciation, the evolution of development, and ways that evolutionary forces influence genomic and phenotypic changes.

<span class="mw-page-title-main">Ribosomal DNA</span>

Ribosomal DNA (rDNA) is a DNA sequence that codes for ribosomal RNA. These sequences regulate transcription initiation and amplification, and contain both transcribed and non-transcribed spacer segments.

Gene conversion is the process by which one DNA sequence replaces a homologous sequence such that the sequences become identical after the conversion event. Gene conversion can be either allelic, meaning that one allele of the same gene replaces another allele, or ectopic, meaning that one paralogous DNA sequence converts another.

<span class="mw-page-title-main">Conserved sequence</span> Similar DNA, RNA or protein sequences within genomes or among species

In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids or proteins across species, or within a genome, or between donor and receptor taxa. Conservation indicates that a sequence has been maintained by natural selection.

<span class="mw-page-title-main">Human accelerated region 1</span>

In molecular biology, Human Accelerated Region 1 is a segment of the human genome found on the long arm of chromosome 20. It is a human accelerated region. It is located within a pair of overlapping long non-coding RNA genes, HAR1A (HAR1F) and HAR1B (HAR1R).

Human evolutionary genetics studies how one human genome differs from another human genome, the evolutionary past that gave rise to the human genome, and its current effects. Differences between genomes have anthropological, medical, historical and forensic implications and applications. Genetic data can provide important insights into human evolution.

<span class="mw-page-title-main">MAD1L1</span> Protein-coding gene in the species Homo sapiens

Mitotic spindle assembly checkpoint protein MAD1 is a protein that in humans is encoded by the MAD1L1 gene.

<span class="mw-page-title-main">NPAS3</span> Protein-coding gene in the species Homo sapiens

NPAS3 or Neuronal PAS domain protein 3 is a brain-enriched transcription factor belonging to the bHLH-PAS superfamily of transcription factors, the members of which carry out diverse functions, including circadian oscillations, neurogenesis, toxin metabolism, hypoxia, and tracheal development. NPAS3 contains basic helix-loop-helix structural motif and PAS domain, like the other proteins in the superfamily.

<span class="mw-page-title-main">David Haussler</span> American bioinformatician

David Haussler is an American bioinformatician known for his work leading the team that assembled the first human genome sequence in the race to complete the Human Genome Project and subsequently for comparative genome analysis that deepens understanding the molecular function and evolution of the genome.

<span class="mw-page-title-main">FHIT</span> Protein-coding gene in the species Homo sapiens

Bis(5'-adenosyl)-triphosphatase also known as fragile histidine triad protein (FHIT) is an enzyme that in humans is encoded by the FHIT gene.

<span class="mw-page-title-main">WWOX</span> Protein-coding gene in the species Homo sapiens

WW domain-containing oxidoreductase is an enzyme that in humans is encoded by the WWOX gene.

<span class="mw-page-title-main">PTPRT</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the PTPRT gene.

<span class="mw-page-title-main">CENTG2</span> Protein-coding gene in the species Homo sapiens

Arf-GAP with GTPase, ANK repeat and PH domain-containing protein 1 is an enzyme that in humans is encoded by the AGAP1 gene.

Adaptive evolution results from the propagation of advantageous mutations through positive selection. This is the modern synthesis of the process which Darwin and Wallace originally identified as the mechanism of evolution. However, in the last half century, there has been considerable debate as to whether evolutionary changes at the molecular level are largely driven by natural selection or random genetic drift. Unsurprisingly, the forces which drive evolutionary changes in our own species’ lineage have been of particular interest. Quantifying adaptive evolution in the human genome gives insights into our own evolutionary history and helps to resolve this neutralist-selectionist debate. Identifying specific regions of the human genome that show evidence of adaptive evolution helps us find functionally significant genes, including genes important for human health, such as those associated with diseases.

A conserved non-coding sequence (CNS) is a DNA sequence of noncoding DNA that is evolutionarily conserved. These sequences are of interest for their potential to regulate gene production.

TUC338 is an ultra-conserved element which is transcribed to give a non-coding RNA. The TUC338 gene was first identified as uc.338, along with 480 other ultra-conserved elements in the human genome. Expression of this RNA gene has been found to dramatically increase in hepatocellular carcinoma (HCC) cells.

hCONDELs refer to regions of deletions within the human genome containing sequences that are highly conserved among closely related relatives. Almost all of these deletions fall within regions that perform non-coding functions. These represent a new class of regulatory sequences and may have played an important role in the development of specific traits and behavior that distinguish closely related organisms from each other.

Adam C. Siepel is an American computational biologist known for his research in comparative genomics and population genetics, particularly the development of statistical methods and software tools for identifying evolutionarily conserved sequences. Siepel is currently Chair of the Simons Center for Quantitative Biology and Professor in the Watson School for Biological Sciences at Cold Spring Harbor Laboratory.

Mutation bias is a pattern in which some type of mutation occurs more often than expected under uniformity. The types are most often defined by the molecular nature of the mutational change, but sometimes they are based on downstream effects, e.g., Ostrow, et al.

Katherine Snowden Pollard is the Director of the Gladstone Institute of Data Science and Biotechnology and a professor at the University of California, San Francisco (UCSF). She is a Chan Zuckerberg Biohub Investigator. She was awarded Fellowship of the International Society for Computational Biology in 2020 and the American Institute for Medical and Biological Engineering in 2021 for outstanding contributions to computational biology and bioinformatics.

References

  1. 1 2 Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M Jr, Vanderhaeghen P, Haussler D (2006-08-16). "An RNA gene expressed during cortical development evolved rapidly in humans" (PDF). Nature. 443 (7108): 167–172. Bibcode:2006Natur.443..167P. doi:10.1038/nature05113. PMID   16915236. S2CID   18107797. supplement
  2. 1 2 3 Pollard KS, Salama SR, King B, Kern AD, Dreszer T, Katzman S, Siepel A, Pedersen JS, Bejerano G, Baertsch R, Rosenbloom KR, Kent J, Haussler D (October 2006). "Forces shaping the fastest evolving regions in the human genome". PLoS Genet. 2 (10): e168. doi: 10.1371/journal.pgen.0020168 . PMC   1599772 . PMID   17040131.
  3. Kostka D, Hubisz MJ, Siepel A, Pollard KS (March 2012). "The role of GC-biased gene conversion in shaping the fastest evolving regions of the human genome". Mol. Biol. Evol. 29 (3): 1047–57. doi:10.1093/molbev/msr279. PMC   3278478 . PMID   22075116.
  4. Pollard, Katherine (2009). "What Makes Us Human?". Scientific American . 300 (5): 44–49. Bibcode:2009SciAm.300e..44P. doi:10.1038/scientificamerican0509-44. PMID   19438048.
  5. Scientists Identify Gene Difference Between Humans and Chimps, Scientific American , 17 August 2006
  6. Researchers Identify Human DNA on the Fast Track, Howard Hughes Medical Institute website, 16 August 2006.
  7. "HACNS1: Gene enhancer in evolution of human opposable thumb". Science Codex. September 4, 2008. Retrieved May 17, 2010.
  8. "Loss-of-Function Mutation in a Repressor Module of Human-Specifically Activated Enhancer HACNS1". Molecular Biology and Evolution. September 22, 2011. Archived from the original on April 15, 2013.
  9. Zimov, S. (February 6, 2009). "Comment on "Human-Specific Gain of Function in a Developmental Enhancer"". Science. 323 (5915): 714–5, author reply 714-5. doi:10.1126/science.323.5915.714a. PMID   19197041. S2CID   31587069.