[author: Kevin E. Noonan]
This week's edition of Nature contains the results of the latest (and last) of the "genome" projects for members of the Homini (humans and their closest primate ancestors): Gorilla gorilla gorilla, the western lowland gorilla (in particular a gorilla named Kamilah, the Craig Venter of her species) (Saclly et al., "Insights into hominid evolution from the gorilla genome sequence," Nature 483: 169-75 (08 March 2012)). Like most of the genome projects, the results reported in Nature merely scratch the surface of the wealth of sequence data produced in the experiments (comprising 54 Gbp conventional Sanger sequencing and 166.8 Gbp of Illumina sequencing).
In the big picture, genetic comparisons with humans and chimpanzees (Pan troglodytes) revealed that the human/chimpanzee branch of the primate lineage diverged about 10 (range: 8.5-12) million years ago; in contrast, comparison of genomes of western and eastern gorilla species provides an estimate of evolutionary divergence about 1.75 million years ago.
The paper details the assumptions used to arrive at these figures, based on an estimate of 0.5 – 0.6 x 10-9 mutations per bp per year in the primate genomes. However, these researchers acknowledge that there is a disconnect between fossil estimates of when the speciation event occurred and the genetic estimate presented here that can only be reconciled by positing changing mutation rates, that may be explained by correlations with larger body mass and lower generation times between the species. The authors concede that alternative scenarios are possible, including the existence of a population bottleneck and a non-allopatric speciation process in the human/chimp/gorilla line.
Turning to the genetic data, "typical" stretchs of "error-free" sequences were found to be about 7.2 kbp long, with errors clustering in repetitive regions. A total of 3,041,976,159 bp were sequenced, with 20,962 protein coding genes, 1553 pseudogenes, and 6,701 RNA genes identified. The researchers detected selection in the area of coding regions in all three species that suppresses mutations, making these regions more similar between the three species than in the rest of the genome(s). Loss-or-gain analysis in autosomes showed an average of ~3-7 Mbp per species, distributed "genome-wide" and also found in orangutangs and more evolutionarily-distant species. These results were consistent in patterns of gene loss; instances of gene gain were consistent with gene duplication. Interestingly, the paper reports that 30% of gorilla genes are closer to either human or chimp that the corresponding human and chimp genes are to each other. In addition, there is evidence for "accelerated evolution" for around 500 genes in parallel between humans, chimps, and gorillas, particularly in genes involved in hearing: "[s]ome [gene] fragments found only in one species overlap coding exons in annotated genes: 6 genes in human, 5 in chimpanzee and 9 in gorilla, the majority being associated with olfactory receptor proteins or other rapidly evolving functions, such as male fertility and immune response." Rapid structural evolution was also detected in the gorilla Y chromosome, something also observed in comparisons between human and chimp Y chromosomal sequences.
Protein alignment over 11,538 ORFs indentified regions of "accelerated evolution" that focused on "enriched for functions associated with sensory perception, particularly in relation to hearing and brain development," including specifically OTOF (Otoferlin, mutations thereof being the cause of neurosensory nonsyndromic recessive deafness), LOXHD1 (expressed in the mechanosensory hair cells in the inner ear, with mutations being associated with hearing defects) and GPR98 (G-protein coupled receptor 98, expressed in the central nervous system in humans and associated with Usher syndrome), all genes associated with diseases involved in human deafness. The gene reported to have the strongest evidence for accelerated evolution in the hominines is RNF213, a gene that in humans is associated with Moyamoya disease, where blood flow to the brain is restricted due to arterial stenosis. The paper reports "relatively similar" numbers of genes in humans (663), chimpanzees (562), and gorillas (535) that have apparently undergone accelerated evolution. In the gorilla, accelerated genes are enriched for developmental events in ear, hair follicle, gonad and brain development, and sensory perception of sound, with the most significantly accelerated gene in gorilla being EVPL, which encodes a component of the cornified envelope of keratinocytes. The authors speculate that this differential evolution "may be related to increased cornification of knuckle pads in gorilla."
The paper also reports instances of pairwise parallel evolution among hominines, with human and chimpanzee showing the largest numbers of paired genes, and with gorilla showing more parallel evolution with human than with chimpanzees. There were 84 instances of gene loss in gorilla due to the acquisition of a premature stop codon, and in "several" cases the gorilla genome encoded a single gene at a locus that in humans encodes a protein variant believed to cause inherited disease. The authors speculate that while the reason "variants that appear to cause disease in humans might be associated with a normal phenotype in gorillas is unknown" it is possible that there "are compensatory molecular changes elsewhere, or differing environmental conditions."
While the data relating to differences in gene transcription were not extensive or definitive, the paper reports that there is about a 7% divergence in splicing patterns between species for the genes examined.
The paper closes by reporting on genetic relationships between Gorilla gorilla (the western lowland gorilla) and Gorilla beringei (the eastern lowland gorilla). The data were consistent with the current disparity in population size between the eastern and western lowland gorilla populations; this evidence in the species DNA indicated that the disparity has existed for "many millennia" and thus is probably not the result of human predation and habitat invasion or disease occurrence such as "recent outbreaks of the Ebola virus." Even these results can be related to human-gorilla differences: gorillas were shown to have "greater copy number diversity" than humans, a result "consistent with previous observations in the great ape."
The authors state their conclusions best:
Since the middle Miocene -- an epoch of abundance and diversity for apes throughout Eurasia and Africa -- the prevailing pattern of ape evolution has been one of fragmentation and extinction. The present-day distribution of non-human great apes, existing only as endangered and subdivided populations in equatorial forest refugia, is a legacy of that process. Even humans, now spread around the world and occupying habitats previously inaccessible to any primate, bear the genetic legacy of past population crises. All other branches of the genus Homo have passed into extinction. It may be that in the condition of Gorilla, Pan and Pongo [orangutan] we see some echo of our own ancestors before the last 100,000 years, and perhaps a condition experienced many times over several million years of evolution. It is notable that species within at least three of these genera continued to exchange genetic material long after separation, a disposition that may have aided their survival in the face of diminishing numbers. As well as teaching us about human evolution, the study of the great apes connects us to a time when our existence was more tenuous, and in doing so, highlights the importance of protecting and conserving these remarkable species.
The work was performed by an international consortium of researchers working at the Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus; the Bioinformatics Research Center, Aarhus University; the Department of Genome Sciences, University of Washington School of Medicine; the European Bioinformatics Institute, Wellcome Trust Genome Campus; Department of Genetic Medicine and Development, University of Geneva Medical School; Institut de Biologia Evolutiva and Institucio Catalana de Recerca i Estudis Avançats, Barcelona; the Department of Zoology and Department of Oncology, Hutchison/MRC Research Centre, University of Cambridge; Cancer Research UK, Cambridge Research Institute; Howard Hughes Medical Institute, University of Washington; Institute of Medical Genetics, Cardiff University; Department of Anthropology, Yale University; The Genome Institute at Washington University, Washington University School of Medicine; MRC Functional Genomics Unit, University of Oxford, Department of Physiology, Anatomy and Genetics; Wellcome Trust Centre for Human Genetics, Oxford; Comparative Genomics Unit, Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health; Max Planck Institute for Evolutionary Anthropology, Primatology Department; Children's Hospital Oakland Research Institute; and the San Diego Zoo's Institute for Conservation Research.
Image of Western Lowland Gorilla at Bronx Zoo (above) by Fred Hsu, from the Wikipedia Commons under the Creative Commons license.
