Australia: The Land Where Time Began
Gorilla Genome Sequence – Insights into Hominid Evolution
According to Scally et al. Gorillas are the closet living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. In this paper they present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the entire genomes of all extant great ape genera. They proposed a synthesis of genetic and fossil evidence that was consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 Million years ago (Ma). Gorilla is closer to human or chimpanzee than the latter are to each other; but it is rarer around coding genes, which indicates pervasive selection throughout the evolution of great apes, and the functional consequences in gene expression. It was revealed by a comparison of coding genes that approximately 500 genes displayed accelerated evolution on each of the lineages, gorilla, human and chimpanzee, and there is evidence for parallel acceleration, especially for genes that are involved in hearing. Western and eastern species of gorilla were also compared, and it was estimated that the average sequence divergence time as 1.75 Ma, though with evidence of more recent genetic exchange and a population bottleneck in the eastern species. A greater understanding of great ape evolution and biology will be promoted by the use of genome sequence in these as well as future analyses.
Many elements of anatomy and physiology are shared between humans with gorillas and chimpanzees, the similarity of humans to these species was emphasised by Darwin and Huxley in the first evolutionary accounts of human origins (Huxley, 1863). It was confirmed by molecular studies that we are closer to the African apes than to orang-utans and on average closer to chimpanzees than to gorillas (King & Wilson, 1975). There are functional differences between the great apes and their relevance to human evolution, which have been assisted by reference genome sequences for chimpanzee (Chimpanzee Sequencing and Analysis Consortium, 2005) and orang-utan (Locke et al., 2011), have been explored by subsequent analyses (Locke et al., 2011). In this paper Scally et al. have provided reference assembly and initial analysis for the gorilla genome sequence, which establishes a foundation for future study of the great ape evolution and genetics. The costs of sequencing have been substantially reduced by recent technological development, though the assembly of whole vertebrate genomes has remained a challenging computational problem. They used a single female western gorilla (Gorilla gorilla gorilla) named Kamilah to generate a reference assembly, using 5.4 x 109 base pairs (5.4 Bbp) of capillary sequence combined with 166.8 Gdp of illumine read pairs. Genes, transcripts and predictions of gene orthologues and paralogues were annotated by Ensembl (Hubbard et al., 2009), and evidence that was found by additional analysis for 498 functional long (>200 bp) intergenic RNA transcripts. It was found by an assessment of assembly quality using finishing fosmid sequences that a typical (N50) of error free sequence are 7.2 kbp long, that have errors clustered in repetitive regions. The total rate of single base and indel errors is 0.13 kbp, outside repeat masked regions and away from contig ends. In order to enable a comparison of species within the Gorilla genus, Scally et al. also collected less extensive sequence data for 3 other gorillas. At present gorillas are found only within several isolated and endangered populations whose evolutionary relationships are uncertain. As well as Kamilah the analysis of Scally et al. included 2 western lowland gorillas, Kwanza (male) and EB(JC) (female) and 1 eastern lowland gorilla, Mukisi (male).
Speciation of the great apes
In this study the Kamilah assembly was included with human, chimpanzee (Pan troglodytes) orang-utan (Pongo abelii) and macaque (Macaca mulatta) I a 5-way whole-genome alignment using the Ensembl EPO pipeline (Paten et al., 2008). When low quality regions of the chimpanzee assembly and regions with many alignment gaps were filtered out, the results obtained was 2.01 Gdp of 1:1:1:1 orthologous alignment blocks to which were then applied a coalescence inference model, CoalHMM, in order to estimate the timescales and population sizes involved in the speciation of hominins with orang-utan as an out-group.
In the interpretation of the results from CoalHMM there are 2 issues that need to be addressed.
1) The results themselves are obtained in units of sequence divergence rather than years, and therefore need to be scaled by an appropriate yearly mutation rate.
2) CoalHMM makes several simplifying assumptions, as does any model, the consequences of which need to be understood in the context of realistic demography. These issues were discussed in turn.
The results of CoalHMM would correspond to speciation time estimates THC (for human-chimpanzee) and THCG (for human-chimpanzee-gorilla) of 3.7 and 5.95 Ma, respectively, using a rate of 10-9 mutations/bp/year derived from human-macaque sequence divergence and as used as in previous calculations. These dates are consistent with other recent molecular estimates (Bradley, 2008; Burgess & Yang, 2008), though they are at variance with certain aspects of the fossil record, which includes several fossils which have been proposed, though not accepted universally (Wood & Harrison, 2011), to be hominins, and therefore to post-date the human-chimpanzee split. The relationship between molecular and fossil evidence has indeed remained difficult to resolve in spite of the accumulation of genetic data (Steiper & Young, 2008). Direct estimates of mutation rate per generation in population of modern humans, based on the incidence of disease-causing mutations (Lynch, 2010) or sequencing of familial trios (The 1000 Genome Project Consortium, 2011; 2011; Roach et al., 2010), indicate that a lower value of (0.5 to 0.6) x 10-9 bp/year is plausible, based on average hominine generation times of 20-25 years. This would give estimates of about 6 and 10 Ma for THC and THCG, potentially in better agreement with the fossil record.
This timetable for hominine speciation must, however, also be reconciled with older events, such as the speciation of orang-utan, which is believed to have occurred no earlier than the Middle Miocene (12-16 Ma), as prior to this, fossil apes differed substantially from what might be expected for an early great ape (Hartwig et al., 2002). If the changing of mutation rates over time is allowed for this becomes possible, with a mutation rate of 1 x 10-9 bp/year in the common ancestor of great apes, which decreases to lower values in all extant species. Comparable changes in rate of mutations have been observed previously in primate evolution on larger timescales, including a branch length of decrease of about 30% in humans compared to baboons since their common ancestor (Kim et al., 2006). Within the great apes a decrease is also a predicted consequence of the increase in body sizes that has been observed over this period of time and the associated small size with shorter generation times in other primates (Fleagle et al., 1998), is consistent with deviations from the molecular clock that are seen in sequence divergence of the great apes and macaque. It was noted by Scally et al., however, that Sahelanthropus and Chororapithecus have remained difficult to incorporate in this model, and can be in hominin and gorilla genera only if most of the decrease occurred early in the evolution of the great apes.
That ancestral demography may have affected the genetic inferences is an alternative explanation for the discrepancy that is apparent in fossil and genetic dates (if the issue of whether or not the fossil taxa have been placed correctly). Certainly CoalHMM’s model does not fit the model in all respects. Possibly of most importance, it assumes that the ancestral population sizes are constant in time, and that there was no gene flow between populations that were separated, approximations that may not hold in reality. It is suggested by simulations that an ancestral population would have had limited impact on the inference of THC on the ancestral population bottleneck, its influence having been largely captured by changes in the effective population size of the model. The speciation time that is estimated by CoalHMM represents an average that is weighted by gene flow over the period of separation, under conditions of genetic exchange between populations following the main separation of the Chimpanzee and human lineages. In some cases this can mean that it can be substantially older than the most recent exchange. It would, however, be more recent than the speciation time inferred from fossils if there had been strong gene flow between populations following the development of derived fossil characteristics. E.g., for the extent that this is plausible as part of a non-allopatric speciation process, it constitutes an alternative explanation for the discrepancy of the data while not requiring a change in mutation rate.
The inability to observe mutation rates in the past means that the timing of events from genetic data has remained uncertain, though whole-genome comparisons can be strongly conclusive about the ordering of speciation events. Scally et al. state that in their view possible variation in mutation rates allows hominid genomic data to be consistent with values of THC from 5.5 Ma to 7 Ma and THCG from 8.5 Ma to 12 Ma with the potential of ancestral demographic structure adding inherent ambiguity to both events. Better resolution may be provided by further integrated analysis of fossil and genetic evidence.
The prevailing pattern of ape evolution has been one of fragmentation and extinction (Begun, 2007), since the Middle Miocene which was an epoch of abundance and diversity for apes throughout Eurasia and Africa. The distribution at the present of non-human great apes, which exist only as endangered and subdivided populations in equatorial forest refugia (The IUCN Red List of Threatened Species. Version, 2010. 1, 2010), is a legacy of that process. Even humans, that are now spread around the world and occupying habitats that were previously inaccessible to any primate, bear the genetic legacy of past population crises. All other branches of the Homo genus have gone extinct. Scally et al. suggest it may be that we see some echo of our own ancestors prior to the last 100,000 years in the condition of Gorilla, Pan and Pongo, and possibly a condition experienced many times over several million years of evolution. It is notable that species of at least these genera continued to exchange genetic material long after separation (Locke et al., 2011; Green et al., 2010), a deposition that may have aided their survival in the face of diminishing numbers. As well as teaching about human evolution, the study of the great apes connects us to a time when our own existence was more tenuous, and in doing so, highlights the importance of protecting and conserving these remarkable species.
Scally, A., et al. (2012). "Insights into hominid evolution from the gorilla genome sequence." Nature 483(7388): 169-175.
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