A Scan for Positively Selected Genes in the Genomes of Humans and Chimpanzees

By Rasmus Nielsen, Carlos D. Bustamante, Andrew G. Clark, S. Glanowski, Timothy B Sackton, Melissa J. Hubisz, A. Fledel-Alon, D. Tanenbaum, D. Civello, T. White and 3 more. PLoS Biology, 2005

972 citations recorded by the source corpus.

Since the divergence of humans and chimpanzees about 5 million years ago, these species have undergone a remarkable evolution with drastic divergence in anatomy and cognitive abilities. At the molecular level, despite the small overall magnitude of DNA sequence divergence, we might expect such evolutionary changes to leave a noticeable signature throughout the genome. We here compare 13,731 annotated genes from humans to their chimpanzee orthologs to identify genes that show evidence of positive selection. Many of the genes that present a signature of positive selection tend to be involved in sensory perception or immune defenses. However, the group of genes that show the strongest evidence for positive selection also includes a surprising number of genes involved in tumor suppression and apoptosis, and of genes involved in spermatogenesis. We hypothesize that positive selection in some of these genes may be driven by genomic conflict due to apoptosis during spermatogenesis. Genes with maximal expression in the brain show little or no evidence for positive selection, while genes with maximal expression in the testis tend to be enriched with positively selected genes. Genes on the X chromosome also tend to show an elevated tendency for positive selection. We also present polymorphism data from 20 Caucasian Americans and 19 African Americans for the 50 annotated genes showing the strongest evidence for positive selection. The polymorphism analysis further supports the presence of positive selection in these genes by showing an excess of high-frequency derived nonsynonymous mutations.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/9bdbfbbe4d2bae9625d9b69d8b333df5631580b7

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Citations in the corpus

Molecular signatures of natural selection. (2005, background): “Other examples include genes involved in gametogenesis or expressed on the surface of gametes ( 75 , 109, 110, 122).”
Comparing the human and chimpanzee genomes: Searching for needles in a haystack (2005, background): “Genes that have the signature of accelerated evolution (Clark et al. 2003; Nielsen et al. 2005), i.”
Natural selection on protein-coding genes in the human genome (2005, neutral): “00211 31 37 (18) 343 (207) RNA helicase 0.”
A Map of Recent Positive Selection in the Human Genome (2006, background): “These types of processes have been identified as targets of selection in previous studies of human-chimpanzee divergence [10,11].”
PAML 4: phylogenetic analysis by maximum likelihood. (2007, background): “For example, both evolutionary conservation indicating negative purifying selection and accelerated evolution driven by positive Darwinian selection have been employed to detect functionally significant regions of the genome (e.g., Thomas et al. 2003; Nielsen et al. 2005; Sawyer et al. 2005).”
A Genome-Scan Method to Identify Selected Loci Appropriate for Both Dominant and Codominant Markers: A Bayesian Perspective (2008, background): “A wide variety of methods have been developed to identify regions of the genome that have been subject to natural selection (see Nielsen et al. 2005, for a review).”
Supervised Machine Learning for Population Genetics: A New Paradigm (2018, methodology): “…of these studies [13] used a SVM to combine the ω statistic of Kim and Nielsen (which measures the spatial pattern of LD expected around a sweep [38]) with composite-likelihood ratio of Nielsen et al. (also known as CLR, which highlights the spatial skew in the SFS expected around a sweep [49]).”
γ-MYN: a new algorithm for estimating Ka and Ks with consideration of variable substitution rates (2009, methodology): “To overcome the weakness, there have been methods developed, such as Likelihood Ratio Test (LRT) [53-56] implemented in PAML [57] and Hyphy software [58], to identify positive selection [45,59-61], which tend to be qualitative.”
Comparative Genomics (2007, positive): “As was the case for human-mouse comparisons discussed above, the KA/KS ratio was computed in genome-wide comparison of the human and chimpanzee gene sets (Clark et al. 2003; Bustamante et al. 2005; Chimpanzee Sequencing and Analysis Consortium 2005; Nielsen et al. 2005).”
Detecting Individual Sites Subject to Episodic Diversifying Selection (2012, background): “only 35=8079 were found in a human - chimpanzee genome-wide comparison [9].”
THE LOCUS OF EVOLUTION: EVO DEVO AND THE GENETICS OF ADAPTATION (2007, background): “Those who feel otherwise would do well to remember Carl Sagan‘s (1987, p. 45) testy remark when pressed to give an opinion about the probability of extraterrestrial intelligence: “Really, it’s okay to reserve judgment until the evidence is in.””
A census of human transcription factors: function, expression and evolution (2009, background): “Support for this opinion has increased recently, as comparative surveys of primate genomes have failed to reveal dramatic differences among genes that mediate the most distinguishing traits, such as cognitive, behavioural and dietary processe”