Contrasts between adaptive coding and noncoding changes during human evolution

Abstract

Changes in non-protein-coding regulatory DNA sequences have been proposed to play distinctive roles in adaptive evolution. We analyzed correlations between gene functions and evidence for positive selection in a common statistical framework across several large surveys of coding and noncoding sequences throughout the human genome. Strong correlations with both classifications in gene ontologies and measurements of gene expression indicate that neural development and function have adapted mainly through noncoding changes. In contrast, adaptation via coding changes is dominated by immunity, olfaction, and male reproduction. Genes with highly tissue-specific expression have undergone more adaptive coding changes, suggesting that pleiotropic constraints inhibit such changes in broadly expressed genes. In contrast, adaptive noncoding changes do not exhibit this pattern. Our findings underscore the probable importance of noncoding changes in the evolution of human traits, particularly cognitive traits.adaptive evolution | human origins | protein-coding DNA sequences | noncoding DNA sequences | regulatory DNA sequences A mong the most fundamental unanswered questions about adaptive evolution are whether it proceeds primarily through changes in protein-coding DNA sequences or noncoding regulatory sequences, whether the proportions of coding and noncoding changes vary appreciably among organismal traits, and, if so, why (1, 2). For example, it has been argued that morphological adaptation occurs mainly via noncoding changes, on the grounds that many genes underlying development are active in many contexts, and a noncoding mutation is likely to alter a gene's activity in only one or a few contexts, avoiding pleiotropic constraints (3-5). These questions have been addressed mainly using case studies of individual genes and traits; however, they now can be addressed on a genomic scale, and doing so is indispensable for assessing whether consistent, intelligible patterns exist.The human genome is especially suitable for such inquiry, for two reasons. First, there are now many surveys aiming to detect signatures of positive selection on sequences throughout the human genome (6), most focusing on coding sequences but a few focusing on noncoding sequences. Second, the extensive functional annotations of the human genome often make it possible to infer something about the trait through which positive selection on a sequence arose (6). Here we evaluate what several large surveys of the human genome imply about the roles of coding and noncoding changes in adaptive evolution, how these roles vary among gene functions, and what this variation suggests about its causes.In this work, we analyzed three surveys of coding sequences (7-9) and three surveys of noncoding sequences (10-12) (Methods and Table S1). Each survey aims to detect a signature of positive selection, distinguishes selection on coding versus noncoding sequences, and treats thousands of sequences without a priori bias regarding function. The surveys' data are diverse, a...

LINC00507 Is Specifically Expressed in the Primate Cortex and Has Age-Dependent Expression Patterns

“…It is thought that one of the major evolutionary drivers of the complexity of the human brain is the non-coding transcriptome (Haygood et al 2010). Indeed, the human brain and, in particular, the frontal cortex, appears to be a rich source of lincRNAs (Mills et al 2013).…”

Understanding LiP Promoters from Phanerochaete chrysosporium: A Bioinformatic Analysis

“…Also, recent analyses of the human genome suggest a distinctive role for adaptative changes both in coding and non-coding sequences. Changes in non-coding sequences appear primarily related to changes in neural development (Haygood et al, 2010). The last decade has witnessed an explosion of studies showing that the complex regulation of gene expression is mainly modulated by the manifold interactions between transcription factors (TFs) with their corresponding transcription factors binding sites (TFBSs) on DNA (Wei & Yu, 2007).…”

“…One of the most fundamental and unanswered questions is whether adaptative evolution proceeds through changes in protein-coding DNA sequences or through non-coding regulatory sequences. It has been argued that morphological change occurs mainly via non-coding changes (Haygood et al, 2010). Diptera studies showed that cis-regulatory sequences that control transcription are a common source of divergent protein expression patterns and thus of phenotypic change (Wittkopp, 2006).…”

Seleção balanceadora no genoma humano: relevância biológica e consequências deletérias

“…Graças à grande quantidade de scans genômicos em busca de assinaturas de seleção positiva, sabe-se hoje que muitos dos genes com tais assinaturas estão relacionados com certas categorias: "imunidade e defesa", "percepção sensorial" e "imunidade mediada por células T", "gametogênese", "espermatogênese e mobilidade" (Harris e Meyer, 2006;Nielsen et al, 2005). Para as regiões não-codificadoras, destacam-se processos biológicos como "neurogênese", "outras atividades neuronais" e "desenvolvimento muscular" (Haygood et al, 2010).…”