Orthologues, Paralogues and Horizontal Gene Transfer in the Human Holobiont

Abstract

Abstract Evolution is commonly measured using comparative phylogenetic analysis. Comparisons of orthologous characters and sequences from different species are used to infer organismal evolution. Analyses of duplicated genes can be used to root phylogenetic trees and infer ancestral groups. The expansion of gene families through gene and genome duplications allowed more complex regulatory and developmental pathways to evolve in multicellular eukaryotes. In prokaryotes and single‐celled eukaryotes, the acquisition of foreign genes by horizontal gene transfer is the main mechanism for gene family expansion; it allows genomes to evolve new traits quickly and facilitates the assembly of new metabolic pathways. Additionally, prokaryotic organisms with short generation times will accumulate genetic adaptations at a much faster rate than organisms with longer generation times (e.g. humans). In multicellular animals where somatic cells and gametes are separate, acquisition of foreign genes is rare, leading to high levels of similarity in gene content. However, multicellular eukaryotes have evolved in close association with prokaryotic symbionts that impact development, physiology and ecology of the association. To understand the evolution of the complex human systems, we must consider the genomes of the associated microbiota, known as the microbiome. We must therefore consider the human as a holobiont, a complex ecosystem, whose evolutionary fitness is determined by the host, the symbionts and their interactions. Key Concepts: Orthologous structures or sequences in two organisms are homologues that evolved from the same feature in their last common ancestor; orthologues reflect organismal evolution. Paralogues are homologues whose evolution reflects gene duplication events. Genomes can evolve by acquiring genes through horizontal gene transfer or from the fusion of complete genomes through symbiosis. Individual humans can differ slightly in genome content with variation related primarily to deletions or regions of segmental duplication. Apparent differences in complexity between species may be due to a varying amount of noncoding regulatory sequence, regulating a fairly stable core of protein‐coding genes. Repeated sequences derived from transposable elements comprise a large portion of the genome and can have a significant role in gene duplication through the formation of pseudogenes that lack introns. Duplicated segments in the human genome are generally enriched in protein coding genes and have the potential to evolve novel transcripts, either as whole‐gene duplications or through the creation of mosaic genes. Variations in the number of paralogues in humans reveal genomic regions under selective pressures. Orthologous regions amongst genomes are found in both protein coding exons and noncoding regions of the genome. Rapidly evolving regions of the human genome include intergenic regions that may be important for gene regulation. Humans can be viewed as a holobiont, a complex ecosystem whose evolutionary fitness is determined by interactions of the host and microbiota. The microbiome, the sum of microbial genomes carried in our symbionts, encode metabolic capacities that we have not had to evolve in our nuclear genome.