Gene Duplication and Protein Evolution in Tick-Host Interactions

Abstract

Ticks modulate their hosts' defense responses by secreting a biopharmacopiea of hundreds to thousands of proteins and bioactive chemicals into the feeding site (tick-host interface). These molecules and their functions evolved over millions of years as ticks adapted to blood-feeding, tick lineages diverged, and host-shifts occurred. The evolution of new proteins with new functions is mainly dependent on gene duplication events. Central questions around this are the rates of gene duplication, when they occurred and how new functions evolve after gene duplication. The current review investigates these questions in the light of tick biology and considers the possibilities of ancient genome duplication, lineage specific expansion events, and the role that positive selection played in the evolution of tick protein function. It contrasts current views in tick biology regarding adaptive evolution with the more general view that neutral evolution may account for the majority of biological innovations observed in ticks.

Keywords: blood-feeding evolution; gene duplication; hematophagy; protein family evolution; salivary gland; tick evolution.

Figure 1

Gene duplication in the evolution of blood-feeding in ticks. The four main stages in the evolution of blood-feeding includes host detection, host attachment, tick-host interaction, and blood meal processing (Mans, 2014). Tick salivary glands play a central role in tick-host interactions by secreting the bioactive molecules that modulates host defense mechanisms. Some of these secreted proteins belong to large protein families expanded by gene duplication that can count from tens to hundreds of different genes per tick species. BPTI (Basic pancreatic trypsin inhibitor), BTSP (Basic tail secretory proteins), LTB4 (leukotriene B4), LTC4 (leukotriene C4), TXA2 (thromboxane A2). Information on protein families summarized from Mans et al. (2016).

Figure 2

Models of gene duplication and evolution of function. Indicated are various models for the evolution of function before and after gene duplication events. Gene dosage refers to maintenance of gene duplicates with the same function. Neofunctionalization refers to the acquisition of a new function and loss of the old function in one gene duplicate. Subfunctionalization refers to the segregation of two functions in different gene duplicates that was present in the ancestral gene. Multifunctionalization refers to acquisition of a new function in one gene copy, while retaining the original function. Escape from adaptive conflict refers to an ancestral gene with functions that are overlapping or sub-functional due to exclusion effects. These functions are optimized in respective gene duplicates after duplication. Adaptive radiation refers to ancestral genes that have pre-adapted functions, which allow the evolution of similar functions in gene duplicates. Permanent heterozygote refers to heterozygotes that have better fitness than homozygotes and where gene duplication leads to fixation of both alleles in paralogs. Multi-allelic diversification refers to the case where the highest number of heterozygous individuals in a population is advantageous. Gene duplications leads to many divergent genes coding for the same function.

Figure 3

Evolutionary scenarios in the reconstruction of biogenic amine binding function. Indicated are the phylogenetic relationships of various tick genera as determined with mitochondrial analysis (Mans et al., 2012). Terminal nodes represent extant lipocalins for which empirical histamine or serotonin binding data exist. The number of lipocalins for which experimental data have been generated are indicated as cups (lipocalin~calyx~cup) that bind histamine in the upper binding site and serotonin and/or histamine in the lower binding pocket. Names of characterized lipocalins are indicated below their genus names. Internal nodes represent two possible ancestral binding site hypotheses: (A) The ancestral BABP had a single lower serotonin-binding site, or (B) the ancestral BABP had an upper histamine and lower histamine/serotonin-binding site.