Experimental Evaluation of a Direct Fitness Effect of the De Novo Evolved Mouse Gene Pldi.

De novo evolved genes emerge from random parts of noncoding sequences and have, therefore, no homologs from which a function could be inferred. While expression analysis and knockout experiments can provide insights into the function, they do not directly test whether the gene is beneficial for its carrier. Here, we have used a seminatural environment experiment to test the fitness of the previously identified de novo evolved mouse gene Pldi, which has been implicated to have a role in sperm differentiation. We used a knockout mouse strain for this gene and competed it against its parental wildtype strain for several generations of free reproduction. We found that the knockout (ko) allele frequency decreased consistently across three replicates of the experiment. Using an approximate Bayesian computation framework that simulated the data under a demographic scenario mimicking the experiment's demography, we could estimate a selection coefficient ranging between 0.21 and 0.61 for the wildtype allele compared to the ko allele in males, under various models. This implies a relatively strong selective advantage, which would fix the new gene in less than hundred generations after its emergence.

A humanized version of Foxp2 affects ultrasonic vocalization in adult female and male mice.

The transcription factor FoxP2 is involved in setting up the neuronal circuitry for vocal learning in mammals and birds and is thought to have played a special role in the evolution of human speech and language. It has been shown that an allele with a humanized version of the murine Foxp2 gene changes the ultrasonic vocalization of mouse pups compared to pups of the wild-type inbred strain. Here we tested if this humanized allele would also affect the ultrasonic vocalization of adult female and male mice. In a previous study, in which only male vocalization was considered and the mice were recorded under a restricted spatial and temporal regime, no difference in adult vocalization between genotypes was found. Here, we use a different test paradigm in which both female and male vocalizations are recorded in extended social contact. We found differences in temporal, spectral and syntactical parameters between the genotypes in both sexes, and between sexes. Mice carrying the humanized Foxp2 allele were using higher frequencies and more complex syllable types than mice of the corresponding wildtype inbred strain. Our results support the notion that the humanized Foxp2 allele has a differential effect on mouse ultrasonic vocalization. As mice carrying the humanized version of the Foxp2 gene show effects opposite to those of mice carrying disrupted or mutated alleles of this gene, we conclude that this mouse line represents an important model for the study of human speech and language evolution.

Cross-Species Single-Cell Analysis Reveals Divergence of the Primate Microglia Program.

Microglia, the brain-resident immune cells, are critically involved in many physiological and pathological brain processes, including neurodegeneration. Here we characterize microglia morphology and transcriptional programs across ten species spanning more than 450 million years of evolution. We find that microglia express a conserved core gene program of orthologous genes from rodents to humans, including ligands and receptors associated with interactions between glia and neurons. In most species, microglia show a single dominant transcriptional state, whereas human microglia display significant heterogeneity. In addition, we observed notable differences in several gene modules of rodents compared with primate microglia, including complement, phagocytic, and susceptibility genes to neurodegeneration, such as Alzheimer's and Parkinson's disease. Our study provides an essential resource of conserved and divergent microglia pathways across evolution, with important implications for future development of microglia-based therapies in humans.

Genomic resources for wild populations of the house mouse, Mus musculus and its close relative Mus spretus.

Wild populations of the house mouse (Mus musculus) represent the raw genetic material for the classical inbred strains in biomedical research and are a major model system for evolutionary biology. We provide whole genome sequencing data of individuals representing natural populations of M. m. domesticus (24 individuals from 3 populations), M. m. helgolandicus (3 individuals), M. m. musculus (22 individuals from 3 populations) and M. spretus (8 individuals from one population). We use a single pipeline to map and call variants for these individuals and also include 10 additional individuals of M. m. castaneus for which genomic data are publically available. In addition, RNAseq data were obtained from 10 tissues of up to eight adult individuals from each of the three M. m. domesticus populations for which genomic data were collected. Data and analyses are presented via tracks viewable in the UCSC or IGV genome browsers. We also provide information on available outbred stocks and instructions on how to keep them in the laboratory.

Communication at the Garden Fence--Context Dependent Vocalization in Female House Mice.

House mice (Mus musculus) live in social groups where they frequently interact with conspecifics, thus communication (e.g. chemical and/or auditory) is essential. It is commonly known that male and female mice produce complex vocalizations in the ultrasonic range (USV) that remind of high-pitched birdsong (so called mouse song) which is mainly used in social interactions. Earlier studies suggest that mice use their USVs for mate attraction and mate choice, but they could also be used as signal during hierarchy establishment and familiarization, or other communication purposes. In this study we elucidated the vocalization behaviour of interacting female mice over an extended period of time under semi-natural conditions. We asked, if the rate or structure of female vocalization differs between different social and non-social contexts. We found that female USV is mainly used in social contexts, driven by direct communication to an unknown individual, the rate of which is decreased over time by a familiarization process. In addition we could show that female mice use two distinct types of USVs, differing in their frequency, which they use differently depending on whether they directly or indirectly communicate with another female. This supports the notion that vocalization in mice is context dependent, driven by a reasonable and yet underestimated amount of complexity that also involves the interplay between different sensory signals, like chemical and auditory cues.

A role for ultrasonic vocalisation in social communication and divergence of natural populations of the house mouse (Mus musculus domesticus).

It has long been known that rodents emit signals in the ultrasonic range, but their role in social communication and mating is still under active exploration. While inbred strains of house mice have emerged as a favourite model to study ultrasonic vocalisation (USV) patterns, studies in wild animals and natural situations are still rare. We focus here on two wild derived mouse populations. We recorded them in dyadic encounters for extended periods of time to assess possible roles of USVs and their divergence between allopatric populations. We have analysed song frequency and duration, as well as spectral features of songs and syllables. We show that the populations have indeed diverged in several of these aspects and that USV patterns emitted in a mating context differ from those emitted in same sex encounters. We find that females vocalize not less, in encounters with another female even more than males. This implies that the current focus of USVs being emitted mainly by males within the mating context needs to be reconsidered. Using a statistical syntax analysis we find complex temporal sequencing patterns that could suggest that the syntax conveys meaningful information to the receivers. We conclude that wild mice use USV for complex social interactions and that USV patterns can diverge fast between populations.