New Genes and Functional Innovation in Mammals

Abstract

The birth of genes that encode new protein sequences is a major source of evolutionary innovation. However, we still understand relatively little about how these genes come into being and which functions they are selected for. To address these questions, we have obtained a large collection of mammalian-specific gene families that lack homologues in other eukaryotic groups. We have combined gene annotations and de novo transcript assemblies from 30 different mammalian species, obtaining ∼6,000 gene families. In general, the proteins in mammalian-specific gene families tend to be short and depleted in aromatic and negatively charged residues. Proteins which arose early in mammalian evolution include milk and skin polypeptides, immune response components, and proteins involved in reproduction. In contrast, the functions of proteins which have a more recent origin remain largely unknown, despite the fact that these proteins also have extensive proteomics support. We identify several previously described cases of genes originated de novo from noncoding genomic regions, supporting the idea that this mechanism frequently underlies the evolution of new protein-coding genes in mammals. Finally, we show that most young mammalian genes are preferentially expressed in testis, suggesting that sexual selection plays an important role in the emergence of new functional genes.

Translation of neutrally evolving peptides provides a basis for de novo gene evolution

“…For a protein to have proteomics evidence, we required at least two distinct perfect matches of peptides that did not map to any other protein in the dataset, allowing for up to two mismatches. Under these conditions the false positive rate was estimated to be below 0.2% in a previous study 50 . The estimation was based on the results obtained for ORFs in which the amino acid sequence was randomized and for ORFs in intronic sequences.…”

“…We excluded lncRNAs that overlapped annotated pseudogenes or that showed significant sequence similarity to known protein-coding sequences (BLASTP, e-value < -4 ). In the case of rat we employed a previously generated transcript assembly 50 .…”

“…(limited to one strand, e-value < 10 -4 ) . We also performed sequence similarity searches against the annotated proteomes of mammalian-species and 34 non-mammalian eukaryotes from a diverse range of groups compiled in a previous study 50 , using BLASTP (e-value < -4 ).…”

Signaling Enzymes Required for Sperm Maturation and Fertilization in Mammals

“…Several predominantly testis-expressed proteins present in mammalian sperm have been identified as mammal-specific. These include proteins involved in DNA binding, sperm egg binding or those required for required for the unique structural features of mammalian sperm, such as protamine 3, SMCP, and ADAM proteins (Cho, 2012;Luis Villanueva-Canas et al, 2017). However, the observation that the four signaling enzymes suggested to be mechanistically interrelated are mammal specific isoforms is significant, suggesting a unique function in male gametes (Figure 3C).…”

That is life: communicating RNA networks from viruses and cells in continuous interaction

“…This means that any RNA group transcribed out of the DNA storage medium may play a new, modular, unexpected role in cooperating or competing RNAs, genetic regulations, counter‐regulations, and diseases or infection events. Such noncoding RNAs most often derive from mobile genetic elements and are the major contributors to regulatory ncRNAs, which include endogenous retroviruses, their defective derivatives, and other persistent genetic parasites (not forgetting their degraded parts) …”